Name (Synonyms) | Correlation | |
---|---|---|
drug505 | Hydroxychloroquine Wiki | 0.27 |
drug850 | Placebo Wiki | 0.18 |
drug865 | Placebo oral tablet Wiki | 0.17 |
drug108 | Azithromycin Wiki | 0.14 |
drug957 | Remdesivir Wiki | 0.13 |
drug522 | Hydroxychloroquine Sulfate Wiki | 0.13 |
drug1062 | Standard of Care Wiki | 0.13 |
drug431 | Favipiravir Wiki | 0.11 |
drug650 | Losartan Wiki | 0.11 |
drug60 | Anakinra Wiki | 0.11 |
drug874 | Plasma Wiki | 0.10 |
drug762 | No intervention Wiki | 0.10 |
drug1230 | Vitamin C Wiki | 0.10 |
drug872 | Placebos Wiki | 0.09 |
drug83 | Ascorbic Acid Wiki | 0.09 |
drug1231 | Vitamin D Wiki | 0.09 |
drug239 | Camostat Mesilate Wiki | 0.09 |
drug958 | Remdesivir placebo Wiki | 0.08 |
drug510 | Hydroxychloroquine + azithromycin Wiki | 0.08 |
drug516 | Hydroxychloroquine - Weekly Dosing Wiki | 0.08 |
drug775 | Normal saline Wiki | 0.08 |
drug645 | Lopinavir-Ritonavir Wiki | 0.08 |
drug1422 | vv-ECMO only (no cytokine adsorption) Wiki | 0.08 |
drug1397 | standard care Wiki | 0.08 |
drug905 | Prone positioning Wiki | 0.08 |
drug761 | No Intervention Wiki | 0.08 |
drug976 | Routine care for COVID-19 patients Wiki | 0.08 |
drug978 | Ruxolitinib Oral Tablet Wiki | 0.08 |
drug467 | HB-adMSCs Wiki | 0.08 |
drug1258 | Zinc Sulfate Wiki | 0.08 |
drug1020 | Selinexor Wiki | 0.08 |
drug1421 | vv-ECMO + cytokine adsorption (Cytosorb adsorber) Wiki | 0.08 |
drug828 | Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances Wiki | 0.08 |
drug1036 | Single Dose of Hydroxychloroquine Wiki | 0.08 |
drug286 | Colchicine Wiki | 0.08 |
drug923 | Questionnaire Wiki | 0.08 |
drug647 | Lopinavir/ritonavir Wiki | 0.07 |
drug122 | BCG Vaccine Wiki | 0.07 |
drug1255 | Zinc Wiki | 0.07 |
drug755 | Nitric Oxide Wiki | 0.07 |
drug637 | Lopinavir / Ritonavir Wiki | 0.07 |
drug757 | Nitric Oxide Gas Wiki | 0.07 |
drug527 | Hydroxychloroquine Sulfate 200 MG [Plaquenil] Wiki | 0.07 |
drug1278 | blood sample Wiki | 0.07 |
drug586 | Interferon Beta-1A Wiki | 0.07 |
drug1168 | Tocilizumab Wiki | 0.07 |
drug977 | Ruxolitinib Wiki | 0.07 |
drug262 | Chloroquine Wiki | 0.07 |
drug513 | Hydroxychloroquine + placebo Wiki | 0.06 |
drug1390 | samling of oropharynx and nasopharynx Wiki | 0.06 |
drug880 | Pleth variability index Wiki | 0.06 |
drug1338 | measurement of circulating sFlt1 concentration Wiki | 0.06 |
drug103 | Awake Prone Positioning Wiki | 0.06 |
drug1004 | Saline Control Wiki | 0.06 |
drug889 | Povidone-Iodine 0.5% Wiki | 0.06 |
drug807 | Oxygen Therapy Wiki | 0.06 |
drug528 | Hydroxychloroquine Sulfate 200 milligram (mg) Tab Wiki | 0.06 |
drug934 | REGN3051 Wiki | 0.06 |
drug495 | Hospital anxiety and depression scale Wiki | 0.06 |
drug1322 | iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System Wiki | 0.06 |
drug590 | Interferon-Beta Wiki | 0.06 |
drug118 | BAT Wiki | 0.06 |
drug497 | Human Biological samples Wiki | 0.06 |
drug610 | Isotretinoin Only Product in Oral Dose Form Wiki | 0.06 |
drug1173 | Toraymyxin PMX-20R (PMX Cartridge) Wiki | 0.06 |
drug56 | Alvelestat (MPH996) Plus Aerosolized 13 cis retinoic acid Wiki | 0.06 |
drug754 | Nitazoxanide Tablets Wiki | 0.06 |
drug1106 | Survey Wiki | 0.06 |
drug926 | Questionnaire with precaution information Wiki | 0.06 |
drug1204 | Umbilical Cord Mesenchymal Stem Cells Wiki | 0.06 |
drug1107 | Survey and Questionnaire Wiki | 0.06 |
drug84 | Ascorbic Acid and Zinc Gluconate Wiki | 0.06 |
drug1234 | VivaDiag™ COVID-19 lgM/IgG Rapid Test Wiki | 0.06 |
drug311 | Convalescent Plasma 1 Unit Wiki | 0.06 |
drug1264 | allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC) Wiki | 0.06 |
drug1182 | Treatment group: will receive a combination of Nitazoxanide, Ribavirin and Ivermectin for a duration of seven days : Wiki | 0.06 |
drug342 | Dapagliflozin Wiki | 0.06 |
drug699 | Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF) Wiki | 0.06 |
drug447 | Follow-up at 14 days Wiki | 0.06 |
drug562 | Ibuprofen Wiki | 0.06 |
drug273 | Clarithromycin Wiki | 0.06 |
drug788 | Odd/Even birth year intervention groups Wiki | 0.06 |
drug1364 | oral nutrition supplement (ONS) enriched in eicosapentaenoic acid, gamma-linolenic acid and antioxidants Wiki | 0.06 |
drug1223 | Verapamil Wiki | 0.06 |
drug477 | Halo Oral Spray Wiki | 0.06 |
drug1327 | isocaloric/isonutrigenous ONS Wiki | 0.06 |
drug783 | Observational Study Wiki | 0.06 |
drug1237 | WHO recommendations (waiting condition) Wiki | 0.06 |
drug448 | Fondaparinux Wiki | 0.06 |
drug606 | Intravenous saline injection (Placebo) Wiki | 0.06 |
drug73 | Anti-Sars-CoV-2 Convalescent Plasma Wiki | 0.06 |
drug993 | SARS-CoV-2-test Wiki | 0.06 |
drug427 | Extra blood sample Wiki | 0.06 |
drug935 | RIA-device (Remote Investigation and Assessment) Wiki | 0.06 |
drug1288 | conjunctival RT PCR Wiki | 0.06 |
drug172 | Blood donation from convalescent donor Wiki | 0.06 |
drug904 | Prone position ventilation Wiki | 0.06 |
drug844 | Physical Therapy Wiki | 0.06 |
drug72 | Anti-SARS-CoV2 Serology Wiki | 0.06 |
drug476 | HOME-CoV rule implementation Wiki | 0.06 |
drug652 | Low Dose Radiotherapy Wiki | 0.06 |
drug1240 | Web Based Survey Wiki | 0.06 |
drug41 | Additional biological samples Wiki | 0.06 |
drug577 | Inhaled Hypertonic ibuprofen Wiki | 0.06 |
drug940 | Ramipril 2.5 MG Oral Capsule Wiki | 0.06 |
drug383 | Duplex ultrasound and Computed Tomography Angiography Wiki | 0.06 |
drug1090 | Sterile Normal Saline for Intravenous Use Wiki | 0.06 |
drug994 | SARS-CoV2 serum antibody testing Wiki | 0.06 |
drug57 | Ambrisentan Wiki | 0.06 |
drug728 | NO intervention planned due to the observational study design - only a diagnostic testing Wiki | 0.06 |
drug423 | Experimental: Questionnaire without precaution information Wiki | 0.06 |
drug690 | Melatonin 2mg Wiki | 0.06 |
drug657 | Low-dose Chest CT Wiki | 0.06 |
drug6 | 0.9%NaCl Wiki | 0.06 |
drug1023 | Serologic SARS-CoV-2 screening Wiki | 0.06 |
drug489 | High Flow Nasal Oxygen (HFNO) Wiki | 0.06 |
drug81 | ArtemiC Wiki | 0.06 |
drug819 | PTSD Wiki | 0.06 |
drug1124 | Taste and olfactory function evaluation Wiki | 0.06 |
drug676 | Mannitol Wiki | 0.06 |
drug1407 | survey Wiki | 0.06 |
drug617 | Kerecis Oral and Nasal Spray Wiki | 0.06 |
drug933 | REGN3048 Wiki | 0.06 |
drug1005 | Saline Nasal Irrigation Wiki | 0.06 |
drug1178 | Transfusion of SARS-CoV-2 Convalescent Plasma. Wiki | 0.06 |
drug1265 | alpha one antitrypsin inhalation Wiki | 0.06 |
drug558 | INO-4800 Wiki | 0.06 |
drug317 | Convalescent anti-SARS-CoV-2 plasma Wiki | 0.06 |
drug472 | HCQ + Placebo Wiki | 0.06 |
drug985 | SARS-CoV-2 Wiki | 0.06 |
drug1211 | Usual Care Wiki | 0.06 |
drug1406 | stem cells Wiki | 0.06 |
drug980 | Ruxolitinib plus simvastatin Wiki | 0.06 |
drug922 | Quercetin Treatment Wiki | 0.06 |
drug1224 | Veru-111 Wiki | 0.06 |
drug470 | HCQ & AZ vs HCQ+SIR Wiki | 0.06 |
drug1284 | chloroquine Wiki | 0.06 |
drug334 | Cytokine Adsorption Wiki | 0.06 |
drug514 | Hydroxychloroquine - Daily Dosing Wiki | 0.06 |
drug520 | Hydroxychloroquine Pre-Exposure Prophylaxis Wiki | 0.06 |
drug997 | SARSCoV2 Convalescent Plasma Wiki | 0.06 |
drug78 | Apple Watch Series 5 Wiki | 0.06 |
drug774 | Normal Saline Infusion + Maximal intensive care Wiki | 0.06 |
drug1153 | There is no intervention in this study Wiki | 0.06 |
drug388 | EDP1815 Wiki | 0.06 |
drug624 | Lactated ringer's solution or sterile saline Wiki | 0.06 |
drug479 | Health Care Worker Survey Wiki | 0.06 |
drug29 | ASC09/ritonavir group Wiki | 0.06 |
drug998 | SF12, EQ-5D-5L and work status standardized quantitative assessments Wiki | 0.06 |
drug870 | Placebo: Emtricitabine/tenofovir disoproxil Placebo Wiki | 0.06 |
drug502 | Hydoxychloroquine or Chloroquine Wiki | 0.06 |
drug946 | Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2) Wiki | 0.06 |
drug803 | Others(No intervention) Wiki | 0.06 |
drug386 | ECG Wiki | 0.06 |
drug530 | Hydroxychloroquine Sulfate 600 mg once a day Wiki | 0.06 |
drug1087 | Standards of Care Wiki | 0.06 |
drug92 | Assessment of ventilator-associated pneumonia criteria Wiki | 0.06 |
drug1181 | Treatment and prophylaxis Wiki | 0.06 |
drug1166 | To assess for development of IgG antibodies against SARS-CoV2 Wiki | 0.06 |
drug550 | Hyperbaric oxygen Wiki | 0.06 |
drug543 | Hydroxychloroquine sulfate &Azithromycin Wiki | 0.06 |
drug1029 | Serum test Wiki | 0.06 |
drug965 | Ribavirin Wiki | 0.06 |
drug297 | Comprehensive treatment Wiki | 0.06 |
drug1280 | blood sampling Wiki | 0.06 |
drug734 | NaCl 0.9% Wiki | 0.06 |
drug1233 | Vitamins Wiki | 0.06 |
drug104 | Awake Proning Wiki | 0.06 |
drug214 | COVID-19 Specific T Cell derived exosomes (CSTC-Exo) Wiki | 0.06 |
drug1177 | Transfusion of COVID-19 convalescent plasma Wiki | 0.06 |
drug44 | Airway pressure release ventilation Wiki | 0.06 |
drug1109 | Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors Wiki | 0.06 |
drug1243 | Weekly Assessment Wiki | 0.06 |
drug1127 | Teleconsultation either by phone or by computer consultation Wiki | 0.06 |
drug58 | Amiodarone Wiki | 0.06 |
drug1074 | Standard screening strategy Wiki | 0.06 |
drug47 | Alferon LDO Wiki | 0.06 |
drug471 | HCQ + Intravenous Famotidine Wiki | 0.06 |
drug951 | Recombinant S protein SARS vaccine Wiki | 0.06 |
drug680 | Matched Placebo Hydroxychloroquine Wiki | 0.06 |
drug331 | Covid-19 presto test Wiki | 0.06 |
drug909 | Psychiatric counseling Wiki | 0.06 |
drug312 | Convalescent Plasma 2 Units Wiki | 0.06 |
drug48 | Allogeneic NK transfer Wiki | 0.06 |
drug1147 | The standard Macintosh laryngoscope Wiki | 0.06 |
drug292 | Collection of samples Wiki | 0.06 |
drug753 | Nitazoxanide 500 MG Wiki | 0.06 |
drug329 | Covid-19 + patients Wiki | 0.06 |
drug841 | Phosphate buffered saline Placebo Wiki | 0.06 |
drug119 | BAT + Calcifediol Wiki | 0.06 |
drug123 | BCG-Denmark Wiki | 0.06 |
drug1095 | Study Arm Wiki | 0.06 |
drug206 | COVID positive via testing Wiki | 0.06 |
drug1027 | Serology for Covid-19 Wiki | 0.06 |
drug1315 | hydroxychloroquine + azithromycin Wiki | 0.06 |
drug469 | HCQ & AZ Wiki | 0.06 |
drug1174 | Tradipitant Wiki | 0.06 |
drug478 | Halo Placebo Wiki | 0.06 |
drug1205 | Umbilical cord Wharton's jelly-derived human Wiki | 0.06 |
drug1144 | Thalidomide Wiki | 0.06 |
drug1400 | standard operating procedures Wiki | 0.06 |
drug1145 | The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care: Wiki | 0.06 |
drug708 | Monitoring Visit - Week 8 Wiki | 0.06 |
drug137 | Bacille Calmette-Guérin (BCG) Wiki | 0.06 |
drug124 | BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki | 0.06 |
drug827 | Patient sampling Wiki | 0.06 |
drug963 | Retrospective data collection Wiki | 0.06 |
drug1069 | Standard of care management Wiki | 0.06 |
drug1361 | observation Wiki | 0.06 |
drug234 | CT-imaging Wiki | 0.06 |
drug43 | Aerosolized Isotretinoin plus Tamoxifen Wiki | 0.06 |
drug1092 | Stool collection or fecal swab Wiki | 0.06 |
drug1301 | draw blood Wiki | 0.06 |
drug1320 | hyperbaric oxygen therapy (HBOT) Wiki | 0.06 |
drug585 | Insulin regimen Wiki | 0.06 |
drug746 | New screening strategy Wiki | 0.06 |
drug750 | Nigella Sativa / Black Cumin Wiki | 0.06 |
drug82 | Artemisinin / Artesunate Wiki | 0.06 |
drug541 | Hydroxychloroquine plus standard preventive measures Wiki | 0.06 |
drug540 | Hydroxychloroquine plus Nitazoxanide Wiki | 0.06 |
drug396 | Eicosapentaenoic acid gastro-resistant capsules Wiki | 0.06 |
drug1176 | Transcutaneous Auricular Vagus Nerve Stimulation Wiki | 0.06 |
drug381 | Drug: Isotretinoin plus Tamoxifen Wiki | 0.06 |
drug1410 | telehealth applications Wiki | 0.06 |
drug1206 | Umifenovir Wiki | 0.06 |
drug1207 | Unfractionated heparin Wiki | 0.06 |
drug884 | Point-of-Care Ultrasonography (POCUS) Wiki | 0.06 |
drug1345 | molecular testing for virus RNA using RT-PCR Wiki | 0.06 |
drug1099 | Study of immune-mediated mechanisms in patients tested positive for SARS-CoV-2 Wiki | 0.06 |
drug207 | COVID-19 Wiki | 0.06 |
drug581 | Inhaled nitric oxide gas Wiki | 0.06 |
drug74 | Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients Wiki | 0.06 |
drug466 | HB-adMSC Wiki | 0.06 |
drug1328 | laboratory biomarkers Wiki | 0.06 |
drug1241 | Web application users Wiki | 0.06 |
drug633 | Linagliptin Wiki | 0.06 |
drug397 | Ejaculated semen sample Wiki | 0.06 |
drug455 | Gargle/Mouthwash Wiki | 0.06 |
drug961 | ResCure™ Wiki | 0.06 |
drug539 | Hydroxychloroquine in combination of Azithromycin Wiki | 0.06 |
drug121 | BCG GROUP Wiki | 0.06 |
drug987 | SARS-CoV-2 PCR Wiki | 0.06 |
drug571 | Impact Event Score Wiki | 0.06 |
drug983 | SARILUMAB Wiki | 0.06 |
drug413 | Equipment with smartwatch throughout hospital stay on the general ward Wiki | 0.06 |
drug968 | Risk factors Wiki | 0.06 |
drug260 | Chinese Herbal Medicine Wiki | 0.06 |
drug2 | (Standard of Care) SoC Wiki | 0.06 |
drug1415 | thymosin alpha 1 Wiki | 0.06 |
drug463 | Group A HCQ Wiki | 0.06 |
drug1157 | Thoracic CT Scan Wiki | 0.06 |
drug808 | Oxygen-ozone therapy, probiotic supplementation and Standard of care Wiki | 0.06 |
drug402 | Elisa-test for IgM and IgG to SARS-CoV-2 Wiki | 0.06 |
drug559 | IV Deployment Of cSVF In Sterile Normal Saline IV Solution Wiki | 0.06 |
drug1268 | anti-SARS-CoV-2 convalescent plasma Wiki | 0.06 |
drug1330 | lopinavir/ritonavir Wiki | 0.06 |
drug591 | Interferon-β 1a Wiki | 0.06 |
drug866 | Placebo plus standard preventive measures Wiki | 0.06 |
drug102 | Aviptadil by intravenous infusion + maximal intensive care Wiki | 0.06 |
drug883 | Plitidepsin 2.5 mg/day Wiki | 0.06 |
drug1416 | trimethoprim/sulfamethoxazole Wiki | 0.06 |
drug1093 | Streptokinase Wiki | 0.06 |
drug434 | Favipiravir and Hydroxychloroquine Wiki | 0.06 |
drug327 | Corticosteroid Wiki | 0.06 |
drug1058 | Standard Public Health measures Wiki | 0.06 |
drug203 | COPAN swabbing and blood sample collection Wiki | 0.06 |
drug465 | Guided online support program Wiki | 0.06 |
drug564 | IgM and IgG diagnostic kits to SARS-CoV-2 Wiki | 0.06 |
drug64 | Angiotensin 1-7 Wiki | 0.06 |
drug177 | Blood sample for whole genome sequencing Wiki | 0.06 |
drug737 | Naltrexone Wiki | 0.06 |
drug461 | Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed Wiki | 0.06 |
drug642 | Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki | 0.06 |
drug1274 | bidirectional oxygenation mouthpiece Wiki | 0.06 |
drug990 | SARS-CoV-2 questionnaire survey Wiki | 0.06 |
drug986 | SARS-CoV-2 IgG Antibody Testing Kit Wiki | 0.06 |
drug481 | Helmet Continuous Positive Airway Pressure (CPAP) Wiki | 0.06 |
drug643 | Lopinavir and Ritonavir Tablets Wiki | 0.06 |
drug519 | Hydroxychloroquine Oral Product Wiki | 0.06 |
drug254 | Centricyte 1000 Wiki | 0.06 |
drug1038 | Sirolimus 1 MG/ML Wiki | 0.06 |
drug1261 | a specifically designed self-administered questionnaire Wiki | 0.06 |
drug632 | Liberase Enzyme (Roche) Wiki | 0.06 |
drug777 | Nutrition support Wiki | 0.06 |
drug829 | Patients admitted to Intensive Care Unit with SARS-CoV2 Wiki | 0.06 |
drug1098 | Study Group Wiki | 0.06 |
drug1201 | Ulinastatin Wiki | 0.06 |
drug1312 | hospitalized children with Covid19 Wiki | 0.06 |
drug52 | Alteplase 100 MG [Activase] Wiki | 0.06 |
drug1281 | captopril 25mg Wiki | 0.06 |
drug529 | Hydroxychloroquine Sulfate 400 mg twice a day Wiki | 0.06 |
drug1316 | hydroxychloroquine in combination with camostat mesylate Wiki | 0.06 |
drug498 | Human biological samples Wiki | 0.06 |
drug1369 | patients receiving nasal high flow Wiki | 0.06 |
drug649 | Lopinavir/ritonavir treatment Wiki | 0.06 |
drug324 | Cordio App Wiki | 0.06 |
drug871 | Placebo: Hydroxychloroquine Wiki | 0.06 |
drug1276 | blood donation SMS Wiki | 0.06 |
drug523 | Hydroxychloroquine Sulfate (HCQ) Wiki | 0.06 |
drug518 | Hydroxychloroquine Only Product in Oral Dose Form Wiki | 0.06 |
drug639 | Lopinavir / Ritonavir plus Ribavirin Wiki | 0.06 |
drug1309 | high flow nasal cannula (HFNC) Wiki | 0.06 |
drug771 | Non-convalescent Plasma (control plasma) Wiki | 0.06 |
drug55 | Aluminum hydroxide adjuvant (Alhydrogel®) Wiki | 0.06 |
drug1318 | hydroxychloroquine sulfate 200 MG Wiki | 0.06 |
drug1257 | Zinc Gluconate Wiki | 0.06 |
drug651 | Low Dose Radiation Therapy Wiki | 0.06 |
drug858 | Placebo Vaccine Wiki | 0.06 |
drug235 | CYNK-001 Wiki | 0.06 |
drug1337 | mRNA-1273 Wiki | 0.06 |
drug706 | Monitoring Visit - Baseline Wiki | 0.06 |
drug1165 | Tirofiban Injection Wiki | 0.06 |
drug1385 | recombinant human interferon Alpha-1b Wiki | 0.06 |
drug233 | CT-V Wiki | 0.06 |
drug847 | Piclidenoson Wiki | 0.06 |
drug422 | Experimental drug Wiki | 0.06 |
drug634 | Linagliptin 5 MG Wiki | 0.06 |
drug614 | Ivermectin plus Nitazoxanide Wiki | 0.06 |
drug890 | Povidone-Iodine 2% Wiki | 0.06 |
drug330 | Covid-19 Antibody testing (IgG and IgM) Wiki | 0.06 |
drug1313 | human cord tissue mesenchymal stromal cells Wiki | 0.06 |
drug263 | Chloroquine Diphosphate Wiki | 0.06 |
drug367 | Diagnosis of SARS-Cov2 by RT-PCR and : IgG, Ig M derologies in the amniotoc fluid, the blood cord and the placenta Wiki | 0.06 |
drug71 | Anti-SARS-CoV-2 Human Convalescent Plasma Wiki | 0.06 |
drug873 | Plaquenil 200Mg Tablet Wiki | 0.06 |
drug574 | Individualised Ayurveda Wiki | 0.06 |
drug995 | SARS-Cov-2 infection Wiki | 0.06 |
drug223 | COVID-19 positive via testing Wiki | 0.06 |
drug464 | Group B Control Wiki | 0.06 |
drug921 | Quercetin Prophylaxis Wiki | 0.06 |
drug936 | RPH-104 80 mg Wiki | 0.06 |
drug482 | Helmet non-invasive ventilation (NIV) Wiki | 0.06 |
drug609 | Isotonic saline 0.9% Wiki | 0.06 |
drug1371 | phone call Wiki | 0.06 |
drug391 | EUROIMMUN assay Wiki | 0.06 |
drug804 | Otilimab Wiki | 0.06 |
drug97 | Auricular neuromodulation Wiki | 0.06 |
drug618 | Ketamine Wiki | 0.06 |
drug1387 | research specific blood sample Wiki | 0.06 |
drug800 | Organicell Flow Wiki | 0.06 |
drug140 | Baricitinib Wiki | 0.06 |
drug266 | Chloroquine diphosphate Wiki | 0.06 |
drug1377 | prayer Wiki | 0.06 |
drug1282 | care modalities Wiki | 0.06 |
drug1238 | WJ-MSCs Wiki | 0.06 |
drug1225 | Video based aerobic exercise Wiki | 0.06 |
drug1384 | rapid salivary test Wiki | 0.06 |
drug271 | Ciclesonide Inhalation Aerosol Wiki | 0.06 |
drug67 | Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) Wiki | 0.06 |
drug1412 | this study is non- interventional Wiki | 0.06 |
drug462 | Group 2: control group with enoxaparin 40mg/d Wiki | 0.06 |
drug1399 | standard of care Wiki | 0.06 |
drug371 | Dipyridamole 100 Milligram(mg) Wiki | 0.06 |
drug437 | File scanning Wiki | 0.06 |
drug906 | Prone positioning (PP) Wiki | 0.06 |
drug580 | Inhaled budesonide Wiki | 0.06 |
drug515 | Hydroxychloroquine - Daily dosing Wiki | 0.06 |
drug790 | Olokizumab 64 mg Wiki | 0.06 |
drug521 | Hydroxychloroquine SAR321068 Wiki | 0.06 |
drug756 | Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki | 0.06 |
drug656 | Low or upper respiratory tract sample Wiki | 0.06 |
drug599 | Internet-delivered cognitive behavior therapy (ICBT) for dysfunctional worry related to the Covid-19 pandemic Wiki | 0.06 |
drug146 | Best Available Therapy Wiki | 0.06 |
drug1372 | pirfenidone Wiki | 0.06 |
drug531 | Hydroxychloroquine Sulfate 600 mg twice a day Wiki | 0.06 |
drug53 | Alteplase 50 MG [Activase] Wiki | 0.06 |
drug640 | Lopinavir / ritonavir tablets combined with Xiyanping injection Wiki | 0.06 |
drug192 | C-reactive protein Wiki | 0.06 |
drug799 | Oral placebo Wiki | 0.06 |
drug882 | Plitidepsin 2.0 mg/day Wiki | 0.06 |
drug1307 | gammaCore® Sapphire (non-invasive vagus nerve stimulator) Wiki | 0.06 |
drug855 | Placebo Comparator Wiki | 0.06 |
drug809 | Oxytocin Wiki | 0.06 |
drug494 | Honey Wiki | 0.06 |
drug361 | Detection of anti-COVID-19 antibody level Wiki | 0.06 |
drug524 | Hydroxychloroquine Sulfate + Azithromycin Wiki | 0.06 |
drug724 | NHANES smell and taste tests Wiki | 0.06 |
drug893 | Practice details Wiki | 0.06 |
drug1376 | plasma therapy using convalescent plasma with antibody against SARS-CoV-2 Wiki | 0.06 |
drug867 | Placebo solution Wiki | 0.06 |
drug1070 | Standard of care therapies Wiki | 0.06 |
drug1089 | Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki | 0.06 |
drug679 | Matched Placebo Wiki | 0.06 |
drug404 | Emtricitabine/tenofovir disoproxil Wiki | 0.06 |
drug170 | Blood collection on admission and longitudinally Wiki | 0.06 |
drug525 | Hydroxychloroquine Sulfate + Azythromycin Wiki | 0.06 |
drug1007 | Saline with Baby Shampoo Nasal Irrigation Wiki | 0.06 |
drug664 | MRx-4DP0004 Wiki | 0.06 |
drug619 | Ketogenic diet Wiki | 0.06 |
drug881 | Plitidepsin 1.5 mg/day Wiki | 0.06 |
drug1293 | convalescent plasma from recovered COVID 19 donor Wiki | 0.06 |
drug1146 | The Vie Scope laryngoscope Wiki | 0.06 |
drug171 | Blood collection on their first consultation and 10 to 14 days later Wiki | 0.06 |
drug1179 | Transfusion of standard Plasma. Wiki | 0.06 |
drug707 | Monitoring Visit - Week 4 Wiki | 0.06 |
drug491 | High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma Wiki | 0.06 |
drug1389 | risk factors Wiki | 0.06 |
drug758 | Nitric Oxide delivered via LungFit system Wiki | 0.06 |
drug892 | Powered Air purifying respirator Wiki | 0.06 |
drug77 | Apo-Hydroxychloroquine Wiki | 0.06 |
drug198 | CELLECTRA® 2000 Wiki | 0.06 |
drug430 | Famotidine Wiki | 0.06 |
drug814 | PLACEBO GROUP Wiki | 0.06 |
drug928 | Questionnaires for specific phobia Wiki | 0.06 |
drug38 | Acetylsalicylic acid Wiki | 0.06 |
drug782 | Observational (registry) Wiki | 0.06 |
drug282 | Clopidogrel Wiki | 0.06 |
drug584 | Injective placebo Wiki | 0.06 |
drug1025 | Serological test Wiki | 0.06 |
drug1014 | Sarilumab SAR153191 Wiki | 0.06 |
drug666 | MSC Treatment Wiki | 0.06 |
drug732 | NP-120 (Ifenprodil) Wiki | 0.06 |
drug538 | Hydroxychloroquine as post exposure prophylaxis Wiki | 0.06 |
drug191 | Burnout Wiki | 0.06 |
drug920 | Quality of Life Wiki | 0.06 |
drug1331 | lopinavir/ritonavir group Wiki | 0.06 |
drug1349 | muscle ultrasound Wiki | 0.06 |
drug160 | Biological/Vaccine: Angiotensin peptide (1-7) derived plasma Wiki | 0.06 |
drug420 | Examine the impact of COVID-19 during pregnancy Wiki | 0.06 |
drug416 | Escin Wiki | 0.06 |
drug1373 | placebo Wiki | 0.06 |
drug1067 | Standard of care Wiki | 0.05 |
drug1060 | Standard care Wiki | 0.05 |
drug318 | Convalescent plasma Wiki | 0.05 |
drug612 | Ivermectin Wiki | 0.05 |
drug1012 | Sarilumab Wiki | 0.05 |
drug739 | Nasal swab Wiki | 0.04 |
drug115 | Azithromycin Tablets Wiki | 0.04 |
drug1403 | standard therapy Wiki | 0.04 |
drug379 | Doxycycline Wiki | 0.04 |
drug839 | Peripheral blood draw Wiki | 0.04 |
drug565 | Imatinib Wiki | 0.04 |
drug450 | GLS-5300 Wiki | 0.04 |
drug173 | Blood draw Wiki | 0.04 |
drug532 | Hydroxychloroquine Sulfate Loading Dose Wiki | 0.04 |
drug1135 | Telmisartan Wiki | 0.04 |
drug864 | Placebo oral capsule Wiki | 0.04 |
drug213 | COVID-19 Serology Wiki | 0.04 |
drug741 | Nasopharyngeal swab Wiki | 0.04 |
drug888 | Povidone-Iodine Wiki | 0.04 |
drug79 | Arbidol Wiki | 0.04 |
drug533 | Hydroxychloroquine Sulfate Regular dose Wiki | 0.04 |
drug621 | L-ascorbic acid Wiki | 0.04 |
drug1040 | SivoMixx (200 billion) Wiki | 0.04 |
drug698 | Methylprednisolone Sodium Succinate Wiki | 0.04 |
drug401 | Electronic questionnaire Wiki | 0.04 |
drug151 | Bevacizumab Injection Wiki | 0.04 |
drug833 | Peginterferon Lambda-1A Wiki | 0.04 |
drug900 | Probiotic Wiki | 0.04 |
drug1100 | Sulfonatoporphyrin(TPPS) Wiki | 0.04 |
drug903 | Prone position Wiki | 0.04 |
drug891 | Povidone-Iodine Nasal Spray and Gargle Wiki | 0.04 |
drug264 | Chloroquine Sulfate Wiki | 0.04 |
drug37 | Acalabrutinib Wiki | 0.04 |
drug508 | Hydroxychloroquine + Azithromycin Wiki | 0.04 |
drug1052 | Standard Care Wiki | 0.04 |
drug731 | NORS (Nitric Oxide Releasing Solution) Wiki | 0.04 |
drug1391 | self-administered questionnaire Wiki | 0.04 |
drug310 | Convalescent Plasma (anti-SARS-CoV-2 plasma) Wiki | 0.04 |
drug363 | Dexamethasone Wiki | 0.04 |
drug1033 | Siltuximab Wiki | 0.04 |
drug309 | Convalescent Plasma Wiki | 0.04 |
drug1314 | hydroxychloroquine Wiki | 0.03 |
drug988 | SARS-CoV-2 convalescent plasma Wiki | 0.03 |
drug175 | Blood sample Wiki | 0.03 |
drug217 | COVID-19 convalescent plasma Wiki | 0.03 |
drug506 | Hydroxychloroquine (HCQ) Wiki | 0.03 |
drug1291 | convalescent plasma Wiki | 0.03 |
drug752 | Nitazoxanide Wiki | 0.03 |
drug587 | Interferon Beta-1B Wiki | 0.03 |
drug303 | Control Wiki | 0.03 |
drug1133 | Telerehabilitation Wiki | 0.03 |
drug1003 | Saline Wiki | 0.03 |
drug1041 | SnPP Protoporphyrin Wiki | 0.02 |
drug697 | Methylprednisolone Wiki | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
D018352 | Coronavirus Infections NIH | 0.80 |
D003141 | Communicable Diseases NIH | 0.35 |
D007239 | Infection NIH | 0.34 |
D013577 | Syndrome NIH | 0.21 |
D011014 | Pneumonia NIH | 0.19 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.18 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.18 |
D011024 | Pneumonia, Viral NIH | 0.16 |
D055371 | Acute Lung Injury NIH | 0.16 |
D003333 | Coronaviridae Infections NIH | 0.10 |
D014777 | Virus Diseases NIH | 0.10 |
D008171 | Lung Diseases, NIH | 0.10 |
D012327 | RNA Virus Infections NIH | 0.09 |
D058070 | Asymptomatic Diseases NIH | 0.08 |
D004408 | Dysgeusia NIH | 0.08 |
D016638 | Critical Illness NIH | 0.08 |
D012140 | Respiratory Tract Diseases NIH | 0.08 |
D016769 | Embolism and Thrombosis NIH | 0.07 |
D003924 | Diabetes Mellitus, Type 2 NIH | 0.07 |
D012141 | Respiratory Tract Infections NIH | 0.07 |
D000857 | Olfaction Disorders NIH | 0.07 |
D030341 | Nidovirales Infections NIH | 0.06 |
D011665 | Pulmonary Valve Insufficiency NIH | 0.06 |
D011649 | Pulmonary Alveolar Proteinosis NIH | 0.06 |
D001997 | Bronchopulmonary Dysplasia NIH | 0.06 |
D008595 | Menorrhagia NIH | 0.06 |
D006470 | Hemorrhage NIH | 0.06 |
D008659 | Metabolic Diseases NIH | 0.06 |
D018410 | Pneumonia, Bacterial NIH | 0.06 |
D006929 | Hyperaldosteronism NIH | 0.06 |
D003428 | Cross Infection NIH | 0.06 |
D014552 | Urinary Tract Infections NIH | 0.06 |
D000370 | Ageusia NIH | 0.06 |
D004700 | Endocrine System Diseases NIH | 0.06 |
D054990 | Idiopathic Pulmonary Fibrosis NIH | 0.06 |
D000309 | Adrenal Insufficiency NIH | 0.06 |
D012772 | Shock, Septic NIH | 0.06 |
D054559 | Hyperphosphatemia NIH | 0.06 |
D007008 | Hypokalemia NIH | 0.06 |
D012818 | Signs and Symptoms, Respiratory NIH | 0.06 |
D019446 | Endotoxemia NIH | 0.06 |
D019851 | Thrombophilia NIH | 0.06 |
D013313 | Stress Disorders, Post-Traumatic NIH | 0.06 |
D011565 | Psoriasis NIH | 0.06 |
D055501 | Macrophage Activation Syndrome NIH | 0.06 |
D009220 | Myositis NIH | 0.06 |
D044882 | Glucose Metabolism Disorders NIH | 0.06 |
D004617 | Embolism NIH | 0.05 |
D008173 | Lung Diseases, Obstructive NIH | 0.05 |
D012120 | Respiration Disorders NIH | 0.05 |
D003139 | Common Cold NIH | 0.04 |
D007154 | Immune System Diseases NIH | 0.04 |
D018805 | Sepsis NIH | 0.04 |
D053717 | Pneumonia, Ventilator-Associated NIH | 0.04 |
D009205 | Myocarditis NIH | 0.04 |
D013927 | Thrombosis NIH | 0.04 |
D000860 | Hypoxia NIH | 0.04 |
D011655 | Pulmonary Embolism NIH | 0.03 |
D011658 | Pulmonary Fibrosis NIH | 0.03 |
D007153 | Immunologic Deficiency Syndromes NIH | 0.03 |
D006333 | Heart Failure NIH | 0.03 |
D029424 | Pulmonary Disease, Chronic Obstructive NIH | 0.03 |
D009102 | Multiple Organ Failure NIH | 0.03 |
D054556 | Venous Thromboembolism NIH | 0.03 |
D040921 | Stress Disorders, Traumatic NIH | 0.03 |
D003920 | Diabetes Mellitus, NIH | 0.03 |
D053120 | Respiratory Aspiration NIH | 0.03 |
D012769 | Shock, NIH | 0.03 |
D013923 | Thromboembolism NIH | 0.03 |
D020246 | Venous Thrombosis NIH | 0.03 |
D017563 | Lung Diseases, Interstitial NIH | 0.03 |
D004417 | Dyspnea NIH | 0.03 |
D058186 | Acute Kidney Injury NIH | 0.02 |
D007251 | Influenza, Human NIH | 0.02 |
D006973 | Hypertension NIH | 0.02 |
D004630 | Emergencies NIH | 0.02 |
D018450 | Disease Progression NIH | 0.02 |
D007249 | Inflammation NIH | 0.02 |
D055370 | Lung Injury NIH | 0.01 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0002090 | Pneumonia HPO | 0.19 |
HP:0002088 | Abnormal lung morphology HPO | 0.10 |
HP:0005978 | Type II diabetes mellitus HPO | 0.07 |
HP:0011947 | Respiratory tract infection HPO | 0.07 |
HP:0000458 | Anosmia HPO | 0.07 |
HP:0000132 | Menorrhagia HPO | 0.06 |
HP:0002905 | Hyperphosphatemia HPO | 0.06 |
HP:0003765 | Psoriasiform dermatitis HPO | 0.06 |
HP:0002900 | Hypokalemia HPO | 0.06 |
HP:0000818 | Abnormality of the endocrine system HPO | 0.06 |
HP:0100614 | Myositis HPO | 0.06 |
HP:0000846 | Adrenal insufficiency HPO | 0.06 |
HP:0006517 | Alveolar proteinosis HPO | 0.06 |
HP:0000859 | Hyperaldosteronism HPO | 0.06 |
HP:0100724 | Hypercoagulability HPO | 0.06 |
HP:0010444 | Pulmonary insufficiency HPO | 0.06 |
HP:0000224 | Decreased taste sensation HPO | 0.06 |
HP:0006536 | Obstructive lung disease HPO | 0.05 |
HP:0012819 | Myocarditis HPO | 0.04 |
HP:0100806 | Sepsis HPO | 0.04 |
HP:0001907 | Thromboembolism HPO | 0.04 |
HP:0012418 | Hypoxemia HPO | 0.04 |
HP:0002206 | Pulmonary fibrosis HPO | 0.03 |
HP:0000819 | Diabetes mellitus HPO | 0.03 |
HP:0001635 | Congestive heart failure HPO | 0.03 |
HP:0002204 | Pulmonary embolism HPO | 0.03 |
HP:0002721 | Immunodeficiency HPO | 0.03 |
HP:0006510 | Chronic obstructive pulmonary disease HPO | 0.03 |
HP:0002625 | Deep venous thrombosis HPO | 0.03 |
HP:0006515 | Interstitial pneumonitis HPO | 0.03 |
HP:0002098 | Respiratory distress HPO | 0.03 |
HP:0001919 | Acute kidney injury HPO | 0.02 |
HP:0000822 | Hypertension HPO | 0.02 |
There are 279 clinical trials
Severe Acute Respiratory Syndrome (SARS) is a newly recognized illness that can be fatal. The purpose of this study is to better understand SARS by collecting samples of blood and other body fluids of people who have been exposed to SARS or who are suspected to have the illness. Up to 300 volunteers aged 18 years or older will be enrolled in this study. Participants will donate blood samples and, if appropriate, samples of fluid from the lungs, nose, or throat. Researchers will test these samples for proteins that control or mediate inflammatory or immune responses. The patterns of these proteins will reveal how SARS affects the body and the efforts the body makes to fight off the infection.
This study will evaluate and treat people with SARS, a new type of pneumonia (lung infection) originating in China. SARS is caused by a new virus that is easily transmitted from person to person. This study will look at the course of the disease; determine how the virus affects the body and how the body fights the infection; and evaluate diagnostic tests to quickly identify the disease. People 18 years of age and older with probable or suspected SARS may be eligible for this study. Close contacts of patients with SARS, patients who recovered from SARS, and NIH health care workers involved in the care of patients will also be enrolled. Patients with SARS who require hospitalization will be admitted to the NIH Clinical Center. Because SARS spreads easily, hospitalized patients will be in a room by themselves and will not be allowed any visitors. They will not leave their room except for tests, such as x-rays. All participants will have a full medical examination, including a medical history, physical examination, and blood tests. In addition, the participants undergo various tests and procedures as follows: - Probable and suspected SARS patients may be hospitalized or may be seen as outpatients. They are provided the treatment judged best for their disease, usually according to expressed or published recommendations. The best treatment for SARS is not yet known, and there have been no studies evaluating therapies. Outpatients are seen three times a week for 2 weeks, once a week for 4 more weeks, and then at 6 months. Patients have mouth and throat swabs taken three times a week for the first 2 weeks, then once a week for 4 more weeks. Blood is drawn three times a week for the first 2 weeks, then once at weeks 3, 4, and 6. If virus is still detectable after 6 weeks, nose washings and throat swabs are repeated until no virus is detected for 3 weeks in a row. In addition, patients provide urine and stool samples, have a chest x-ray and electrocardiogram, and undergo bronchoscopy and bronchial lavage. For the bronchoscopy, a bronchoscope (pencil-thin flexible tube) is passed into the large airways of the lung, allowing the physician to examine the airways. Cells and secretions from the airways are rinsed from the lung with salt water. A brush the size of a pencil tip is passed through the bronchoscope to scrape cells lining the airways and pieces of tissue are collected for analysis. - Close contacts of patients are evaluated twice a week for 2 weeks, then once a week for 2 more weeks. Blood is drawn at the first visit and then at 1, 2, and 4 weeks. Mouth and throat swabs, nose washings, and sputum collections are done twice a week for 2 weeks, then once a week for 2 more weeks. Urine and stool samples are collected once a week for 4 weeks. If virus from the nose or throat is still detectable after 4 weeks, weekly nose washings and throat swabs continue until no virus is detected for 3 weeks in a row. Blood may also be drawn during the weekly visits. - Recovered SARS patients provide blood, urine, and stool samples and have a mouth and throat swab and nose aspiration to see if the SARS virus is present. For the nasal aspiration, salt water is put in the nose and then suctioned out. Usually, these tests are done only once. If virus is detected, however, the nose washing, throat swabs and blood tests are repeated once a week until no virus is detected for 3 weeks in a row. - Health care workers document their contact with patients, use of isolation procedures and equipment, and any unexpected events that occur during contact. They are evaluated for symptoms of infection and provide a blood sample once a month
Highly communicable and virulent diseases, the ongoing threat of emerging infectious diseases, and the prospect of bio-terrorism have become part of the new reality for health care workers. SARS transmission has occurred despite the use of droplet, contact, and airborne precautions. Potential explanations for some of the episodes of “through-precautions” transmission include the possibility of contamination during removal of protective clothing. The recommended protective systems (PPS) for aerosol generating procedures set out by the US Center for Disease Control and Prevention (CDC) and the Ontario Ministry of Health and Long Term Care (MOHLTC) differ. The failure of a PPS may be associated with significant consequences in terms of the morbidity and mortality of front-line health care workers. The purpose of this study is to determine if a difference exists between the rate of self-contamination due to deficiencies in contact precautions for individuals wearing either the CDC or MOHLTC recommended PPS. Study participants will don one of the two recommended PPS, be “contaminated” with an indicator that becomes visible under ultraviolet light, and then assessed for contamination of clothing layers and skin after removal of the PPS. They will then repeat the procedure using the other PPS.
Severe acute respiratory syndrome (SARS) is a new threat to public health since November, 2002. The SARS is highly contagious and is believed to be transmitted by person-to-person through droplet and direct contact. The patients present with fever, chills, cough, myalgia, dyspnea, and diarrhea. The symptoms aggravate in the second week and nearly 40% of the patients develop respiratory failure that requires assisted ventilation. The mortality rate is reported as 6.5%-7%. After several months, the world scientists found the etiology to be a new coronavirus not belonging to the previous coronavirus group I, II and III. The new virus is called SARS associated coronavirus (SARS-CoV). Although the high morbidity and mortality of SARS occurred in adults, there was rare mortality reported in the children. The report from Hong Kong pointed out that the symptoms of SARS in younger children were milder and the clinical course was not as aggressive as in adults. Therefore, the aim of the project is to design the experiment to see the differences of immunological responses to SARS-CoV protein in healthy younger children, teenagers, and adults. The investigators hope that the result could explain the reason for milder disease in younger children and the immunological pathogenesis of SARS.
The purpose of this trial is to conduct a randomized dose-ranging study to evaluate the safety and activity of orally administered low dose interferon alfa-n3 as an antiviral and immunomodulator in asymptomatic subjects with recent exposure to a person with severe acute respiratory syndrome (SARS) or possible SARS. The primary objective of this pilot study is to determine an Alferon LDO dose level that increases or upregulates genes known to be mediators of interferon response. Secondary endpoints include the development of SARS symptomatology, rate of hospitalization, and mortality rate. In the event that no subjects with recent exposure to a person with SARS or possible SARS are available, this study will be conducted with 10 normal volunteers.
Description: Increased expression of genes known to be mediators of interferon response.
Measure: Gene expression analysis Time: Days 0, 2, 6, 11, 12, 15, 20 and 40Description: Development of clinical SARS-CoV symptomatology
Measure: SARS CoV Antibody Time: Days 0, 15, 20 and 40Description: Hospitalization for SARS-CoV infection and Death
Measure: SARS-CoV infectionThe purpose of this study is to collect plasma by apheresis from patients who have recovered from Severe Acute Respiratory Syndrome (SARS). This plasma will be processed into a SARS-antibody enriched intravenous immune globulin (IVIG) product. This product will then be available for use in a clinical trial if a SARS epidemic recurs. Potentially eligible participants are people between 18 and 56 years of age who have recovered from SARS. Potential participants will undergo three sequential screenings to determine their eligibility for this study. Eligible participants will then be scheduled for plasmapheresis. After apheresis, additional testing will be performed on a sample of the source plasma. Once the sample has been tested and cleared, the source plasma will be shipped to the United States to the storage facility and finally to the site of manufacturing of the IVIG product. Participants may donate plasma again after 14 days. The study will not have a direct benefit for participants. However, participation may help develop a treatment that could be useful to other people who become infected with SARS.
The study aims to examine whether the combination of Lopinavir/Ritonavir plus Ribavirin for treatment of severe acute respiratory syndrome (SARS) is superior to placebo.
Following the sudden and unexpected emergence of influenza A(H1N1)pdm09 (2009 H1N1) virus, this observational study was initiated to estimate rates of morbidity and mortality and to examine predictors of severity among participants with 2009 H1N1 infection. In 2011, as surveillance indicated that 2009 H1N1 virus was co-circulating with other seasonal influenza A and B viruses worldwide, the protocol was expanded to include other influenza A subtypes and influenza B viruses. The current version of the protocol (released in August 2013) further broadens the scope of this observational study. With the recognition that novel respiratory viruses other than novel influenza A viruses, e.g., Middle East Respiratory Syndrome Coronavirus (MERS-CoV), could become prevalent and of major public health importance, the objectives of this protocol have been expanded.
The investigators aim to do serosurvey of healthcare-personnel who had participated in treatment of confirmed patients of Middle-East respiratory syndrome. The investigators collected the base-line (pre-exposure) serum of healthcare-personnel in a few centers, and will collect the post-exposure serum from about 25-30 centers in which confirmed MERS patients had been treated. The investigators will deduct the seroprevalence of MERS-CoV IgG among the healthy healthcare-personnel, and calculate the sero-conversion rate if possible. The investigators will subdivided the seroprevalence according to the degree of exposure and preparedness of personal protective equipment.
Description: MERS-CoV IgG(+)
Measure: IgG(+) Time: up to 4-5 monthThis is a quality improvement study with the purpose of observing and measuring the effects of implementation of a proven standardized lung protective ventilation protocol in the new electronic medical record system iCentra across all Intermountain Healthcare hospitals. Approximately 14,000 records will be accessed for this study from a database of mechanically ventilated patients established for quality improvement purposes. The investigators hypothesize that implementation of a standardized computerized lung protective ventilation protocol across all Intermountain Healthcare hospitals will be feasible, will decrease initial tidal volumes to the target 6 ml/kg PBW, and will improve outcomes. The objectives of this study are to: - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in patients with acute respiratory failure requiring mechanical ventilation - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in the sub-group of patients with the acute respiratory distress syndrome (ARDS) - Measure compliance with the implementation of a computerized lung protective ventilation protocol at 12 Intermountain Healthcare hospitals
This is a Phase 1, first-in-human (FIH), single site, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of single ascending doses of a co-administered (1:1, w/w) combination of REGN3048 and REGN3051 mAb's, administered IV in healthy adult volunteers. Study duration of approximately 16 months. Approximately 48 evaluable subjects will be enrolled in the study, eight (8) subjects in each one of 6 sequential ascending IV dose cohorts. In each cohort, subjects will be randomized to receive mAb's REGN3048 and REGN3051 (6 subjects) or placebo (2 subjects). Primary Objective: To assess the safety and tolerability of REGN3048 and REGN3051 following co-administration of single, ascending IV doses of 1.5, 5, 15, 25, 50, and 75 mg/kg of each of the two mAb's.
Non tuberculous mycobacteria (NTM), Burkholdria spp, Aspergillus in the lung are almost impossible to eradicate with conventional antibiotics. In addition COVID-19 has know current treatment. These patients have few options to treat their lung infection. Nitric oxide has broad bactericidal and virucidal properties. It has been shown that nitric oxide was safe to be inhaled for similar cystic fibrosis patients and reduced drug resistant bacteria in the lungs. Further, research indicates that clinical isolates of NTM, Burkholderia spp, Aspergillus spp and Corona-like viruses can be eradicated by 160ppm NO exposure in the laboratory petri dish. This is not the first time inhaled NO treatment has been used in patients with difficult lung infections. This study will provide more data to see if NO therapy can reduce the bacterial load in the lungs, help the patients breath better; and in the case of COVID-19 act as a anti-viral agent resulting in the reduction of incidence of oxygen therapy, mechanical assistance of BIPAP, CPAP, intubation and mechanical ventilation during the study period.
Description: Measure the number of unanticipated adverse events over the duration of the study protocol
Measure: Measure the safety of 160ppm inhaled nitric oxide delivery in NTM subjects Time: 26 DaysDescription: Measure the change in absolute FEV1.0 change from baseline during 160 ppm inhalation therapy
Measure: Measure the effect of 160ppm inhaled nitric oxide delivery on lung spirometry in NTM subjects Time: Day 5,12,19 and 26Description: Measure the difference from baseline NTM species bacterial load (0 to +4) in sputum during 160ppm nitric oxide inhalation therapy
Measure: Measure the antimicrobial effect of 160ppm inhaled nitric oxide on lung NTM bacterial load in the sputum Time: Day 19 and 26Description: Measure the difference from baseline CRISS (0-100) during 160ppm nitric oxide inhalation therapy (lower score represents higher quality of life)
Measure: Measure the effect of 160ppm inhaled nitric oxide on Quality of Life (CRISS) Score Time: Day 19 and 26Description: Measuring reduction in the incidence of mechanical assistance including oxygen therapy, BIPAP, CPAP, intubation and mechanical ventilation during the study period.
Measure: Sub-Study Primary Endpoint(s): Efficacy to reduce respiratory interventions Time: Day 26Description: Measured by death from all causes
Measure: Efficacy in reduction of mortality Time: Day 26Description: Assessed by time to negative conversion of COVID-19 RT-PCR from upper respiratory tract
Measure: Antiviral effect Time: Day 26Description: Time to clinical recovery as measured by resolution of clinical signs
Measure: Efficacy on clinical improvement Time: Day 26Description: Measured by change in the Modified Jackson Cold Score
Measure: Efficacy on the respiratory symptoms Time: Day 26SARS-CoV has caused severe epidemic respiratory disease in human populations. By July 2003, a total of 8,096 probable cases of SARS had been reported including 774 deaths in 27 countries, around one-third of which were health care workers (HCWs). Previous studies have been reported about long-term impacts of SARS infection, including lung function deficiency, steroid-induced osteonecrosis, reduced exercise capacity, and impairment in health-related quality of life (HRQoL). HCWs, especially nurses, have been reported to experience greater psychological distress, particularly increased levels of posttraumatic stress symptomatology (PTSS). But the very complex impacts of this fatal infection on HCWs have not been fully elucidated. It is thus important to follow these occupational patients to detect and manage multi-organ sequelae and functional impairment.
Description: Disabilities arising from physical injuries and/or mental stresses
Measure: All-cause disability Time: Evaluations would be finished within 90 days after enrollment.Description: The interrelationship between the workings of the heart and lung organs would be assessed by assessed by 6MWT (6-min walk test)
Measure: Cardiopulmonary function Time: Evaluations would be finished within 90 days after enrollment.Description: Quality of life would be assessed by the Medical Outcomes Study 36-item short form version 2 (SF-36)
Measure: Life Life quaities mental distress Time: Evaluations would be finished within 90 days after enrollment.Background: Intra-alveolar clotting and alveolar collapse in ARDS is due to alveolar capillaries epithelial and leakage. Subsequently, collapse induces hypoxemia that is resistant to recruitment (RM). Heparin and Streptokinase may prevent or dissolve intra-alveolar fibrin clot respectively helping alveolar re-expansion. We examined and compared the effect of nebulizing Heparin versus Streptokinase on reversing this pathology. Methods: Sixty severe ARDS (PaO2/FiO2<100) patients and failure of RM, prone position (PP) and neuromuscular block (NMB) were partially randomised into Group (I): (n=20) received nebulized Heparin 10000 IU/4h. Group (II): (n=20) received nebulized Streptokinase 250,000 IU/4h. Group (III): (n=20) received conservative management. Randomization to either Heparin or Streptokinase groups was applied to patients whom guardian accepted participation, while those who declined participation were followed-up as a control. The primary outcome was the change in PaO2/FiO2; the secondary outcomes included the change in compliance, plateau pressure, ventilation-off days, coagulation and ICU mortality.
Description: Change in the ratio of arterial oxygen tension to fraction of inspired oxygen from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.
Measure: Change in PaO2/FiO2 ratio Time: daily over eight daysDescription: Change in the plateau airway pressure during ventilation from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.
Measure: Change in the plateau pressure Time: daily over eight daysDescription: change in volume of the lungs per change in pressure during ventilation from the baseline (day 0, before randomization and or the start of intervention) to day 1 to day 8 after the randomization and or start of intervention.
Measure: Change in the pulmonary compliance Time: daily over eight daysDescription: Number of patients who are discharged alive
Measure: ICU survival rate Time: At the end of ICU stay up to one year after the start of recruitmentDescription: the total duration the patient stays in ICU
Measure: ICU length of stay Time: At the end of ICU stay up to one year after the start of recruitmentDescription: number of patients who required tracheostomy
Measure: Tracheostomy rate Time: During ICU stay up to one month after the start of recruitmentThe study explores the efficacy of lopinavir plus ritonavir and arbidol in treating with novel coronavirus infection. As a result this study would provide evidence for the clinical usage of these drugs in the future .
Description: Novel coronaviral nucleic acid is measured in nose / throat swab at each time point.
Measure: The rate of virus inhibition Time: Day 0, 2, 4, 7, 10, 14 and 21Description: Body temperature will be followed everyday during time frame.
Measure: The disease prorogation-temperature Time: Day 0 till day 21Description: Respiratory rate will be followed everyday during time frame.
Measure: The disease prorogation-respiratory function 1 Time: Day 0 till day 21Description: Oxygen saturation of blood will be followed everyday during time frame.
Measure: The disease prorogation-respiratory function 2 Time: Day 0 till day 21Description: Chest imaging will be taken at each time point.
Measure: The disease prorogation-respiratory function 3 Time: Day 0, 4, 7, 10, 14 and 21Description: Blood pressure and heart rate will be followed everyday during time frame.
Measure: Patients health condition-routine test Time: Day 0 till day 21Description: Liver function will be assessed as AST, ALT and TBIL at each time point.
Measure: Patients health condition-liver function Time: Day 0, 4, 7, 10, 14 and 21Description: Kidney function will be assessed as eGFR and creatine clearance rate at each time point.
Measure: Patients health condition-kidney function Time: Day 0, 4, 7, 10, 14 and 21Description: Blood routine and myocardial enzyme will be measured at each time point.
Measure: Patients health condition-other blood routine test Time: Day 0, 4, 7, 10, 14 and 21Description: Flow cytometry classification and counting and cytokines will be measured at each time point.
Measure: Patients health condition-blood routine test Time: Day 0, 4, 7, 10, 14 and 21Base on Arbidol antiviral therapy,the investigators conduct a randomized, open-label trial to evaluate and compare the safety and efficacy of ASC09 /ritonavir and lopinavir/ritonavir in patients with 2019-nCoV pneumonia.
Description: Defined as(one of them) SPO2≤ 93% without oxygen supplementation, PaO2/FiO2 ≤ 300mmHg or RR ≥ 30 breaths per.
Measure: The incidence of composite adverse outcome Time: 14 daysDescription: Clinical recovery was defined as( one of them): sustained (48 hours) alleviation of illness based on symptom scores (fever, cough,diarrhea, myalgia, dyspnea) all being absent and no evidence for progression (newly-presented dyspnea, SpO2 decline ≥3%, respiratory rate ≥ 24 breaths per min without supplemental oxygen). Or undectable viral RNA.
Measure: Time to recovery Time: 14 daysInfectious disease is the single biggest cause of death worldwide. New infectious agents, such as the SARS, MERS and other novel coronavirus, novel influenza viruses, viruses causing viral haemorrhagic fever (e.g. Ebola), and viruses that affect the central nervous system (CNS) such as TBEV & Nipah require investigation to understand pathogen biology and pathogenesis in the host. Even for known infections, resistance to antimicrobial therapies is widespread, and treatments to control potentially deleterious host responses are lacking. In order to develop a mechanistic understanding of disease processes, such that risk factors for severe illness can be identified and treatments can be developed, it is necessary to understand pathogen characteristics associated with virulence, the replication dynamics and in-host evolution of the pathogen, the dynamics of the host response, the pharmacology of antimicrobial or host-directed therapies, the transmission dynamics, and factors underlying individual susceptibility. The work proposed here may require sampling that will not immediately benefit the participants. It may also require analysis of the host genome, which may reveal other information about disease susceptibility or other aspects of health status.
Description: Describe the clinical features of the illness or syndrome (cardio-respiratory signs or symptoms, and laboratory results) and complications, and determinants of severity. Assessment daily for 15 days, then weekly until max 100 days, then 3 and 6 months.
Measure: Clinical features Time: 6 monthsDescription: Describe the response to treatments (including supportive care and novel therapeutics) by clinical, biological, radiological and virological assessments. Assessment daily for 15 days, then weekly until max 100 days, then 3 and 6 months.
Measure: Response to treatment Time: 6 monthsDescription: high-throughput sequencing of pathogen genomes obtained from respiratory tract, blood, urine, stool, CSF and other samples. Assessment on Day 1, Day 2, Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15 then weekly until max 100 days, then 3 and 6 months.
Measure: Pathogen replication, excretion and evolution, within the host Time: 6 monthsDescription: Characterise the innate and acquired immune responses, circulating levels of immune signalling molecules and gene expression profiling in peripheral blood. Assessment on Day 1, Day 2, Day 3, Day 5, Day 7, Day 9, Day 11, Day 13, Day 15 then weekly until max 100 days, then 3 and 6 months.
Measure: Immune host responses to infection and therapy Time: 6 monthsDescription: Identify host genetic variants associated with disease progression or severity
Measure: Host genetic variants Time: Day 1There was an interaction between mortality, nutritional intake and the Nutrition Risk in Critically ill (NUTRIC) score suggesting that those with higher NUTRIC scores benefited the most from increasing nutritional intake. Yet limited data were in Chinese patients. The current outbreak of novel coronavirus, named COVID-19, was first reported from Wuhan, China on Dec ember 31 , 2019. There are about 16% patients need ICU admission. The objective of this study is to validation of the "NUTRIC" nutritional risk assessment tool in Chinese ICU patients diagnosed as COVID-19.
The novel identified coronavirus (SARS-CoV-2) in 2019 causes an nationwide outbreak as well as public health crisis in China, and expands globally. Pulmonary edema is one of the most detrimental symptoms and usually presents in severe and critical coronavirus disease (COVID-19), resulting in dyspnea, acute lung injury (ALI) ,acute respiratory distress syndrome (ARDS), and even death. Recent evidence revealed higher levels of blood Vascular Endothelial Growth Factor (VEGF) in COVID-19 patients compared with healthy controls. VEGF is considered as the most potent vascular permeability inducers. Numerous studies have revealed that VEGF was a key factor and a potential therapeutic target in ALI and ARDS. Bevacizumab, an anti-VEGF drug, approved by the FDA on February 26, 2004 and widely used in clinical oncotherapy, is a promising drug for ALI/ARDS in COVID-19 through suppression of pulmonary edema.
Description: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio
Measure: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio Time: 24 hoursDescription: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio
Measure: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio Time: 72 hoursDescription: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio
Measure: Partial arterial oxygen pressure (PaO2) to fraction of inspiration O2 (FiO2) ratio Time: 7 daysDescription: Liker scale: The patient grades his current breathing compared to when he first started the drug (from -3 to 3). "0" = no change, "1" =minimally better, "2" =moderately better, "3" =markedly better, "-1" =minimally worse, "-2" =moderately worse, "-3" =markedly worse
Measure: Degree of dyspnea (Liker scale) Time: 72 hoursDescription: The patient grades the current breathing condition of himself compared to when he first started the drug (from -3 to 3).
Measure: Degree of dyspnea (Liker scale) Time: 7 daysDescription: Visual analog scale (VAS): The patient draws a horizontal line on an axial graph (from 0 to 100) to show the degree of how he feels about breathing. The number "0" equals the worst breathing the patient has ever felt and the number "100" equals the best he has ever felt.
Measure: Degree of dyspnea (VAS) Time: 72 hoursDescription: Visual analog scale (VAS): The patient draws a horizontal line on an axial graph (from 0 to 100) to show the degree of how he feels about breathing. The number "0" equals the worst breathing the patient has ever felt and the number "100" equals the best he has ever felt.
Measure: Degree of dyspnea (VAS) Time: 7 daysDescription: The degree of exudation on Chest CT
Measure: The area of lung lesions on Chest CT Time: 7 daysDescription: The degree of lung exudation on Chest CT
Measure: The degree of lung exudation on Chest CT Time: 7 daysDescription: transcutaneous oxygen saturation
Measure: SpO2 Time: 24 hoursDescription: transcutaneous oxygen saturation
Measure: SpO2 Time: 72 hoursDescription: transcutaneous oxygen saturation
Measure: SpO2 Time: 7 daysDescription: Partial arterial oxygen pressure
Measure: PaO2 Time: 24 hoursDescription: Partial arterial oxygen pressure
Measure: PaO2 Time: 72 hoursDescription: Partial arterial oxygen pressure
Measure: PaO2 Time: 7 daysDescription: CRP
Measure: CRP Time: 72 hoursDescription: CRP
Measure: CRP Time: 7 daysDescription: hs-CRP
Measure: hs-CRP Time: 72 hoursDescription: hs-CRP
Measure: hs-CRP Time: 7 daysDescription: All-cause mortality
Measure: All-cause mortality Time: 7 daysDescription: All-cause mortality
Measure: All-cause mortality Time: 14 daysA combination of lopinavir/ ritonavir, ribavirin and interferon beta-1b will expedite the recovery, suppress the viral load, shorten hospitalisation and reduce mortality in patients with 2019-n-CoV infection compared with to lopinavir/ ritonavir
Description: Time to negative NPS 2019-n-CoV RT-PCR
Measure: Time to negative NPS Time: Up to 1 monthDescription: Time to negative saliva 2019-n-CoV RT-PCR
Measure: Time to negative saliva Time: Up to 1 monthDescription: Time to NEWS of 0
Measure: Time to clinical improvement Time: Up to 1 monthDescription: Length of hospitalisation
Measure: Hospitalisation Time: Up to 1 monthDescription: 30-day mortality
Measure: Mortality Time: Up to 1 monthDescription: Cytokine/ chemokine changes
Measure: Immune reaction Time: up to 1 monthDescription: Adverse events during treatment
Measure: Adverse events Time: up to 1 monthDescription: Time to negative NPS, saliva, urine and stool 2019-n-CoV RT-PCR
Measure: Time to negative all clinical specimens Time: up to 1 monthThe study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.
Outbreak of 2019 Novel Coronavirus infection started in Wuhan and quickly spread to the world. Suspected patients were isolated and treated in our department. Clinical data was recorded to investigate the clinical features of patients confirmed and excluded diagnosed of 2019 Novel Coronavirus infection.
Description: If the patient will survive after comprehensive treatment
Measure: Survival rate Time: 28 daysDescription: Images of chest computed tomography are obtained to find out the changes in the course of treatment
Measure: Chest computed tomography Time: 28 daysDescription: Time for recovery from admission to discharged
Measure: Recovery Time Time: 28 daysDescription: A self-rating depression scale (SCL-90) will be finished from patients and medical staff. There are 90 questions. Each question scores from 1 to 5. Minimum score is 90, maximun score is 450. High scores indicate poor condition.
Measure: Depression evaluation Time: 28 daysSince Dec 2019, over 70000 novel coronavirus infection pneumonia (NCIP) patients were confirmed. 2019 novel coronavirus (2019 nCoV) is a RNA virus, which spread mainly from person-to-person contact. Most of the symptoms are non-specific, including fever, fatigue, dry cough. Sever NCIP patients may have shortness of breath and dyspnea, and progress to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). The mortality is reported to be around 2.3%. Thus, early detection and early treatment is very important to the improvement of NCIP patients' prognosis. At present, NCIP RNA detection of pharyngeal swab specimen by RT-PCR is recommended. However, due to the universal susceptibility to 2019 nCoV in general population and limited number of NCIP RNA detection kits available, to identify an efficient screening strategy is urgently needed. This study aim to develop and validate the diagnostic accuracy and screening efficiency of a new NCIP screening strategy, which can benefit the disease prevention and control.
Description: The screening accuracy of the two screening strategies were calculated and compared.
Measure: Screening accuracy Time: 1 monthDescription: The costs of the two screening strategies were recorded. Cost-effectiveness analysis were performed and compared.
Measure: Cost-effectiveness analysis Time: 1 monthThe acute lung injury caused by SARS and 2003 were both related to the inflammatory cytokine storm in patients. The biochemical test showed abnormal increase in related indicators such as interleukin-8, and CT images showed a medical "white" lung". According to the experience of SARS treatment in 2003, the use of hormones will indeed help the patients to alleviate their illness, but patients who survived SARS either had too much hormone at that time and took too long. Although the lungs could recover, but the femoral head was necrotic Either the amount of hormones was very conservative at the time, which kept the lungs in the storm of inflammatory factors, leading to the emergence of irreversible pulmonary fibrosis. So is there a medicine that can anti-inflammatory, reduce the load of hormone use, and have the effect of treating and preventing pulmonary fibrosis complicated by severe viral lung? At present, pirfenidone has achieved encouraging results in the treatment of idiopathic Pulmonary Fibrosis (CTD-ILD) diseases. It is particularly encouraging that the values announced at the 2019 ATS Annual Conference suggest that pirfenidone has more anti-inflammatory and anti-oxidant effects than its own outstanding anti-fibrotic ability. The data shows early use, Its strong anti-SOD activity can effectively inhibit IL-1beta and IL-4, and can open the prevention mode of pulmonary interstitial fibrosis. Based on the above, this project intends to make the following scientific assumptions: based on the homology of the pathogens of the new coronavirus-infected pneumonia and the coronavirus infection of pneumonia in 2003, the similarities in the occurrence and development of the disease, that is, the pulmonary inflammatory storm occurs first, and thereafter The progress of fibrosis and the progressive decline of lung function and mortality are higher than those of ordinary pneumonia. We hope that by adding pirfenidone as a treatment program in addition to standard treatment, it will be a new and severe type of coronavirus infection. Patient clinical treatment provides an effective and practical method.
Description: Lesion area of chest CT image at 4 weeks
Measure: chest CT Time: 4 weeksDescription: Absolute change in pulse oxygen from baseline
Measure: Finger pulse oxygen Time: 4 weeksDescription: Absolute change in blood gas from baseline
Measure: blood gas Time: 4 weeksDescription: Absolute change in total score of King's brief questionnaire for interstitial Absolute change in total score of King's brief questionnaire for interstitial pulmonary disease (k-bild) from baseline at week 4
Measure: K-BILD Time: 4 weeksDescription: Time to death within 4 weeks due to respiratory problems
Measure: death Time: 4 weeksDescription: Time to disease progression or death within 4 weeks
Measure: Time to disease progression or death within 4 weeks Time: 4 weeksDescription: lymphocyte count
Measure: blood Time: 4 weeksDescription: Absolute change in viral nucleic acid from baseline
Measure: viral nucleic acid Time: 4 weeksDescription: Pulmonary fibrosis survival symptoms absolute changes in dyspnea score from baseline
Measure: dyspnea score Time: 4 weeksDescription: changes in blood inflammatory indexes
Measure: blood Time: 4 weeksDescription: Absolute change in cough scores for pulmonary fibrosis survival symptoms from baseline
Measure: cough scores Time: 4 weeksThe scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (COVID-19) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on COVID-19 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.
Description: The primary outcome will be the proportion of patients with mild COVID2019 who deteriorate to a severe form of the disease requiring intubation and mechanical ventilation. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.
Measure: Reduction in the incidence of intubation and mechanical ventilation Time: 28 daysDescription: Mortality from all causes
Measure: Mortality Time: 28 daysDescription: Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or a nasopahryngeal swab
Measure: Negative conversion of COVID-19 RT-PCR from upper respiratory tract Time: 7 daysDescription: Time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air) and alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent).
Measure: Time to clinical recovery Time: 28 daysThe investigators will enroll 102 patients with a confirmed diagnosis of COVID-19. Patients will be randomized to receive either inhaled nitric oxide (per protocol) or placebo. ICU Standards of care will be the institution's own protocols (such as ventilation strategies and use and dose of antivirals and antimicrobials, steroids, inotropic and vasopressor agents).
Description: Percentage of patients that have a PaO2/FiO2 ratio steadily > 300 in ambient air
Measure: SARS-free patients at 14 days Time: 14 days since beginning of treatmentDescription: Composite outcome in which: Death=0, Days of treatment =1
Measure: SARS-free days at 28 days Time: 28 daysDescription: Composite outcome in which: Death=0, Days of treatment =1
Measure: SARS -free days at 90 days Time: 90 daysDescription: Incidence
Measure: Renal Replacement Therapy Time: 28 daysDescription: Incidence
Measure: Liver Failure Time: 28 daysDescription: Incidence of patients requiring VA-ECMO, LVAD, IABP
Measure: Mechanical Support of Circulation Time: 28 daysDescription: In ambient air if possible
Measure: PaO2/FiO2 ratio in ambient air Time: daily for 28 daysIn December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay. In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of lung injury caused by COVID-19 can be an alternative target for current treatment. Xiyanping injection has anti-inflammatory and immune regulation effects. This study is a Randomized, Parallel Controlled Clinical Study to treat patients with COVID-19 infection.
Description: The time from study drug use to complete fever reduction and cough recovery is measured in hours.
Measure: Clinical recovery time Time: Up to Day 28Currently, the growing epidemic of a new coronavirus infectious disease (Covid-19) is wreaking havoc worldwide, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a RNA virus that display high similarity in both genomic and proteomic profiling with SARS-CoV that first emerged in humans in 2003 in China. Therefore, preventing and controlling the pandemic occurrences are extremely urgent as a global top priority. Due to the lack of effective antiviral drugs, patients may be treated by only addressing their symptoms such as reducing fever. Clinical autopsies from SARS-CoV-infected patients demonstrated that there were major pathological changes in the lungs, immune organs, and small systemic blood vessels with vasculitis. However, the detection of SARS-CoV were primarily found in the lung and trachea/bronchus, but was undetectable in spleen, lymph nodes, bone marrow, heart and aorta, highlighting the overreaction of immune responses induced by viral infection were really harmful, resulting in the pathogenesis of lungs, immune organs, and small systemic blood vessels. To this respect, immune modulation strategy may be potentially beneficial to enhance anti-viral immunity and efficiently reduce the viral load, improve clinical outcomes, expedite the patient recovery, and decline the rate of mortality in patients after being infected with SARS-CoV-2. Tianhe Stem Cell Biotechnologies Inc. has developed a novel globally-patented Stem Cell Educator (SCE) technology designed to reverse the autoimmune response in Type 1 diabetes (T1D), Alopecia Areata (AA) and other autoimmune diseases. SCE therapy uses human multipotent cord blood stem cells (CB-SC) from human cord blood. Their properties distinguish CB-SC from other known stem cell types, including mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC). Several clinical studies show that SCE therapy functions via CB-SC induction of immune tolerance in autoimmune T cells and restore immune balance and homeostasis in patients with T1D, AA and other inflammation-associated diseases. To correct the overreaction of overreaction of immune responses, the investigators plan to treat SARS-CoV-2 patients with Stem Cell Educator therapy.
Description: The feasibility will be evaluated by the number of Covid-19 patients who were unable to complete SCE Therapy.
Measure: Determine the number of Covid-19 patients who were unable to complete SCE Therapy Time: 4 weeksDescription: Measurements of immune markers' changes will be preformed by flow cytometry such as activated T cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.
Measure: Examine the percentage of activated T cells after SCE therapy by flow cytometry Time: 4 weeksDescription: Measurements of immune marker's changes will be preformed by flow cytometry such as the percentage of Th17 cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.
Measure: Assess the percentage of Th17 cells after SCE therapy by flow cytometry Time: 4 weeksDescription: Patients will be monitored for their chest imaging every 3 - 5 days for 4 weeks after receiving SCE therapy.
Measure: Chest imaging changes by computed tomography (CT) scan of the chest Time: 4 weeksDescription: To determine the viral load by real time RT-PCR, samples of blood, sputum, nose / throat swab will be collected from patients during the follow-up studies after receiving SCE therapy.
Measure: Quantification of the SARS-CoV-2 viral load by real time RT-PCR Time: 4 weeksThe scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (SARS-Cov-2) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on SARS-CoV-2 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.
Description: The primary outcome will be the reduction in the incidence of patients requiring intubation and mechanical ventilation, as a marker of deterioration from a mild to a severe form of COVID-19. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.
Measure: Reduction in the incidence of patients with mild/moderate COVID-19 requiring intubation and mechanical ventilation Time: 28 daysDescription: Proportion of deaths from all causes
Measure: Mortality Time: 28 daysDescription: Time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air), alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent) and resolution of hypoxia (defined as SpO2 ≥ 93% in room air or P/F ≥ 300 mmHg). All these improvements must be sustained for 72 hours.
Measure: Time to clinical recovery Time: 28 daysDescription: Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or oropharyngeal swab.
Measure: Negative conversion of COVID-19 RT-PCR from upper respiratory tract Time: 7 daysSevere acute respiratory syndrome (SARS-CoV2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used in as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In-vitro and clinical evidence indicate that inhaled nitric oxide gas (iNO) has also antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. This is a multicenter single-blinded randomized controlled trial with 1:1 individual allocation
Description: Difference within groups in terms of PaO2/FiO2 ratio. If a patient dies during the first 48 hours of treatment, the last available blood gas analysis will be used.
Measure: Change of arterial oxygenation at 48 hours from enrollment Time: 48 hoursDescription: Time to recover gas exchange to a PaO2/FiO2 =/> 300 for at least 24 hours during the first 28 days after enrollment, within each group and comparison between groups. If the patient dies before day 28, the patient will be considered as "never recovered".
Measure: Time to reach normoxemia during the first 28 days after enrollment Time: 28 daysDescription: Daily proportion of patients with a PaO2/FiO2 ratio > 300 for at least 24 hours within each group and comparison between groups. If a patient dies before day 28, the patient will be considered as "never recovered".
Measure: Proportion of SARS-nCoV-2 free patients during the first 28 days after enrollment Time: 28 daysDescription: Proportion of patients surviving at 28 days within each group and comparison between groups.
Measure: Survival at 28 days from enrollment Time: 28 daysDescription: Proportion of patients surviving at 90 days within each group and comparison between groups.
Measure: Survival at 90 days from enrollment Time: 90 daysDescription: Expressed as PaO2/FiO2 ratio within each group and comparison between groups.
Measure: Daily oxygenation in the two groups until day 28 Time: 28 daysDescription: Proportion of patients needing RRT within each group and comparison between groups.
Measure: Need for new renal replacement therapy during the first 28 days Time: 28 daysDescription: Proportion of patients needing (i.e., ECMO, intra-aortic balloon pump, VADs) within each group and comparison between groups.
Measure: Mechanical support of circulation during the first 28 days Time: 28 daysDescription: Average days without need for vasopressors within each group and comparison between groups.
Measure: Days free of vasopressors during the first 28 days Time: 28 daysDescription: Average days without need for mechanical ventilation within each group and comparison between groups.
Measure: Ventilator-free day at 28 days Time: 28 daysDescription: Time to obtain first negative upper respiratory trait sample in the 2019-nCoV rt-PCR assay. Average within groups and comparison between groups.
Measure: Time to SARS-CoV-2 rt-PCR negative in upper respiratory tract specimen Time: 28 daysDescription: Average days out of ICU within each group and comparison between groups.
Measure: ICU-free days at 28 days Time: 28 daysDescription: Average days of ICU admission within each group and comparison between groups.
Measure: ICU length of stay Time: 90 daysIn December 2019 a new kind of virus was identified in China as the responsible of severe acute respiratory syndrome (SARS) and interstitial pneumonia. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread around the world and in February 2020 became a pandemia in Europe. No pharmacological treatment is actually licensed for the SARS-CoV2 infection and at the current state of art there is a lack of data about the clinical management of the coronavirus 2019 disease (COVID-19). The aim of this observational study is to collect the data and the outcomes of COVID-19 patients admitted in the H. Sacco Respiratory Unit treated according to the Standard Operating Procedures and the Good Clinical Practice.
Description: Data collection about the real life management of patients affected by SARS-CoV-2 infection with acute respiratory distress syndrome
Measure: Real life data of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection Time: 1-6 monthsDescription: How many patients died during the hospitalization
Measure: in-hospital mortality Time: 1 monthDescription: How many patients died 30 days after the discharge
Measure: 30 days mortality Time: 1 monthDescription: How many patients died 6 months after the discharge
Measure: 6 months mortality Time: 6 monthsDescription: How many patients were intubated during the hospitalization
Measure: Intubation rate Time: 7 daysDescription: How many days/hours from admittance to intubation
Measure: Time to Intubation Time: 7 daysDescription: How many days/hours from admittance to the start of non invasive ventilation or CPAP therapy
Measure: Time to ventilation Time: 7 daysDescription: How many days/hours from the start of non invasive ventilation or CPAP therapy to the intubation
Measure: Non invasive to Invasive time Time: 7 daysDescription: How many patients were healed from the infection and discharged
Measure: Recovery rate Time: 1 monthDescription: How many patients underwent re-infection after previous recovery from COVID19
Measure: Recurrence rate Time: 1 monthDescription: Assessment of the risk factors for the infection and the admission to the hospital
Measure: Risk factor for COVID19 Time: retrospectiveDescription: What serological parameter could be used as predictor of good or negative prognosis.
Measure: Blood tests and outcome Time: 1 monthDescription: Impact of antiviral therapy on the clinical course of the disease
Measure: Antiviral therapy Time: 1 monthDescription: Assessment of bacterial, fungal or other coinfections rate
Measure: Coinfections Time: 1 monthDescription: Impact of radiological findings on the clinical course and the outcome
Measure: Radiological findings Time: 1 monthDescription: Impact of ultrasound findings on the clinical course and the outcome
Measure: Ultrasound findings Time: 1 monthDescription: Assessment of the evidence of myocardial injury in covid19+ patients
Measure: Myocardial injury Time: 1 monthDescription: impact of standard therapeutic operating procedures (eg enteral nutrition, hydration, drugs) on the clinical course.
Measure: Medical management Time: 1 monthStudy Objective: 1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
Description: Number of participants at 14 days post enrollment with active COVID19 disease.
Measure: Incidence of COVID19 Disease among those who are asymptomatic at baseline Time: 14 daysDescription: Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall change in disease severity over 14 days among those who are symptomatic at baseline Time: 14 daysDescription: Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Measure: Incidence of Hospitalization Time: 14 daysDescription: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Measure: Incidence of Death Time: 90 daysDescription: Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Measure: Incidence of Confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID19 infection.
Measure: Incidence of Symptoms Compatible with COVID19 (possible disease) Time: 90 daysDescription: Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Measure: Incidence of All-Cause Study Medicine Discontinuation or Withdrawal Time: 14 daysDescription: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall symptom severity at 5 and 14 days Time: 5 and 14 daysDescription: Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.
Measure: Ordinal Scale of COVID19 Disease Severity at 14 days among those who are symptomatic at trial entry Time: 14 daysThis is a multi-center, double-blinded study of COVID-19 infected patients randomized 1:1 to daily losartan or placebo for 10 days or treatment failure (hospital admission).
Description: Outcome reported as the number of participants per arm admitted to inpatient hospital care due to COVID-19-related disease within 15 days of randomization. Currently, there is a pre-planned pooled analysis with a national trial network under development.
Measure: Hospital Admission Time: 15 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.
Measure: Change in PROMIS Dyspnea Functional Limitations Time: baseline, 10 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.
Measure: Change in PROMIS Dyspnea Severity Time: baseline, 10 daysDescription: Participants will report their maximum daily oral temperature to the study team. Outcome is reported as the mean maximum daily body temperature (in degrees Celsius) over 10 days.
Measure: Daily Maximum Temperature Time: 10 daysDescription: Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.
Measure: Emergency Department/Clinic Presentations Time: 28 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 7 Time: 7 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 15 Time: 15 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 28 Time: 28 daysDescription: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Oropharyngeal Swab Day 9 Time: 9 daysDescription: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Oropharyngeal Swab Day 15 Time: 15 daysDescription: Outcome reported as the mean number of days participants in each arm did not require ventilator use.
Measure: Ventilator-Free Days Time: 28 daysDescription: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen use.
Measure: Therapeutic Oxygen-Free Days Time: 28 daysDescription: Outcome reported as the percent of participants in each arm who require hospital admission by day 15 following randomization.
Measure: Need for Hospital Admission at 15 Days Time: 15 daysDescription: Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.
Measure: Need for Oxygen Therapy at 15 Days Time: 15 daysNovel Corona Virus (COVID-19) is known to cause Acute Lung Injury/Acute Respiratory Distress Syndrome, that results in death of approximately 80% of those who develop ARDS, despite intensive care and mechanical ventilation. Patients with COVID-19 induced Acute Respiratory Distress Syndrome who are admitted for intensive care including endotracheal intubation and mechanical ventilation will be treated with Aviptadil, a synthetic form of Human Vasoactive Intestinal Polypeptide (VIP) plus maximal intensive care vs. placebo + maximal intensive care. Patients will be randomized to intravenous Aviptadil will receive escalating doses from 50 -150 pmol/kg/hr over 12 hours.
Description: Mortality
Measure: Mortality Time: 5 Days with followup through 30 daysDescription: Index of Respiratory Distress
Measure: PaO2:FiO2 ratio Time: 5 Days with followup through the end of telemetry monitoringDescription: TNF alpha levels as measured in hospital laboratory
Measure: TNF alpha Time: 5 DaysDescription: Multi-system organ failure free days
Measure: Multi-system organ failure free days Time: 5 days with followup through 30 daysThis is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.
Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.
Measure: Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days Time: 7 daysDescription: Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm.
Measure: Daily Hypotensive Episodes Time: 10 daysDescription: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Measure: Hypotension Requiring Vasopressors Time: 10 daysDescription: Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.
Measure: Acute Kidney Injury Time: 10 daysDescription: The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.
Measure: Sequential Organ Failure Assessment (SOFA) Total Score Time: 10 daysDescription: Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.
Measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S) Time: 10 daysDescription: Outcome reported as the number of participants who have expired at 28 days post enrollment.
Measure: 28-Day Mortality Time: 28 daysDescription: Outcome reported as the number of participants who have expired at 90 days post enrollment.
Measure: 90-Day Mortality Time: 90 daysDescription: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Measure: ICU Admission Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
Measure: Number of Ventilator-Free Days Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.
Measure: Number of Therapeutic Oxygen-Free Days Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
Measure: Number of Vasopressor-Free Days Time: 10 daysDescription: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
Measure: Length of ICU Stay Time: 10 daysDescription: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
Measure: Length of Hospital Stay Time: 10 daysDescription: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.
Measure: Incidence of Respiratory Failure Time: 10 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.
Measure: Change in PROMIS Dyspnea Functional Limitations Time: 10 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.
Measure: Change in PROMIS Dyspnea Severity Time: 10 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Time: 10 daysDescription: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Nasopharyngeal Swab Day 9 Time: 9 daysDescription: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Nasopharyngeal Swab Day 15 Time: 15 daysDescription: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Blood Day 9 Time: 9 daysDescription: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Blood Day 15 Time: 15 daysThousands of healthcare workers have been infected with SARS-CoV-2 and contracted COVID-19 despite their best efforts to prevent contamination. No proven vaccine is available to protect healthcare workers against SARS-CoV-2. This study will enroll 470 healthcare professionals dedicated to care for patients with proven SARS-CoV-2 infection. Subjects will be randomized either in the observational (control) group or in the inhaled nitric oxide group. All personnel will observe measures on strict precaution in accordance with WHO and the CDC regulations.
Description: Percentage of subjects with COVID-19 diagnosis in the two groups
Measure: COVID-19 diagnosis Time: 14 daysDescription: Percentage of subjects with a positive test in the two groups
Measure: Positive SARS-CoV-2 rt-PCR test Time: 14 daysDescription: Mean/ Median in the two groups
Measure: Total number of quarantine days Time: 14 daysDescription: Percentage in the two groups
Measure: Proportion of healthcare providers requiring quarantine Time: 14 daysDouble blinded randomized clinical trial designed to evaluate the security and efficacy of hydroxychloroquine as treatment for COVID-19 severe respiratory disease. The investigators hypothesize that a 400mg per day dose of hydroxychloroquine for 10 days will reduce all-cause hospital mortality in patients with severe respiratory COVID-19 disease.
Description: incidence of all-cause mortality
Measure: All-cause hospital mortality Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysDescription: Days from ER admission to hospital discharge
Measure: Length of hospital stay Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysDescription: need of invasive or non invasive mechanical ventilation
Measure: Need of mechanical ventilation Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysDescription: 28 minus days without invasive ventilation support in patients with invasive mechanical ventilation at randomization
Measure: Ventilator free days Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysDescription: Adverse Reactions
Measure: Grade 3-4 adverse reaction Time: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to120 daysThis study is a multi-centre, adaptive, randomized, open clinical trial of the safety and efficacy of treatments for COVID-19 in hospitalized adults. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. Adults (≥18 year-old) hospitalized for COVID-19 with SpO2 ≤ 94% on room air OR acute respiratory failure requiring supplemental oxygen or ventilatory support will be randomized between 4 treatment arms, each to be given in addition to the usual standard of care (SoC) in the participating hospital: SoC alone versus SoC + Remdesivir versus SoC + Lopinavir/Ritonavir versus SoC + Lopinavir/Ritonavir plus interferon ß-1a versus SoC + Hydroxychloroquine. Randomization will be stratified by European region and severity of illness at enrollment (moderate disease: patients NOT requiring non-invasive ventilation NOR high flow oxygen devices NOR invasive mechanical ventilation NOR ECMO and severe disease: patients requiring non-invasive ventilation OR high flow oxygen devices OR invasive mechanical ventilation OR ECMO). The interim trial results will be monitored by a Data Monitoring Committee, and if at any stage evidence emerges that any one treatment arm is definitely inferior then it will be centrally decided that that arm will be discontinued. Conversely, if good evidence emerges while the trial is continuing that some other treatment(s) should also be being evaluated then it will be centrally decided that one or more extra arms will be added while the trial is in progress. The primary objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the control arm in patients hospitalized with COVID-19, the primary endpoint is the subject clinical status (on a 7-point ordinal scale) at day 15.
Description: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.
Measure: Percentage of subjects reporting each severity rating on a 7-point ordinal scale Time: Day 15Description: Time to an improvement of one category from admission on an ordinal scale. Subject clinical status on an ordinal scale at days 3, 5, 8, 11, and 29. Mean change in the ranking on an ordinal scale from baseline to days 3, 5, 8, 11, 15 and 29 from baseline.
Measure: Percentage of subjects reporting each severity rating on a 7-point on an ordinal scale Time: Days 3, 5, 8, 11, 15 and 29Description: • Change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS.
Measure: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Time: Days 3, 5, 8, 11, 15 and 29Description: • Duration of hospitalization (days).
Measure: Hospitalization Time: 29 daysDescription: Rate of mortality
Measure: Mortality Time: In hospital, Day 28, Day 90Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of lopinavir Time: Days 1, 3, 5, 8 and 11Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of hydroxychloroquine Time: Days 1, 3, 5, 8 and 11In the current proposal, the investigators aim to investigate the virological and clinical effects of chloroquine treatment in patients with established COVID-19 in need of hospital admission. Patients will be randomized in a 1:1 fashion to standard of care or standard of care with the addition of therapy with chloroquine.
Description: Viral load assessed by real time polymerase chain reaction in nasopharyngeal samples
Measure: Rate of decline in SARS-CoV-2 viral load Time: Baseline (at randomization) and at 96 hoursDescription: National Early Warning Score score determines the degree of illness of a patient. Scores range from 0-20, with a higher score representing further removal from normal physiology and a higher risk of morbidity and mortality.
Measure: Change in National Early Warning Score score Time: Baseline (at randomization) and at 96 hoursDescription: Transfer from regular ward to intensive care unit during index admission
Measure: Admission to intensive care unit Time: At all times after randomization during index admission (between admission and discharge, approximately 21 days)Description: All-cause mortality during index admission
Measure: In-hospital mortality Time: At all times after randomization during index admission (between admission and discharge, approximately 21 days)Description: Total days admitted to the hospital (difference between admission date and discharge date of index admission)
Measure: Duration of hospital admission Time: During index admission (between admission and discharge, approximately 21 days)Description: All-cause mortality assessed at 30 and 90 days
Measure: Mortality at 30 and 90 days Time: At follow-up 30 and 90 daysDescription: Percentage of subjects reporting each severity rating on a 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: Clinical status Time: 14 days after randomizationThis study aim to evaluate the immune response of negative patients during a COVID-19 outbreak. Patients are serially tested with a VivaDiag ™ COVID-19 lgM / IgG Rapid Test to evaluate the immune response in negative patients and the reliability of the test in those patients who develop clinical signs of COVID-19 during the trial.
Description: Number of patients with negative results in the three measurements, compared to the number of patients with at least one positive test
Measure: Number of patients with constant negative results Time: 30 daysDescription: Number of patients that present at least one positive VivaDiag test that when subsequently tested with PCR remain positive
Measure: Number of patients with positive test with a positive PCR for COVID-19 Time: 30 daysDescription: Where available, number of patients positive for COVID-19 IgG and IgM and positive for COVID-19 PCR
Measure: Overall Number of patients positive for COVID-19 Time: six monthsDescription: Where available, number of patients negative for COVID-19 IgG and IgM and negative for COVID-19 PCR
Measure: Overall Number of patients negative for COVID-19 Time: six monthsDescription: Where available, number of patients positive for COVID-19 IgG and IgM and negative for COVID-19 PCR, or negative for COVID-19 IgG and IgM and positive for COVID-19 PCR
Measure: Number of patients with contrasting results Time: 30 daysDescription: Number of Invalid results
Measure: Reliability of the test Time: 30 daysDescription: Number of healthcare workers that become positive for COVID-19 IgM or IgG
Measure: Positive HCW Time: 60 daysDescription: Number of Chronic Patients that become positive for COVID-19 IgM or IgG
Measure: Number of Chronic Patients Time: 60 daysTriple blinded, phase III randomized controlled trial with parallel groups (200mg of hydroxychloroquine per day vs. placebo) aiming to prove hydroxychloroquine's security and efficacy as prophylaxis treatment for healthcare personnel exposed to COVID-19 patients.
Description: Symptomatic infection rate by COVID-19 defined as cough, dyspnea, fever, myalgia, arthralgias or rhinorrhea along with a positive COVID-19 real-time polymerase chain reaction test.
Measure: Symptomatic COVID-19 infection rate Time: From date of randomization until the appearance of symptoms or study completion 60 days after treatment startDescription: Symptomatic infection rate by other non-COVID-19 viral etiologies defined as cough, dyspnea, fever, myalgia, arthralgias or rhinorrhea along with a positive viral real time polymerase chain reaction test.
Measure: Symptomatic non-COVID viral infection rate Time: From date of randomization until the appearance of symptoms or study completion 60 days after treatment startDescription: Number of days absent from labor due to COVID-19 symptomatic infection
Measure: Days of labor absenteeism Time: From date of randomization until study completion 60 days after treatment startDescription: Absenteeism from labor rate due to COVID-19 symptomatic infection
Measure: Rate of labor absenteeism Time: From date of randomization until study completion 60 days after treatment startDescription: Rate of severe respiratory COVID-19 disease in healthcare personnel
Measure: Rate of severe respiratory COVID-19 disease in healthcare personnel Time: From date of randomization until the appearance of symptoms or study completion 60 days after treatment startModelling repurposed from pandemic influenza is currently informing all strategies for SARS-CoV-2 and the disease COVID-19. A customized disease specific understanding will be important to understand subsequent disease waves, vaccine development and therapeutics. For this reason, ISARIC (the International Severe Acute Respiratory and Emerging Infection Consortium) was set up in advance. This focuses on hospitalised and convalescent serum samples to understand severe illness and associated immune response. However, many subjects are seroconverting with mild or even subclinical disease. Information is needed about subclinical infection, the significance of baseline immune status and the earliest immune changes that may occur in mild disease to compare with those of SARS-CoV-2. There is also a need to understand the vulnerability and response to COVID-19 of the NHS workforce of healthcare workers (HCWs). HCW present a cohort with likely higher exposure and seroconversion rates than the general population, but who can be followed up with potential for serial testing enabling an insight into early disease and markers of risk for disease severity. We have set up "COVID-19: Healthcare worker Bioresource: Immune Protection and Pathogenesis in SARS-CoV-2". This urgent fieldwork aims to secure significant (n=400) sampling of healthcare workers (demographics, swabs, blood sampling) at baseline, and weekly whilst they are well and attending work, with acute sampling (if hospitalised, via ISARIC, if their admission hospital is part of the ISARIC network) and convalescent samples post illness. These will be used to address specific questions around the impact of baseline immune function, the earliest immune responses to infection, and the biology of those who get non-hospitalized disease for local research and as a national resource. The proposal links directly with other ongoing ISARIC and community COVID projects sampling in children and the older age population. Reasonable estimates suggest the usable window for baseline sampling of NHS HCW is closing fast (e.g. baseline sampling within 3 weeks).
Description: Home-isolation or hospital admission
Measure: Seroconversion to SARS-CoV-2 positivity Time: Within 6 monthsCollection and analysis of demographic, clinical, radiographic and laboratory characteristics of CoViD-19 patients to identify predictors of disease severity, mortality and treatment response, and to identify subgroup of patients that might benefit from specific therapeutic interventions
Description: Characterize Patients With SARS-Cov-2 Infection and to Create a Biobank to Identify Predictors of Disease Severity, Mortality and Treatment Response
Measure: Characterize Patients With SARS-Cov-2 Infection and to Create a Biobank to Identify Predictors of Disease Severity, Mortality and Treatment Response Time: Hospital stay (2-3 weeks)The purpose of this study is to test the hypothesis that post-exposure prophylaxis with hydroxychloroquine will reduce the symptomatic secondary attack rate among household contacts of known or suspected COVID-19 patients.
Description: This is defined as either 1. COVID-19 infection confirmed within 14 days of enrollment, following self-report of COVID-19 symptoms to the research study; OR, 2. COVID-19 infection confirmed within 14 days of enrollment, with self-report of COVID-19 symptoms to a treating physician.
Measure: Number of participants with symptomatic, lab-confirmed COVID-19. Time: Date of enrollment to 14 days post-enrollment dateThe investigators plan to carry out an experimental study on the preventive effect of recombinant human interferon alpha nasal drops on the infection of 2019 new coronavirus in medical staff.
Description: new-onset coronavirus disease-2019
Measure: new-onset COVID-19 Time: From date of randomization until the diagnosis of COVID-19, assessed up to 6 weeks.Description: new-onset fever or respiratory symptoms but with negative pulmonary images evidence.
Measure: Number of Participants with coronavirus related symptoms Time: during 28-day intervention.Description: adverse effect of interferon α
Measure: Number of Participants with adverse effect Time: during 28-day intervention.The goal of this study is to evaluate if CT (Computerized Tomography) can effectively and accurately predict disease progression in patients with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). You may be eligible if you have been diagnosed with SARS-CoV-2, are an inpatient at Beaumont Hospital-Royal Oak and meet eligibility criteria. After consent and determination of eligibility, enrolled patients will have a CT scanning session. After the CT scan, patients are followed for 30 days by reviewing their medical records and by phone after discharge from hospital.
Description: Disease progression will be characterized as requiring mechanical ventilator support, non-invasive positive pressure ventilation, high flow nasal cannula or mortality within 30 days.CT-V and PBM scores will be calculated at a voxel level from inhalation-exhalation CT scan. Several CT-V pulmonary function metrics, including the volume of identified "cold spots" (areas with decreased ventilation and perfusion), total ventilation and perfusion and radiographic fibrosis score will be calculated to assess regional ventilation/perfusion and compared to disease progression. The number of participants with correlation between these factors will be reported.
Measure: Predictive association between CT-V, PBM score and disease progression Time: 30 daysSARS-CoV-2, one of a family of human coronaviruses, was initially identified in December 2019 in Wuhan city. This new coronavirus causes a disease presentation which has now been named COVID-19. The virus has subsequently spread throughout the world and was declared a pandemic by the World Health Organisation on 11th March 2020. As of 18 March 2020, there are 198,193 number of confirmed cases with an estimated case-fatality of 3%. There is no approved therapy for COVID-19 and the current standard of care is supportive treatment. SARS-CoV-2 exploits the cell entry receptor protein angiotensin converting enzyme II (ACE-2) to access and infect human cells. The interaction between ACE2 and the spike protein is not in the active site. This process requires the serine protease TMPRSS2. Camostat Mesilate is a potent serine protease inhibitor. Utilizing research on severe acute respiratory syndrome coronavirus (SARS-CoV) and the closely related SARS-CoV-2 cell entry mechanism, it has been demonstrated that SARS-CoV-2 cellular entry can be blocked by camostat mesilate. In mice, camostat mesilate dosed at concentrations similar to the clinically achievable concentration in humans reduced mortality following SARS-CoV infection from 100% to 30-35%.
Description: Clinical improvement defined as live hospital discharge OR a 2 point improvement (from time of enrolment) in disease severity rating on the 7-point ordinal scale
Measure: Cohort 1: Days to clinical improvement from study enrolment Time: 30 daysDescription: Days to clinical improvement from study enrolment defined no fever for at least 48 hrs AND improvement in other symptoms (e.g. cough, expectoration, myalgia, fatigue, or head ache)
Measure: Cohort 2: Days to clinical improvement from study enrolment Time: 30 daysDescription: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Cohort 1: Clinical status as assessed by the 7-point ordinal scale at day 7, 14 and 30 Time: 30 daysDescription: Mortality
Measure: Cohort 1: Day 30 mortality Time: 30 daysDescription: NEWS2
Measure: Cohort 1: Change in NEW(2) score from baseline to day 30 Time: 30 daysDescription: ICU
Measure: Cohort 1: Admission to ICU Time: 30 daysDescription: invasive mechanical ventilation or ECMO
Measure: Cohort 1: Use of invasive mechanical ventilation or ECMO Time: 30 daysDescription: Nasal or high-flow oxygen
Measure: Cohort 1: Duration of supplemental oxygen (days) Time: 30 daysDescription: Subjective clinical improvement
Measure: Cohort 1+2: Days to self-reported recovery (e.g. limitations in daily life activities) during telephone interviews conducted at day 30 Time: 30 daysDescription: No of new COVID-19 infections in the household
Measure: Cohort 2: Number participant-reported secondary infection of housemates Time: 30 daysDescription: Hospital admission
Measure: Cohort 2: Time to hospital admission related to COVID-19 infection Time: 30 daysCOVID-19 has rapidly evolved into a generalized global pandemic. Post-exposure prophylaxis (PEP) against on COVID-19 was identified as an urgent research priority by the WHO, and lopinavir/ritonavir (LPV/r) is a promising candidate for both COVID-19 treatment and PEP, with a good safety profile and global availability. This is a cluster randomized controlled trial (RCT) of oral LPV/r as PEP against COVID-19, that will address the immediate need for preventive interventions, generate key data on COVID-19 transmission, and serve as a research platform for future vaccines and preventive agents.
Description: The primary outcome is microbiologically confirmed COVID-19 infection, ie. detection of viral RNA in a respiratory specimen (mid-turbinate swab, nasopharyngeal swab, sputum specimen, saliva specimen, oral swab, endotracheal aspirate, bronchoalveolar lavage specimen) by day 14 of the study.
Measure: Microbiologic evidence of infection Time: 14 daysDescription: a) Adverse events: as defined using the DAIDS Table for Grading the Severity of Adverse Events, at 7, 14, 28 & 90 days
Measure: Adverse events Time: 90 daysDescription: fever, cough or other respiratory/ systemic symptoms (including but not limited to fatigue, myalgias, arthralgias, shortness of breath, sore throat, headache, chills, coryza, nausea, vomiting, diarrhea) by day 14 in a patient with laboratory confirmed infection, combined with microbiologic confirmation of COVID-19 infection in the participant.
Measure: Symptomatic COVID-19 disease Time: 14 daysDescription: Reactive serology to SARS-CoV-2
Measure: Seropositivity Time: 28 daysDescription: The number of days (or partial days) spent admitted to an acute care hospital will be tabulated both at day 28 and day 90
Measure: Days of hospitalization attributable to COVID-19 disease Time: 90 daysDescription: The number of days (or partial days) requiring i) non-invasive and ii) endotracheal intubation with ventilation will be tabulated both at day 28 and day 90.
Measure: Respiratory failure requiring ventilatory support attributable to COVID-19 disease Time: 90 daysDescription: Death attributable to COVID-19 disease and all-cause mortality
Measure: Mortality Time: 90 daysDescription: Short-term psychological distress will be measured using the K10, with a standard cutoff score of ≥16.
Measure: Short-term psychological impact of exposure to COVID-19 disease Time: 28 daysDescription: Long-term impact will be measured at day 90 using the Impact of Event Scale, a validated measure of traumatic stress response, using a standard cutoff score of ≥26
Measure: Long-term psychological impact of exposure to COVID-19 disease Time: 90 daysDescription: Health-related quality of life will be measured using the EQ-5D-5L (EuroQol-5D). The EQ-5D consists of two pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The tool will be administered to participants at 1, 14, 28 and 90 days.
Measure: Health-related quality of life Time: 90 daysThe Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Around 20% of those infected have severe pneumonia and currently there is no specific or effective therapy to treat this disease. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. But those efforts have not involved large, carefully-conducted controlled studies that would provide the global medical community the proof that these drugs work on a significant scale. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with pneumonia by SARS-CoV2 virus.
Description: Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)
Measure: Evaluation of the clinical status Time: 15 days after randomizationDescription: All-cause mortality rates at 29 days after randomization
Measure: All-cause mortality Time: 29 days after randomizationDescription: Evaluation of the clinical status of patients on the 7th and 29th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)
Measure: Evaluation of the clinical status Time: 7 and 29 days after randomizationDescription: Number of days free from mechanical ventilation at 29 days after randomization
Measure: Number of days free from mechanical ventilation Time: 29 days after randomizationDescription: Number of days that the patient was on mechanical ventilation after randomization
Measure: Duration of mechanical ventilation Time: 7, 15 and 29 days after randomizationDescription: Length of hospital stay on survivors
Measure: Duration of hospitalization Time: 7, 15 and 29 days after randomizationDescription: Presence of other secondary infections
Measure: Other secondary infections Time: 7, 15 and 29 days after randomizationDescription: Time from treatment start to death
Measure: Time from treatment start to death Time: 7, 15 and 29 days after randomizationDescription: Occurrence of QT interval prolongation
Measure: QT interval prolongation Time: 7, 15 and 29 days after randomizationDescription: Occurrence of gastrointestinal intolerance
Measure: Gastrointestinal intolerance Time: 7, 15 and 29 days after randomizationDescription: Occurrence of laboratory albnormalities in red blood cell count, creatinine and bilirubin
Measure: Laboratory albnormalities Time: 7, 15 and 29 days after randomizationDescription: Occurrence of adverse events related to the use of the investigational products
Measure: Adverse events Time: 7, 15 and 29 days after randomizationThe (World Health Organization) WHO NOR- (Coronavirus infectious disease) COVID 19 study is a multi-centre, adaptive, randomized, open clinical trial to evaluate the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in hospitalized adult patients diagnosed with COVID-19. This trial will follow the core WHO protocol but has additional efficacy, safety and explorative endpoints.
Description: All cause in-hospital mortality
Measure: In-hospital mortality Time: 3 weeksCoronavirus (COVID-19) is a somewhat new and recognized infectious disease that is now spreading to several countries in the world, including Brazil. Hydroxychloroquine and azithromycin may be useful for treating those patients. COALITION I study aims to compared standard of care, hydroxychloroquine plus azithromycin and hydroxychloroquine monotherapy for treatment of hospitalized patients with COVID-19. COALITION I will recruit 630 patients with infection by COVID-19 (210 per arm). Ordinal endpoint of status at 15 days will be the primary endpoint.
Description: Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 7 points. Alive at home without limitations on activities Alive at home without limitations on activities In the hospital without oxygen In the hospital using oxygen In the hospital using high-flow nasal catheter or non-invasive ventilation In hospital, on mechanical ventilation Dead
Measure: Evaluation of the clinical status Time: 15 days after randomizationDescription: Evaluation of the clinical status of patients on the 7th day after randomization defined by the Ordinal Scale of 7 points. Alive at home without limitations on activities Alive at home without limitations on activities In the hospital without oxygen In the hospital using oxygen In the hospital using high-flow nasal catheter or non-invasive ventilation In hospital, on mechanical ventilation Dead
Measure: Ordinal scale in 7 days Time: 7 days after randomizationDescription: Need of intubation and mechanical ventilation up to the 7th day after randomization
Measure: Need of intubation and mechanical ventilation Time: 7 days after randomizationDescription: Use of mechanical ventilation during hospital stay
Measure: Use of mechanical ventilation during hospital stay Time: 15 days after randomizationDescription: Use of non-invasive ventilation up to the 7th day after randomization
Measure: Use of non-invasive ventilation Time: 7 days after randomizationDescription: Hospital Length of Stay
Measure: Hospital Length of Stay Time: 28 days after randomizationDescription: All-cause mortality rates during hospital stay
Measure: All-cause mortality Time: 28 days after randomizationDescription: Occurrence of thromboembolic complications such as: Deep vein thrombosis Pulmonary Embolism Stroke
Measure: Thromboembolic complications Time: 15 days after randomizationDescription: Occurrence of renal dysfunction, defined as an increase in creatinine above 1.5 times the baseline value
Measure: Acute renal disfunction Time: 15 days after randomizationDescription: Number of days alive and free of respiratory support up to 15 days (DAFOR15), defined as the sum of days patients did not require supplementary oxygen, non-invasive ventilation, high-flow nasal catheter neither mechanical ventilation at 15 -days. Patients that perished during the 15-day window will receive zero DAFOR15.
Measure: Number of days alive and free of respiratory support up to 15 days Time: 15 daysDescription: Corrected QT interval
Measure: Safety outcome on corrected QT interval Time: At day 3 and 7 after enrollmentThis observational study will collect data from patients treated under a compassionate use programme with siltuximab (SYLVANT); patients diagnosed with COVID-19 infection who have developed serious respiratory complications. This observational study will group the patients into two cohorts receiving siltuximab. Patients in Cohort A are treated in a non-ICU setting and patients in Cohort B are in an ICU setting. Each patient will have a matched control receiving standard treatment without siltuximab
Description: reduction of the need of invasive ventilation or 30-day mortality
Measure: Cohort A: reduction of the need of invasive ventilation or 30-day mortality Time: 30 daysDescription: reduction of mortality
Measure: Cohort B: reduction of mortality Time: 30 daysIn December 2019,a new type of pneumonia caused by the coronavirus (COVID-2019) broke out in Wuhan ,China, and spreads quickly to other Chinese cities and 28 countries. More than 70000 people were infected and over 2000 people died all over the world. There is no specific drug treatment for this disease. Considering that lung damage is related to both viral infection and burst of cytokines, our idea is to evaluate the efficacy and safety of escin as add-on treatment to conventional antiviral drugs in COVID-19 infected patients.
Description: All cause mortality
Measure: Mortality rate Time: up to 30 daysDescription: mild type:no No symptoms, Radiological examination: no pneumonia; possible mild increase in C-reactive portein 2, moderate type: fever, cough, or other respiratory symptoms. Radiological examination: pneumonia, SpO2>93% without oxygen inhalation ; increase in C reactive protein, 3: severe type: a. Rate ≥30bpm;b. Pulse Oxygen Saturation (SpO2)≤93% without oxygen inhalation,c. PaO2/FiO2(fraction of inspired oxygen )≤300mmHg ;4. Critically type:match any of the follow: a. need mechanical ventilation; b. shock; c. (multiple organ dysfunction syndrome) MODS
Measure: Clinical status evaluated in agreement with guidelines Time: up to 30 daysDescription: Pulse Oxygen Saturation(SpO2)>93%,1. No need for supplemental oxygenation; 2. nasal catheter oxygen inhalation(oxygen concentration%,The oxygen flow rate:L/min);3. Mask oxygen inhalation(oxygen concentration%,The oxygen flow rate:L/min);4. Noninvasive ventilator oxygen supply(Ventilation mode,oxygen concentration%,The oxygen flow rate:L/min,);5. Invasive ventilator oxygen supply(Ventilation mode,oxygen concentration%,The oxygen flow rate:L/min,)
Measure: The differences in oxygen intake methods Time: up to 30 daysDescription: days
Measure: Time of hospitalization (days) Time: up to 30 daysDescription: days
Measure: Time of hospitalization in intensive care units Time: up to 30 daysDescription: forced expiratory volume at one second ,maximum voluntary ventilation at 1month,2month,3month after discharge
Measure: Pulmonary function Time: up to 3 months after dischargeThis study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine.
Description: The patient will becategorized into one of the following 8 categories depending on status of their hospitalization: Dead (yes/no) Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) (yes/no) Hospitalized and receiving Non-invasive ventilation or "high-flow oxygen device" (yes/no) Hospitalized and given oxygen supplements different from (2) and (3) (yes/no) Hospitalized and without oxygen treatment, but receiving other treatment (both related to COVID-19 or other) (yes/no) Hospitalized for observation (yes/no) Discharged from hospital with restriction of activity level (yes/no) Discharged from hospital without any restrictions of activity level (yes/no) Only one category can be "yes".
Measure: Categorization of hospitalization status Time: 14 daysDescription: Delta PaO2 measured in arterial puncture
Measure: Change in patient's oxygen partial pressure Time: 4 daysDescription: Delta PaCO2 measured in arterial puncture
Measure: Change in patient's carbondioxid partial pressure Time: 4 daysDescription: pH measured in arterial puncture
Measure: Level of pH in blood Time: 4 daysCytokines and chemokines are thought to play an important role in immunity and immunopathology during virus infections [3]. Patients with severe COVID-19 have higher serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8) compared to individuals with mild disease or healthy controls, similar to patients with SARS or MERS . The change of laboratory parameters, including elevated serum cytokine, chemokine levels, and increased NLR in infected patients are correlated with the severity of the disease and adverse outcome, suggesting a possible role for hyper-inflammatory responses in COVID-19 pathogenesis. Importantly, previous studies showed that viroporin E, a component of SARS-associated coronavirus (SARS-CoV), forms Ca2C-permeable ion channels and activates the NLRP3 inflammasome. In addition, another viroporin 3a was found to induce NLRP3 inflammasome activation . The mechanisms are unclear. Colchicine, an old drug used in auto-inflammatory disorders (i.e., Familiar Mediterranean Fever and Bechet disease) and in gout, counteracts the assembly of the NLRP3 inflammasome, thereby reducing the release of IL-1b and an array of other interleukins, including IL-6, that are formed in response to danger signals. Recently, colchicine has been successfully used in two cases of life-threatening post-transplant capillary leak syndrome. These patients had required mechanically ventilation for weeks and hemodialysis, before receiving colchicine, which abruptly restored normal respiratory function and diuresis over 48 hrs [4].
Description: Time to clinical improvement: defined as time from randomization to an improvement of two points from the status at randomization on a seven-category ordinary scale
Measure: Clinical improvement Time: Day 28Description: Live discharge from the hospital (whatever comes first)
Measure: Hospital discharge Time: Day 28Description: Number of death patients
Measure: Death Time: Day 28Description: 7-category ordinal scale
Measure: Clinical status Time: Day 7, Day 14Description: Number of patients with mechanical ventilhation
Measure: Mechanical ventilhation Time: Day 28Description: Days of hospitalization
Measure: Hospitalization Time: Day 28Description: Days to death from treatment initiation
Measure: Time from treatment initiation to death Time: Day 28Description: negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart
Measure: Time to Negativization COVID 19 Time: Day 21Description: Time to remission of fever in patients with T>37.5°C at enrollment
Measure: Fever Time: Day 1,4,7,14,21,28This is a phase 3, multi-center, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of colchicine in adult patients diagnosed with COVID-19 infection and have at least one high-risk criterion. Approximately 6000 subjects meeting all inclusion and no exclusion criteria will be randomized to receive either colchicine or placebo tablets for 30 days.
Description: The primary endpoint will be the composite of death or the need for hospitalization due to COVID-19 infection in the first 30 days after randomization.
Measure: Number of participants who die or require hospitalization due to COVID-19 infection Time: 30 days post randomizationDescription: The secondary endpoint is the occurrence of death in the 30 days following randomization.
Measure: Number of participants who die Time: 30 days post randomizationDescription: The secondary endpoint is the need for hospitalization due to COVID-19 infection in the 30 days following randomization.
Measure: Number of participants requiring hospitalization due to COVID-19 infection Time: 30 days post randomizationDescription: The secondary endpoint is the need for mechanical ventilation in the 30 days following randomization.
Measure: Number of participants requiring mechanical ventilation Time: 30 days post randomizationIn December 2019, the Municipal Health Committee of Wuhan, China, identified an outbreak of viral pneumonia of unknown cause. This new coronavirus was called SARS-CoV-2 and the disease caused by that virus, COVID-19. Recent numbers show that 222,643 infections have been diagnosed with 9115 deaths, worldwide. Currently, there are no approved therapeutic agents available for coronaviruses. In this scenario, the situation of a global public health emergency and evidence about the potential positive effect of chloroquine (CQ) in most coronaviruses, including SARS-CoV-1, and recent data on small trials on SARS-CoV-2, the investigators intend to investigate the efficacy and the safety of CQ diphosphate in the treatment of hospitalized patients with severe acute respiratory syndrome in the scenario of SARS-CoV2. Preliminary in vitro studies and uncontrolled trials with low number of patients of CQ repositioning in the treatment of COVID-19 have been encouraging. The main hypothesis is that CQ diphosphate will reduce mortality in 50% in those with severe acute respiratory syndrome infected by the SARS-COV2. Therefore, the main objective is to assess whether the use of chloroquine diphosphate reduces mortality by 50% in the study population. The primary outcome is mortality in day 28 of follow-up. According to local contingency plan, developed by local government for COVID-19 in the State of Amazonas, the Hospital Pronto-Socorro Delphina Aziz, located in Manaus, is the reference unit for the admission of serious cases of the new virus. The unit currently has 50 ICU beds, with the possibility of expanding to 335 beds, if needed. The hospital also has trained multiprofessional human resources and adequate infrastructure. In total, 440 participants (220 per arm) will receive either high dose chloroquine 600 mg bid regime (4x150 mg tablets, every 12 hours, D1-D10) or low dose chloroquine 450mg bid regime (3x150mg tablets + 1 placebo tablet every 12 hours on D1, 3x150mg tablets + 1 placebo followed by 4 placebo tablets 12h later from D2 to D5, and 4 placebo tablets every 12 hours, D6-D10). Placebo tablets were used to standardize treatment duration and blind research team and patients. All drugs administered orally (or via nasogastric tube in case of orotracheal intubation). Both intervention and placebo drugs will be produced by Farmanguinhos. Clinical and laboratory data during hospitalization will be used to assess efficacy and safety outcomes.
Description: proportion of deaths at day 28 between groups compared
Measure: Mortality rate reduction of 50% by day 28 Time: 28 days after randomizationDescription: number of deaths at days 7 and 14 between groups compared
Measure: Absolute mortality on days 7 and 14 Time: 7 and 14 days after first doseDescription: clinical status
Measure: Improvement in overall subject's clinical status assessed in standardized clinical questionnaires on days 14 and 28 Time: 14 and 28 days after first doseDescription: clinical status
Measure: Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization Time: during and after intervention, up to 28 daysDescription: supplemental oxygen
Measure: Duration of supplemental oxygen (if applicable) Time: during and after intervention, up to 28 daysDescription: mechanical ventilation
Measure: Duration of mechanical ventilation (if applicable) Time: during and after intervention, up to 28 daysDescription: hospitalization
Measure: Absolute duration of hospital stay in days Time: during and after intervention, up to 28 daysDescription: adverse events grade 3 and 4
Measure: Prevalence of grade 3 and 4 adverse events Time: during and after intervention, up to 28 daysDescription: adverse events
Measure: Prevalence of serious adverse events Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum creatinine compared to baseline
Measure: Change in serum creatinine level Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum troponin I compared to baseline
Measure: Change in serum troponin I level Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum aspartate aminotransferase compared to baseline
Measure: Change in serum aspartate aminotransferase level Time: during and after intervention, up to 28 daysDescription: increase or decrease in serum aspartate aminotransferase compared to baseline
Measure: Change in serum CK-MB level Time: during and after intervention, up to 28 daysDescription: virus clearance from respiratory tract secretion
Measure: Change in detectable viral load in respiratory tract swabs Time: during and after intervention, up to 28 daysDescription: viremia in blood detected through RT-PCR
Measure: Viral concentration in blood samples Time: during and after intervention, up to 28 daysDescription: death
Measure: Absolute number of causes leading to participant death (if applicable) Time: during and after intervention, up to 28 daysCOVID-19 infection is overwhelming Italian healthcare. There is an urgent need for a solution to the lack of ICU beds and increasing deaths day after day. A recent retrospective Chinese paper (JAMA Intern Med, online March 13, 2020) showed impressive positive effect of methylprednisolone (MP) on survival of SARS-CoV-2 critically ill patients. We're routinely using MP for severe pneumonia-ARDS with acute respiratory failure with very good results. The main objective of this multi-centre observational trial is to evaluate the efficacy of low dose prolonged infusion of methylprednisolone (MP) for patients with severe acute respiratory syndrome.
Description: Death or ICU admission or Invasive mechanical ventilation (yes/not, at least one of three of the composite end-point)
Measure: Composite primary end-point Time: 28 daysDescription: Yes/no
Measure: death Time: 28 daysDescription: yes/no
Measure: Admission to ICU Time: 28 daysDescription: yes/no
Measure: Endotracheal intubation (invasive mechanical ventilation) Time: 28 daysDescription: mg/L
Measure: reduction of C-reactive protein or CRP Time: 14 days and 28 daysDescription: number of days free from mechanical ventilation (invasive or not)
Measure: Reduction of mechanical ventilation Time: 28 daysThe overall objective of the study is to determine which treatments (e.g. immune modulator drugs) have the most favorable benefit-risk in adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. The specific aims of this Covid19 cohort are to collect observational data at regular intervals on an ongoing basis in order to embed a series of randomized controlled trials evaluating a various set of interventions for patients with COVID-19 pneumonia. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design.
Description: Overall Survival
Measure: Survival Time: 14 daysDescription: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale COVID 19 Time: 14 daysThe overall objective of the study is to determine the therapeutic effect and tolerance of Sarilumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Sarilumab is a human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound IL-6Rs (sIL-6Rα and mIL-6Rα) and has been shown to inhibit IL-6-mediated signaling through these receptors. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Sarilumab administration to patients enrolled in the CORIMUNO-19 cohort. Sarilumab will be administered to consenting adult patients hospitalized with COVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Sarilumab will receive standard of care. Outcomes of Sarilumab-treated patients will be compared with outcomes of standard of care-treated patients as well as with outcomes of patients treated with other immune modulators.
Description: Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measure: Survival without needs of ventilator utilization at day 14. Time: 14 daysDescription: Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale <=5 at day 4 Time: 4 daysDescription: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 Time: 14 daysDescription: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event. Scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9
Measure: WHO progression scale at day 4 Time: 4 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale Time: 7 and 14 daysDescription: Overall survival
Measure: Survival Time: 14, 28 and 90 daysDescription: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
Measure: respiratory acidosis at day 4 Time: 4 daysDescription: evolution of PaO2/FiO2 ratio
Measure: PaO2/FiO2 ratio Time: day 1 to day 14Description: time to oxygen supply independency
Measure: time to oxygen supply independency Time: 14 daysDescription: duration of hospitalization
Measure: duration of hospitalization Time: 90 daysDescription: time to negative viral excretion
Measure: time to negative viral excretion Time: 90 daysDescription: time to ICU discharge
Measure: time to ICU discharge Time: 90 daysDescription: time to hospital discharge
Measure: time to hospital discharge Time: 90 daysACT is a randomized clinical trial to assess therapies to reduce the clinical progression of COVID-19.
Description: In outpatients with COVID-19, the occurrence of hospital admission or death
Measure: Outpatients: Hospital Admission or Death Time: Up to 6 weeks post randomizationDescription: Patients intubated or requiring imminent intubation at the time of randomization will only be followed for the primary outcome of death.
Measure: Inpatients: Invasive mechanical ventilation or mortality Time: Up to 6 weeks post randomizationIn December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. Our primary goal is to investigate the efficacy of treatment with a CytoSorb® adsorber in patients with severe COVID-19 disease requiring venous ECMO over 72 hours after initiation of ECMO. The primary endpoint is the reduction of plasma interleukin-6 levels 72 hours after initiation of ECMO support. As secondary endpoints we investigate 30-day survival, vasopressor and volume requirements, lactate in terms of lactate and platelet function. As safety variables, we further investigate the levels of the applied antibiotics (usually ampicillin and sulbactam).
Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)
Measure: interleukin-6 (IL-6) level after 72 hours Time: 72 hoursDescription: survival after 30 days
Measure: 30-day-survival Time: 72 hoursDescription: needed dosage of norepinephrine and other vasopressors
Measure: vasopressor dosage Time: 72 hoursDescription: fluid balance levels during cytokine adsorption
Measure: fluid balance Time: 72 hoursDescription: serum-lactate levels during cytokine adsorption
Measure: lactate Time: 72 hoursThis study will assess the prevalence and incidence of COVID-19 infection in patients with chronic plaque psoriasis on immunosuppressant therapy.
Study on adult patients positive to COVID-19 virus. After signing informed consent and undergoing screening assessments, eligible patients will record few times a day several pre-defined sentences to the Cordio App installed in a smartphone/tablet. The app will upload the vocal data to the sponsor's servers for analysis. The patient will record at hospital admittance (COVID-19 positive) until patient defined as COVID-19 negative and free of relevant clinical symptoms.
Description: patient voice that is recorded during the study will be anylaysis with specific algorithms
Measure: Voice anaysis Time: 1-2 yearsOn January 2020, the discovery of a new coronavirus (SARS-CoV-2) was officially announced by the Chinese health authorities and the World Health Organization (WHO). Its complete genome was sequenced by the laboratory of respiratory infection viruses at the Institut Pasteur on 29 January 2020 in France. This will allow the identification of antigenic structures involved in the immune response and the development of serological diagnostic tests. Many questions are being asked about this new virus and the infection it causes, including questions about the percentage of asymptomatic and pauci-symptomatic forms. Serological studies can provide answers to these questions. There is no serological test for SARS-COV-2 yet, but the laboratory of respiratory infection viruses at the Institut Pasteur is working on its development. This study proposes to carry out a collection of samples taken from subjects who travelled to China before the epidemic outbreak or suspected of being infected with SARS-CoV-2. As soon as it is available, serology will be performed on the collected samples.
Description: Description of the serological status of individuals by different detection tests
Measure: Presence of specific anti-SARS-CoV-2 antibodies in the different study groups. Time: One yearDescription: Proportion of asymptomatic subjects into seropositive population
Measure: Percentage of asymptomatic forms in individuals with anti-SARS-CoV-2 antibodies Time: One yearCoronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and had subsequently spread worldwide. Twenty-nine percent of COVID-19 patients may develop ARDS. Based on the potential beneficial mechanisms of HFNC and PP, whether early use of prone positioning combined with HFNC can avoid the need for intubation in COVID-19 induced moderate to severe ARDS patients needs to be further investigated.
Description: the treatment failure rate of HFNC/HFNC+PP support and clinical requirement for advanced respiratory support
Measure: Treatment failure Time: 28 daysDescription: the improvement of SpO2/FIO2 or PaO2/FiO2 from HFNC alone to HFNC+PP
Measure: Efficacy of PP Time: 28 daysCOVID-19 may cause another world-wide epidemic. This study is divided into 2 arms: (1) Prospective longitudinal observational study involving patients with laboratory-confirmed COVID-19 and (2) Retrospective study on patients with laboratory-confirmed COVID-19. Arm 1: We will collect EDTA blood, stool samples, rectal swab, urine, saliva, and specimens from upper respiratory tract (nasopharyngeal aspirate or flocked swab), and lower respiratory tract (sputum or tracheal aspirate) on daily, alternate day, or weekly basis as appropriate. Arm 2: The remainder of specimens that were submitted for laboratory investigation as part of clinical management will be retrieved. Those specimens will only be used after all clinically indicated testing and confirmation procedures have been completed. Assistance from the Public Health Laboratory Service, Department of Health, will be invited to retrieve samples as well as participate in this study. Patients hospitalized for pneumonia in medical wards and ICU at the Prince of Wales Hospital tested negative for COVID-19 will be recruited as controls. Understanding the clinical, virological, microbiological and immunological profiles of this infection is urgently needed to facilitate its management and control.
Description: Patients' treatment and management during hospitalization.
Measure: Clinical Time: 6 monthsDescription: Serial viral load changes during hospitalization.
Measure: Virological Time: 6 monthsDescription: Alterations in fecal microbiota composition (including virome, bacteria and fungi) in COVID-19 patients compared with healthy controls.
Measure: Microbiological Time: 6 monthsCOVID-19 Viral Global Pandemic resulting in post-infection pulmonary damage, including Fibrotic Lung Disease due to inflammatory and reactive protein secretions damaging pulmonary alveolar structure and functionality. A short review includes: - Early December, 2019 - A pneumonia of unknown cause was detected in Wuhan, China, and was reported to the World Health Organization (WHO) Country Office. - January 30th, 2020 - The outbreak was declared a Public Health Emergency of International Concern. - February 7th, 2020 - 34-year-old Ophthalmologist who first identified a SARS-like coronavirus) dies from the same virus. - February 11th, 2020 - WHO announces a name for the new coronavirus disease: COVID-19. - February 19th, 2020 - The U.S. has its first outbreak in a Seattle nursing home which were complicated with loss of lives.. - March 11th, 2020 - WHO declares the virus a pandemic and in less than three months, from the time when this virus was first detected, the virus has spread across the entire planet with cases identified in every country including Greenland. - March 21st, 2020 - Emerging Infectious Disease estimates the risk for death in Wuhan reached values as high as 12% in the epicenter of the epidemic and ≈1% in other, more mildly affected areas. The elevated death risk estimates are probably associated with a breakdown of the healthcare system, indicating that enhanced public health interventions, including social distancing and movement restrictions, should be implemented to bring the COVID-19 epidemic under control." March 21st 2020 -Much of the United States is currently under some form of self- or mandatory quarantine as testing abilities ramp up.. March 24th, 2020 - Hot spots are evolving and identified, particularly in the areas of New York-New Jersey, Washington, and California. Immediate attention is turned to testing, diagnosis, epidemiological containment, clinical trials for drug testing started, and work on a long-term vaccine started. The recovering patients are presenting with mild to severe lung impairment as a result of the viral attack on the alveolar and lung tissues. Clinically significant impairment of pulmonary function appears to be a permanent finding as a direct result of the interstitial lung damage and inflammatory changes that accompanied. This Phase 0, first-in-kind for humans, is use of autologous, cellular stromal vascular fraction (cSVF) deployed intravenously to examine the anti-inflammatory and structural potential to improve the residual, permanent damaged alveolar tissues of the lungs.
Description: Reporting of Adverse Events or Severe Adverse Events Assessed by CTCAE v4.0
Measure: Incidence of Treatment-Emergent Adverse Events Time: 1 monthDescription: High Resolution Computerized Tomography of Lung (HRCT Lung) for Fluidda Analysis comparative at baseline and 3 and 6 months post-treatment comparative analytics
Measure: Pulmonary Function Analysis Time: baseline, 3 Month, 6 monthsDescription: Finger Pulse Oximetry taken before and after 6 minute walk on level ground, compare desaturation tendency
Measure: Digital Oximetry Time: 3 months, 6 monthsAn open access study that will define and collect digital measures of coughing in multiple populations and public spaces using various means of audio data collection.
Description: Size of collected audio dataset measured as number of collected cough sounds, targeting ≥10,000 identified coughs.
Measure: Dataset size Time: 14 daysDescription: Identification of cough sounds by the existing mathematical model with ≥ 99% specificity and ≥ 60% sensitivity
Measure: Cough sound identification Time: 14 daysDescription: Increase in the sensitivity of the mathematical model to cough sounds to ≥ 70% while retaining the specificity of ≥ 99%
Measure: Improvement of the existing model Time: 14 daysDescription: Determination of the level of acceptance and satisfaction of the solution by patients by means of a Standard Usability Questionnaire to provide feedback. The score ranges from 10 to 50, higher score indicating a better usability.
Measure: Evaluate the usability of the application Time: 14 days7. Objectives To apply e-health methods to perform active monitoring and assess determinants of incident Infection of COVID-19 in a hospital population. 8. Study design Prospective, Single-centre, observational clinical study. 9. Disease or disorder under study Healthy people in risk of COVID-19 infection. 10. Main variable. Symptoms related to infection caused by SARS-Cov2. 11. Study population and total number of patients Men and women in general god health status aged between 18 and 80 years that currently are employees of Hospital de La Princesa . 12. Duration of treatment Each subject will be monitored, since its recruitment, for a period of 12 weeks. 13. Timetable and expected date of completion The overall duration of the study is estimated at about 6 months, from patient recruitment to the last data recorded by last subject. The aim is to carry out this study from March 2020 onwards.
Description: The primary objective of this trial is to investigate whether the use of a cell phone App-based platform is a useful tool to monitor the symptoms of a population in risk of SARS-Cov2 infection. The final aim is to assess determinants of incidence of infection of COVID-19 in people working in Hospital during the pandemia of SARS-Cov-2.
Measure: COVID-19 App-based platform Time: 6 monthsDescription: To monitor in real-time COVID-19 symptoms in the hospital workforce, which are a proxy of incident infection (Step 1) To identify in real-time clusters of COVID-19 symptoms and to facilitate control measures. To determine the incidence of new infection of COVID-19. To identify the determinants and risk/protective factors associated with this infection, in a workforce hospital population free of COVID-19 at the start of our study.
Measure: COVID-19 infection Time: 6 monthsThis is a randomized, double-blind placebo-controlled trial to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-19 infection. On evaluation for enrollment, participant will need to meet all inclusion and exclusion criteria. If participant consents, they will be randomized 1:1 to treatment with either tradipitant 85 mg PO BID or placebo in addition to standard of care for COVID-19 infection as per the protocol at the treating hospital. NEWS 2 will be assessed at screening and daily following randomization. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.
This study will utilize a single center internal control study design. The objective of this study is to determine the feasibility and safety of a bidirectional oxygenation PEEP generating mouthpiece when combined with oxygen by non-rebreather face mask, compared to support by oxygen non-rebreather face mask alone.
Description: The primary endpoint for this feasibility study is pulse oximetry level after treatment with a Bidirectional Oxygenation Valve
Measure: Pulse oximetry level Time: Change from Baseline pulse oximetry level at 15 minutes post treatmentDescription: Venous and arterial blood gases, if available, will be combined to report systemic carbon dioxide.
Measure: Systemic carbon dioxide Time: Change from Baseline clinical measurements at 15 minutes post treatmentHealthcare professionals mainly doctors, nurses and their first degree relatives (spouse, father, mother, sister, brother, child) who have been started hydroxychloroquine(plaquenil) 200mg single dose repeated every three weeks plus vitaminC including zinc once a day were included in the study. Study has conducted on 20th of march. Main purpose of the study was to cover participants those who are facing or treating COVID19 infected patients in Ankara.
Description: persons who took this medication should not have an infection
Measure: Protection against COVID-19 Time: 4 monthsPhase III, two-group multicentre, randomised controlled trial in up to 10 078 healthcare workers to determine if BCG vaccination reduces the incidence and severity of COVID-19 during the 2020 pandemic.
Description: Number of participants with COVID-19 disease defined as positive SARS-Cov-2 test (PCR or serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Measure: COVID-19 disease incidence Time: Measured over the 6 months following randomisationDescription: Number of participants with severe COVID-19 disease, defined as: COVID-19 disease with hospitalisation, death, or non-hospitalised severe disease. Non-hospitalised severe disease is defined as non-ambulant (*) for ≥ 3 consecutive days OR unable to work (**) for ≥ 3 consecutive days. (*) "pretty much confined to bed (meaning finding it very difficult to do any normal daily activities". (**) "I do not feel physically well enough to go to work"
Measure: Severe COVID-19 disease incidence Time: Measured over the 6 months following randomisationDescription: Number of participants with COVID-19 disease defined as positive SARS-Cov-2 test (PCR or serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Measure: COVID-19 incidence by 12 months Time: Measured over the 12 months following randomisationDescription: Number of participants with severe COVID-19 disease, defined as: COVID-19 disease with hospitalisation, death, or non-hospitalised severe disease. Non-hospitalised severe disease is defined as non-ambulant(*) for ≥ 3 consecutive days OR unable to work (**) for ≥ 3 consecutive days. * "pretty much confined to bed (meaning finding it very difficult to do any normal daily activities" ** "I do not feel physically well enough to go to work"
Measure: Severe COVID-19 incidence by 12 months Time: Measured over the 12 months following randomisationDescription: Time to first symptom of COVID-19 in a participant who subsequently meets the case definition: positive SARS-Cov-2 test (PCR or serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Measure: Time to first symptom of COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of episodes of COVID-19 disease defined as positive SARS-Cov-2 test (PCR or serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Measure: Episodes of COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of participants with asymptomatic SARS-CoV-2 infection defined as Evidence of SARS-CoV-2 infection (by PCR or seroconversion) Absence of respiratory illness (using self-reported questionnaire) No evidence of exposure prior to randomisation (inclusion serology negative)
Measure: Asymptomatic SARS-CoV-2 infection Time: Measured over the 12 months following randomisationDescription: Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to COVID-19 disease defined as positive SARS-Cov-2 test (PCR or serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Measure: Work absenteeism due to COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of days confined to bed (using self-reported questionnaire) due to COVID-19 disease defined as positive SARS-Cov-2 test (PCR or serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Measure: Bed confinement due to COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of days with symptoms in any episode of illness that meets the case definition for COVID-19 disease: positive SARS-Cov-2 test (PCR or serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)
Measure: Symptom duration of COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: SARS-CoV-2 pneumonia Time: Measured over the 12 months following randomisationDescription: Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: Oxygen therapy with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: Critical care admissions with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of days admitted to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test
Measure: Critical care admission duration with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
Measure: Mechanical ventilation with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of days that participants needed mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test
Measure: Mechanical ventilation duration with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of days of hospitalisation due to COVID-19 (using self-reported questionnaire and/or medical/hospital records).
Measure: Hospitalisation duration with COVID-19 Time: Measured over the 12 months following randomisationDescription: Number of deaths (from death registry) associated with a positive SARS-CoV-2 test
Measure: Mortality with SARS-CoV-2 Time: Measured over the 12 months following randomisationDescription: Number of participants with fever or respiratory illness will be defined as: fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Fever or respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of episodes of fever or respiratory illness, defined as fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Episodes of fever or respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to fever or respiratory illness defined as fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Work absenteeism due to fever or respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of days confined to bed (using self-reported questionnaire) due to fever or respiratory illness defined as fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Bed confinement due to fever or respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of days with symptoms in any episode of illness that meets the case definition for fever or respiratory illness: fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)
Measure: Symptom duration of fever or respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records)
Measure: Pneumonia Time: Measured over the 12 months following randomisationDescription: Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records)
Measure: Oxygen therapy Time: Measured over the 12 months following randomisationDescription: Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records)
Measure: Critical care admissions Time: Measured over the 12 months following randomisationDescription: Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)
Measure: Mechanical ventilation Time: Measured over the 12 months following randomisationDescription: Number of deaths (from death registry)
Measure: Mortality Time: Measured over the 12 months following randomisationDescription: Number of days of hospitalisation due to fever or respiratory illness (using self-reported questionnaire, medical/hospital records and/or government registries)
Measure: Hospitalisation duration with fever or respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of days of unplanned absenteeism for any reason (using self-reported questionnaire)
Measure: Unplanned work absenteeism Time: Measured over the 12 months following randomisationDescription: Cost of hospitalisation due to COVID-19 will be reported and compared between groups (using hospital administrative linked costing records held by individual hospitals and state government routine costing data collections to provide an estimate of the cost to hospitals for each episode of COVID-19 care)
Measure: Hospitalisation cost to treat COVID-19 Time: Measured over the 12 months following randomisationDescription: Type and severity of local and systemic adverse events will be collected in self-reported questionnaire and graded using toxicity grading scale.
Measure: Local and systemic adverse events to BCG vaccination in healthcare workers Time: Measured over the 3 months following randomisationCoronavirus disease 2019 (COVID-19) was recognized as a pandemic on March 11, 2020 by the World Health Organization. The virus that causes COVID-19 (SARS-CoV-2) is easily transmitted through person to person and there is still no specific approach against the disease and mortality rate in severe cases is also significant. Therefore, finding effective treatment for the mortality of these patients is very important. In this study the investigators aim to determine the effect of Convalescent Plasma on COVID-19 patients Outcome through a Clinical Trial
Description: Measure of the number of deaths in a particular population, scaled to the size of that population, per unit of time.
Measure: Mortality changes in day 10 Time: 10 days after plasma transmissionDescription: Measure of the number of deaths in a particular population, scaled to the size of that population, per unit of time.
Measure: Mortality changes in day 30 Time: 30 days after plasma transmissionDescription: Measurement of CRP
Measure: Changes of C-reactive protein Time: Day 1Description: Measurement of CRP
Measure: Changes of C-reactive protein Time: Day 3Description: Measurement of CRP
Measure: Changes of C-reactive protein Time: Day 7Description: Measurement of IL-6
Measure: Changes of Interleukin 6 Time: Day 1Description: Measurement of IL-6
Measure: Changes of Interleukin 6 Time: Day 3Description: Measurement of IL-6
Measure: Changes of Interleukin 6 Time: Day 7Description: Measurement of TNF-α
Measure: Changes of tumor necrosis factor-α Time: Day 1Description: Measurement of TNF-α
Measure: Changes of tumor necrosis factor-α Time: Day 3Description: Measurement of TNF-α
Measure: Changes of tumor necrosis factor-α Time: Day 7Description: Partial pressure of arterial oxygen/Percentage of inspired oxygen
Measure: Changes of PaO2/FiO2 Ratio Time: Day 1Description: Partial pressure of arterial oxygen/Percentage of inspired oxygen
Measure: Changes of PaO2/FiO2 Ratio Time: Day 3Description: Partial pressure of arterial oxygen/Percentage of inspired oxygen
Measure: Changes of PaO2/FiO2 Ratio Time: Day 7Description: Computed tomography Scan and Chest X-Ray
Measure: Radiological findings Time: Within 2 hours after admissionDescription: Computed tomography Scan and Chest X-Ray
Measure: Radiological findings Time: Day 14Primary Objective: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe or critical COVID-19 Secondary Objectives: - Evaluate the 28-day survival rate - Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity - Evaluate changes in the National Early Warning Score 2 (NEWS2) - Evaluate the duration of predefined symptoms and signs (if applicable) - Evaluate the duration of supplemental oxygen dependency (if applicable) - Evaluate the incidence of new mechanical ventilation use during the study - Evaluate the duration of new mechanical ventilation use during the Study - Evaluate the proportion of patients requiring rescue medication during the 28-day period - Evaluate need for admission into intensive care unit (ICU) - Evaluate duration of hospitalization (days) - The secondary safety objectives of the study are to evaluate the safety of sarilumab through hospitalization (up to day 29 if patient is still hospitalized) compared to the control arm as assessed by incidence of: - Serious adverse events (SAEs) - Major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia - Grade ≥2 infusion related reactions - Grade ≥2 hypersensitivity reactions - Increase in alanine transaminase (ALT) ≥3X upper limit of normal (ULN) (for patients with normal baseline) or >3X ULN AND at least 2-fold increase from baseline value (for patients with abnormal baseline) - Major or opportunistic bacterial or fungal infections
Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Time to improvement of 2 points in clinical status assessment from baseline using the 7-point ordinal scale Time: Baseline to Day 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Proportion of patients with one point improvement from baseline in clinical status assessment at days 4, 7, 15, 21, 29 using the 7-point ordinal scale Time: Baseline to Days 4, 7, 15, 21, 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Mean change in the 7-point ordinal scale from baseline to Days 4, 7, 15, 21, and 29 (or until discharge) Time: Baseline to Days 4, 7, 15, 21, 29 (or until discharge)Description: Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.
Measure: Time to resolution of fever Time: Baseline to Day 29Description: Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is defined as SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever is sooner.
Measure: Time to resolution of fever and improvement in oxygenation Time: Baseline to Day 29Description: Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period.
Measure: Days with fever Time: Baseline to Day 29Description: The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Time to change in NEWS2 from baseline Time: Baseline to Day 29Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Time to NEWS2 of <2 and maintained for 24 hours Time: Baseline to Day 29Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Mean change from baseline to days 4, 7, 15, 21, and 29 in NEWS2 Time: Baseline to days 4, 7, 15, 21, and 29Description: SpO2/FiO2 of 50 or greater compared to the nadir for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
Measure: Time-to-improvement in oxygenation Time: Baseline to Day 29Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
Measure: Alive off supplemental oxygen at day 29 Time: Day 29Description: Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.
Measure: Days of hypoxemia Time: Baseline to Day 29Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
Measure: Days of supplemental oxygen use Time: Baseline to Day 29Description: For those not requiring these interventions at baseline.
Measure: The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula Time: Baseline to Day 60Description: For patients are not in ICU at baseline
Measure: The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available) Time: Baseline to Day 60The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Most cases are mild or asymptomatic. However, around 5% of all patients develop Acute Respiratory Distress Syndrome (ARDS), which is the leading mortality cause in these patients. Corticosteroids have been tested in deferent scenarios of ARDS, including viral pneumonia, and the early use of dexamethasone is safe and appears to reduce the duration of mechanical ventilation in ARDS patients. Nevertheless, no large, randomized, controlled trial was performed evaluating the role of corticosteroids in patients with ARDS due SARS-CoV2 virus. Therefore, the present study will evaluate the effectiveness of dexamethasone compared to control (no corticosteroids) in patients with moderate and severe ARDS due to SARS-CoV2 virus.
Description: Ventilator-free days, defined as alive and free from mechanical ventilation, at 28 days after randomization.
Measure: Ventilator-free days Time: 28 days after randomizationDescription: Evaluation of the clinical status of patients on the 15th day after randomization defined by the 6-point Ordinal Scale, this scale ranges from 1 (Not hospitalized) to 6 (Death) with higher scores meaning worse outcomes.
Measure: Evaluation of the clinical status Time: 15 days after randomizationDescription: All-cause mortality rates at 28 days after randomization.
Measure: All-cause mortality Time: 28 days after randomizationDescription: Number of days of mechanical ventilation from randomization to day 28.
Measure: Mechanical ventilation duration Time: 28 days after randomizationDescription: Sequential Organ Failure Assessment (SOFA) Score 48 hours, 72 hours and 7 days after randomization
Measure: Sequential Organ Failure Assessment (SOFA) Score Time: Score at 48 hours, 72 hours and 7 days after randomizationDescription: Intensive Care Unit free days, defined as alive and discharged from the intensive care unit, at 28 days after randomization.
Measure: Intensive Care Unit free days Time: 28 days after randomizationCOVID-19 may cause severe pneumonitis that require ventilatory support in some patients, the ICU mortality is as high as 62%. Hospitals do not have enough ICU beds to handle the demand and to date there is no effective cure. We explore a treatment administered in a randomized clinical trial that could prevent ICU admission and reduce mortality. The overall hypothesis to be evaluated is that HBO reduce mortality, increase hypoxia tolerance and prevent organ failure in patients with COVID19 pneumonitis by attenuating the inflammatory response.
Description: The proportion of subjects admitted to ICU from day 1 to day 30, based on at least one of the following criteria: i) Rapid progression over hours ii) Lack of improvement on high flow oxygen >40L/min or non invasive ventilation with fraction of inspired oxygen (FiO2) > 0.6 iii) Evolving Hypercapnia or increased work of breathing not responding to increased oxygen despite maximum standard of care available outside ICU iv) Hemodynamic instability or multi organ failure with maximum standard of care available outside ICU
Measure: ICU admission Time: Through study completion 30 daysDescription: Proportion of subjects with 30-day mortality, all cause Mortality, from day 1 to day 30.
Measure: 30-day mortality Time: Through study completion 30 daysDescription: Time-to-Intubation, i.e. cumulative days free of invasive mechanical ventilation, from day 1 to day 30
Measure: Time-to-intubation Time: Through study completion 30 daysDescription: Time-to-ICU, i.e. cumulative ICU free days, derived as the number of days from day 1 to ICU, where all ICU free subjects are censored at day 30.
Measure: Time-to-ICU Time: Through study completion 30 daysDescription: Mean change in inflammatory response from day 1 to day 30. White cell count + differentiation Procalcitonin C-Reactive protein Cytokines (IL-6) (if available at local laboratory) Ferritin D-Dimer LDH
Measure: Inflammatory response Time: Through study completion 30 daysDescription: Overall survival (Kaplan-Meier)
Measure: Overall survival Time: Through study completion 30 daysDescription: Hospital mortality of any cause, proportion of subjects, from day 1 to day 30.
Measure: Hospital mortality Time: Through study completion 30 daysDescription: Proportion of subjects with ICU mortality, Mortality of any cause in ICU, from day 1 to day 30.
Measure: ICU mortality Time: From ICU admission to study completion 30 daysDescription: Time-to-stop of intubation/invasive mechanical ventilation, from ICU admission to day 30.
Measure: Time in Invasive Ventilation Time: From ICU admission to study completion 30 daysDescription: Mean daily NEWS from day 1 to day 30.
Measure: NEWS Time: Through study completion 30 daysDescription: Mean change in PaO2/FiO2 (PFI), from day 1 to day 2, … to day 30.
Measure: PaO2/FiO2 (PFI) Time: Through study completion 30 daysDescription: Proportion of HBO treatments given vs planned. Proportion of subjects with HBO treatment administered within 24h after enrolment.
Measure: HBO Compliance Time: Day 1 to day 7Description: Time-to-discharge from hospital
Measure: Hospital discharge Time: Through study completion 30 daysDescription: Mean oxygen dose per day including HBO and cumulative pulmonary oxygen toxicity expressed as Units of oxygen pulmonary toxicity dose (UPTD) and Cumulative pulmonary toxicity dose (CPTD) from day 1 to day 30.
Measure: Oxygen dose Time: Through study completion 30 daysDescription: Median number of HBO treatments and dose of HBO given, from day 1 to day 7
Measure: HBO dose Time: Day 1 to day 7Description: Change in expression of Micro RNA in plasma from day 1 to day 30
Measure: Micro RNA Time: Through study completion 30 daysDescription: Change in gene expression and Micro RNA interactions in Peripheral Blood Mononuclear Cells (PBMC) (20 Subjects) from day 1 to day 30
Measure: Hypoxic response Time: Through study completion 30 daysDescription: Immunological response (20 subjects) from day 1 to day 30 in the following. Cytokines extended including (IL-1β, IL-2, IL-6, IL33 and TNFα) Lymphocyte profile Flowcytometry with identification of monocyte/lymphocyte subsets including but not limited to CD3+/CD4+/CD8+ and CD4+/CD8+ ratio FITMaN panel/Flow cytometry, Interleukins (IL-1β, IL-2, IL-6, IL33 and TNFα), T-reg cells (CD3+/CD4+/CD25+/CD127+) Monocyte proliferation markers, Ex vivo monocyte function
Measure: Immunological response Time: Through study completion 30 daysDescription: Mean change in routine biomarkers for organ dysfunction, from day 1to day 30.
Measure: Multi organ dysfunction Time: Through study completion 30 daysDescription: Viral load, review of records from day 1 to day 30.
Measure: Viral load Time: Through study completion 30 daysDescription: Number of secondary infections, review of records, number of events and patients from day 1 to day 30.
Measure: Secondary infections Time: Through study completion 30 daysDescription: Diagnosed PE needing treatment, review of records, number of events and patients from day 1 to day 30.
Measure: Pulmonary embolism Time: Through study completion 30 daysDescription: Changes on Pulmonary CT, review of records from day 1 to day 30.
Measure: Pulmonary CT Time: Through study completion 30 daysDescription: Changes on Chest X-ray, review of records from day 1 to day 30.
Measure: Chest X-ray Time: Through study completion 30 daysDescription: Changes in Lung ultrasound, review of records from day 1 to day 30.
Measure: Lung ultrasound Time: Through study completion 30 daysThe COntAGIouS trial (COvid-19 Advanced Genetic and Immunologic Sampling; an in-depth characterization of the dynamic host immune response to coronavirus SARS-CoV-2) proposes a transdisciplinary approach to identify host factors resulting in hyper-susceptibility to SARS-CoV-2 infection, which is urgently needed for directed medical interventions.
Description: Description of clinical, laboratory and radiological features of illness and complications.
Measure: Clinical Features Time: 6 monthsDescription: Evaluation of dynamic host immune response at systemic level (immune signalling molecules in plasma, peripheral blood mononuclear cell isolation for advanced immunophenotyping and transcriptomics). Real-time analysis using CyTOF will be performed as screening, in combination with in-depth immunophenotyping.
Measure: Immune host response at systemic level Time: 6 monthsDescription: Evaluation of dynamic host immune response at systemic level (immune signalling molecules in plasma, peripheral blood mononuclear cell isolation for advanced immunophenotyping and transcriptomics).
Measure: Immune host response at local level Time: 6 monthsDescription: Identification of host genetic variants that are associated with severity of disease.
Measure: Host genetic variation Time: 6 monthsDescription: Differences in baseline factors
Measure: Comparison severe and non-severe COVID-19 hospitalised patients Time: 6 monthsDescription: Differences in immune characteristics
Measure: Comparison severe and non-severe COVID-19 hospitalised patients Time: 6 monthsDescription: Correlation of findings with outcome, aiming to identify early biomarkers of severe disease and putative targets for immunomodulatory therapy
Measure: Correlation of findings with outcome Time: 6 monthsDescription: Correlation of immune profiling with microbiome analysis of patients
Measure: Correlation of immune profiling - microbiome Time: 6 monthsMinimal risk research study: 1. Comparing polyester nasal swabs and foam nasal swabs to detect SARS-CoV-2 virus; 2. Quantifying the development and trajectory of the disease through clinic visits and blood values.
Description: Measure the agreement between the detection of SARS-CoV-2 virus using a foam nasal swab tested directly after collection, a polyester nasal swab tested directly after testing, and a polyester nasal swab stored at room temperature for four days without saline or VTM before being tested.
Measure: Detection of SARS-CoV-2 virus Time: 42 daysDescription: Longitudinal blood samples from SARS-CoV-2 patients to gain a better understanding of the trajectory of COVID-19 and antibody development
Measure: Trajectory of COVID-19 and antibody development Time: 2 monthsThis study is a interventional study that present minimal risks and constraints to evaluate the presence of novel coronavirus (SARS-CoV-2) or antibodies among individuals living in households where there is a confirmed coronavirus case in order to provide useful information on the proportion of symptomatic forms and the extent of the virus transmission in a territory such as French Guiana.
Description: The extent of the virus transmission within households will be assessed by evaluating the rate of intra-household secondary transmission of the virus
Measure: Evaluation of the extent of the virus transmission within households Time: 2 yearsDescription: The characterization of the secondary cases will be assessed by evaluating the proportion of asymptomatic forms within the household
Measure: Characterization of the secondary cases Time: 2 yearsDescription: The characterization of the secondary cases will be assessed by characterizing the risk factors for coronavirus infection.
Measure: Characterization of the secondary cases Time: 2 yearsObjective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.
Description: Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.
Measure: COVID-19-free survival Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Measure: Incidence of confirmed SARS-CoV-2 detection Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.
Measure: Incidence of possible COVID-19 symptoms Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.
Measure: Incidence of all-cause study medicine discontinuation Time: up to 12 weeksDescription: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.
Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Measure: Incidence of Hospitalization for COVID-19 or death Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.
Measure: Incidence of study medication-related side effects Time: up to 12 weeksThis is a clinical study for the prevention of SARS-CoV-2 infection in adults exposed to the virus. This study will enroll up to 2000 asymptomatic men and women 18 to 80 years of age (inclusive) who are close contacts of persons with laboratory confirmed SARS-CoV-2 or clinically suspected COVID-19. Eligible participants will be enrolled and randomized to receive the intervention or placebo at the level of the household (all eligible participants in one household will receive the same intervention).
Description: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected daily for 14 days
Measure: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection Time: Day 1 through Day 14 after enrolmentDescription: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection from self-collected samples collected at study exit
Measure: Polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection Time: Day 28 after enrolmentDescription: Safety and tolerability of Hydroxychloroquine as SARS-CoV-2 PEP in adults
Measure: Rate of participant-reported adverse events Time: 28 days from start of Hydroxychloroquine therapyDescription: PCR-confirmed COVID-19 diagnosis
Measure: Incidence rates of COVID-19 through study completion Time: 28 days from enrolmentThe overall objective of the study is to determine the therapeutic effect and tolerance of Tocizilumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal transduction by binding sIL-6R and mIL-6R. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Tocilizumab administration to patients enrolled in the COVIMUNO-19 cohort. Tocilizumab will be administered to consenting adult patients hospitalized with CORVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Tocilizumab will receive standard of cares. Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.
Description: Group 1. Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measure: Survival without needs of ventilator utilization at day 14. Group 1 Time: 14 daysDescription: Group 1. Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale <=5 at day 4. Group 1. Time: 4 daysDescription: Group 2. Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14. Group 2. Time: 14 daysDescription: Group 2 Early end point : proportion of patients with a decrease of WHO score of at least 1 point at day 4. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale at day 4. Group 2. Time: 4 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
Measure: WHO progression scale Time: 7 and 14 daysDescription: Overall survival
Measure: Survival Time: 14, 28 and 90 daysDescription: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
Measure: respiratory acidosis at day 4 Time: 4 daysDescription: evolution of PaO2/FiO2 ratio
Measure: PaO2/FiO2 ratio Time: day 1 to day 14Description: time to oxygen supply independency
Measure: time to oxygen supply independency Time: 14 daysDescription: duration of hospitalization
Measure: duration of hospitalization Time: 90 daysDescription: time to negative viral excretion
Measure: time to negative viral excretion Time: 90 daysDescription: time to ICU discharge
Measure: time to ICU discharge Time: 90 daysDescription: time to hospital discharge
Measure: time to hospital discharge Time: 90 daysConvalescent plasma (CP) has been used in recent years as an empirical treatment strategy when there is no vaccine or treatment available for infectious diseases. In the latest viral epidemics, such as the Ebola outbreak in West Africa in 2014, the World Health Organization issued a document outlining a protocol for the use of whole blood or plasma collected from patients who have recovered from the Ebola virus disease by transfusion to empirically treat local infectious outbreaks.
Description: Copies of COVID-19 per ml
Measure: Change in Viral Load Time: Days 0, 4, 7, 14 and 28Description: Immunoglobulin M COVID-19 antibodies
Measure: Change in Immunoglobulin M COVID-19 antibodies Titers Time: Days 0, 4, 7, 14 and 28Description: Immunoglobulin G COVID-19 antibodies
Measure: Change in Immunoglobulin G COVID-19 antibodies Titers Time: Days 0, 4, 7, 14 and 28Description: Proportion of patients with Intensive Care Unit Admission requirement (days 7, 14 and 28)
Measure: Intensive Care Unit Admission Time: Days 7, 14 and 28Description: Days of Intensive Care Unit management (days 7, 14 and 28)
Measure: Length of Intensive Care Unit stay Time: Days 7, 14 and 28Description: Days of Hospitalization (days 7, 14 and 28)
Measure: Length of hospital stay (days) Time: Days 7, 14 and 28Description: Proportion of patients with mechanical ventilation (days 7, 14 and 28)
Measure: Requirement of mechanical ventilation Time: Days 7, 14 and 28Description: Days with mechanical ventilation (days 7, 14 and 28)
Measure: Duration (days) of mechanical ventilation Time: Days 7, 14 and 28Description: 1. Hospital discharge; 2. Hospitalization, not requiring supplemental oxygen; 3. Hospitalization, requiring supplemental oxygen (but not Noninvasive Ventilation/ HFNC); 4. Intensive care unit/hospitalization, requiring Noninvasive Ventilation/ HFNC therapy; 5. Intensive care unit, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 6. Death. (days 7, 14 and 28)
Measure: Clinical status assessed according to the World Health Organization guideline Time: Days 7, 14 and 28Description: Proportión of death patients at days 7, 14 and 28
Measure: Mortality Time: Days 7, 14 and 28Background: A novel Coronavirus (SARS-CoV-2) described in late 2019 in Wuhan, China, has led to a pandemic and to a specific coronavirus-related disease (COVID-19), which is mainly characterized by a respiratory involvement. While researching for a vaccine has been started, effective therapeutic solutions are urgently needed to face this threaten. The renin-angiotensin system (RAS) has a relevant role in COVID-19, as the virus will enter host 's cells via the angiotensin-converting enzyme 2 (ACE2); RAS disequilibrium might also play a key role in the modulation of the inflammatory response that characterizes the lung involvement. Angiotensin-(1-7) is a peptide that is downregulated in COVID-19 patient and it may potentially improve respiratory function in this setting. Methods/Design: The Investigators describe herein the methodology of a randomized, controlled, adaptive Phase II/Phase III trial to test the safety, efficacy and clinical impact of the infusion of angiotensin-(1-7) in COVID-19 patients with respiratory failure requiring mechanical ventilation. A first phase of the study, including a limited number of patients (n=20), will serve to confirm the safety of the study drug, by observing the number of the severe adverse events. In a second phase, the enrollment will continue to investigate the primary endpoint of the study (i.e. number of days where the patient is alive and not on mechanical ventilation up to day 28) to evaluate the efficacy and the clinical impact of this drug. Secondary outcomes will include the hospital length of stay, ICU length of stay, ICU and hospital mortality, time to weaning from mechanical ventilation, reintubation rate, secondary infections, needs for vasopressors, PaO2/FiO2 changes, incidence of deep vein thrombosis, changes in inflammatory markers, angiotensins plasmatic levels and changes in radiological findings. The estimated sample size to demonstrate a reduction in the primary outcome from a median of 14 to 11 days is 56 patients, 60 including a dropout rate of 3% (i.e. 30 per group), but a preplanned recalculation of the study sample size is previewed after the enrollment of 30 patients. Expected outcomes/Discussion: This controlled trial will assess the efficacy, safety and clinical impact of the Angiotensin-(1-7) infusion in a cohort of COVID-19 patients requiring mechanical ventilation. The results of this trial may provide useful information for the management of this disease.
Description: composite outcome of mortality and necessity of mechanical ventilation
Measure: ventilator free days Time: 28 daysDescription: number of days free from intensive care unit
Measure: ICU free days Time: trough study completion, on average 40 daysDescription: Hospital length of stay
Measure: Hospital length of stay Time: through study completion, on average 60 daysDescription: Time to wean from mechanical ventilation
Measure: Time to wean from mechanical ventilation Time: through study completion, on average 14 daysDescription: PaO2/FiO2 changes during drug administration
Measure: PaO2/FiO2 changes during drug administration Time: 48 hoursDescription: US confirmed deep vein thrombosis
Measure: Deep vein thrombosis incidence Time: through study completion, on average 30 daysDescription: including IL-1, IL-2, IL-6, IL-7, IL-8, IL-10, TNF-alpha, interferon gamma
Measure: Changes in inflammatory markers Time: at randomization, 48 hours after randomization and 72 hours after randomizationDescription: Ang II and Ang-(1-7) plasmatic levels
Measure: RAS effectors levels Time: at randomization, 48 hours after randomization and 72 hours after randomizationDescription: Chest x-ray or CT scan changes
Measure: Radiological findings Time: through study completion, on average 30 daysDescription: phase 2b = principal safety outcome; phase 3 = secondary outcome
Measure: Rate of serious adverse events Time: study drug administration/day 28 or ICU discharge or deathConvalescent plasma (CP) has been used in recent years as an empirical treatment strategy when there is no vaccine or treatment available for infectious diseases. In the latest viral epidemics, such as the Ebola outbreak in West Africa in 2014, the World Health Organization issued a document outlining a protocol for the use of whole blood or plasma collected from patients who have recovered from the Ebola virus disease by transfusion to empirically treat local infectious outbreaks
Description: Copies of COVID-19 per ml
Measure: Change in Viral Load Time: Days 0, 4, 7, 14 and 28Description: Immunoglobulin M COVID-19 antibodies
Measure: Change in Immunoglobulin M COVID-19 Titers Time: Days 0, 4, 7, 14 and 28Description: Immunoglobulin G COVID-19 antibodies
Measure: Change in Immunoglobulin G COVID-19 Titers Time: Days 0, 4, 7, 14 and 28Description: Proportion of patients with Intensive Care Unit Admission requirement (days 7, 14 and 28)
Measure: Intensive Care Unit Admission Time: Days 7, 14 and 28Description: Days of Intensive Care Unit management (days 7, 14 and 28)
Measure: Length of Intensive Care Unit stay Time: Days 7, 14 and 28Description: Days of Hospitalization (days 7, 14 and 28)
Measure: Length of hospital stay (days) Time: Days 7, 14 and 28Description: Proportion of patients with mechanical ventilation (days 7, 14 and 28)
Measure: Requirement of mechanical ventilation Time: Days 7, 14 and 28Description: Days with mechanical ventilation (days 7, 14 and 28)
Measure: Duration (days) of mechanical ventilation Time: Days 7, 14 and 28Description: 1. Hospital discharge; 2. Hospitalization, not requiring supplemental oxygen; 3. Hospitalization, requiring supplemental oxygen (but not Noninvasive Ventilation/ HFNC); 4. Intensive care unit/hospitalization, requiring Noninvasive Ventilation/ HFNC therapy; 5. Intensive care unit, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 6. Death. (days 7, 14 and 28)
Measure: Clinical status assessed according to the World Health Organization guideline Time: Days 7, 14 and 28Description: Proportion of death patients at days 7, 14 and 28
Measure: Mortality Time: Days 7, 14 and 28ORCHID is a multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.
Description: We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: Death Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)
Measure: COVID Ordinal Outcomes Scale on Day 15 Time: assessed on study day 15Description: Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 15 Time: assessed on study day 15Description: Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 29 Time: assessed on study day 29Description: We will determine the COVID Ordinal Scale for all patients on study day 3
Measure: COVID Ordinal Outcomes Scale on Study Day 3 Time: assessed on study day 3Description: We will determine the COVID Ordinal Scale on study day 8
Measure: COVID Ordinal Outcomes Scale on Study Day 8 Time: assessed on study day 8Description: We will determine the COVID Ordinal Scale on study day 29
Measure: COVID Ordinal Outcomes Scale on Study Day 29 Time: assessed on study day 29Description: We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28
Measure: Number of patients dead or with receipt of ECMO between enrollment and Day 28 Time: Enrollment to Day 28Description: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days.
Measure: Oxygen-free days through Day 28 Time: 28 days after randomizationDescription: Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.
Measure: Ventilator-free days through Day 28 Time: 28 days after randomizationDescription: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days.
Measure: Vasopressor-free days through Day 28 Time: 28 days after randomizationDescription: The number of days spent out of the ICU to day 28.
Measure: ICU-free days to Day 28 Time: 28 days after randomizationDescription: Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.
Measure: Hospital-free days to Day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience seizure between randomization and day 28
Measure: Number of patients with seizures to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28
Measure: Number of patients with atrial or ventricular arrhythmia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience cardiac arrest between randomization and day 28
Measure: Number of patients with cardiac arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28
Measure: Number of patients with elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute pancreatitis between randomization and day 28
Measure: Number of patients with acute pancreatitis arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute kidney injury between randomization and day 28
Measure: Number of patients with acute kidney injury to day28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience renal replacement therapy between randomization and day 28
Measure: Number of patients with receipt of renal replacement therapy to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28
Measure: Number of patients with symptomatic hypoglycemia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience neutropenia, lymphopenia, anemia, or thrombocytopenia between randomization and day 28
Measure: Number of patients with neutropenia, lymphopenia, anemia, or thrombocytopenia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28
Measure: Number of patients with severe dermatologic reaction to day 28 Time: 28 days after randomizationWhereas the pandemic due do Covid-19 continues to spread, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Severe Acute Respiratory Distress Syndrome in 30% of patients with a 30%-60% mortality rate for those requiring hospitalization in an intensive care unit. The main physio-pathological hallmark is an acute pulmonary inflammation. Currently, there is no treatment. Mesenchymal stem cells (MSC) feature several attractive characteristics: ease of procurement, high proliferation potential, capacity to home to inflammatory sites, anti-inflammatory, anti-fibrotic and immunomodulatory properties. If all MSC share several characteristics regardless of the tissue source, the highest productions of bioactive molecules and the strongest immunomodulatory properties are yielded by those from the Wharton's jelly of the umbilical cord. An additional advantage is that they can be scaled-up to generate banks of cryofrozen and thus readily available products. These cells have already been tested in several clinical trials with an excellent safety record. The objective of this project is to treat intubated-ventilated patients presenting with a SARS-CoV2-related Acute Respiratory Distress Syndrome (ARDS) of less than 96 hours by three intravenous infusions of umbilical cord Wharton's jelly-derived mesenchymal stromal cells (UC-MSC) one every other day (duration of the treatment: one week). The primary endpoint is the PaO2/FiO2 ratio at day 7. The evolution of several inflammatory markers, T regulatory lymphocytes and donor-specific antibodies will also be monitored. The trial will include 40 patients, of whom 20 will be cell-treated while the remaining 20 patients will be injected with a placebo solution in addition to the standard of care. Given the pathophysiology of SARS-CoV2, it is thus sound to hypothesize that the intravenous administration of UC-MSC during the initial phase of ARDS could control inflammation, accelerate its recovery with improved oxygenation, reduced mechanical ventilation and ventilation weaning time and therefore reduced length of stay in intensive care. The feasibility of the project is supported by the expertise of the Meary Cell and Gene Therapy Center, which is approved for the production of Advanced Therapy Medicinal Products and has already successfully prepared the first batches of cells, as well as by the involvement of a cardiac surgery team which will leverage its experience with stem cells for the treatment of heart failure to make it relevant to the Stroma-Cov-2 project.
Patients with documented COVID-19 infection will be randomized 1:1 to receive Piclidenoson 2 mg Q12H orally with standard care (intervention arm) or standard care alone (control arm).
Description: The duration of viral shedding in days since initial diagnosis, as determined by RT-PCR to COVID-19
Measure: Duration of viral shedding in days Time: 28 daysDescription: TTCR is defined as the time (in hours) from initiation of trial treatment until normalization of fever, respiratory rate, and oxygen saturation, and alleviation of cough, sustained for at least 72 hours
Measure: Time to clinical recovery (TTCR) in days Time: 28 daysDescription: Proportion of patients experiencing AEs
Measure: Treatment-emergent adverse events (AEs) Time: 28 daysDescription: Proportion of patients requiring non-invasive or mechanical ventilation
Measure: Requirement for non-invasive or mechanical ventilation Time: 28 daysDescription: Duration of hospital stay
Measure: Length of hospital stay in days Time: 28 daysDescription: Ratio of arterial oxygen partial pressure to fractional inspired oxygen
Measure: Estimated PaO2/FiO2 ratio on day of discharge Time: 28 daysDescription: Proportion of patients who die
Measure: All-cause mortality Time: 28 daysDescription: Proportion of patients reaching undetectable COVID-19 virus levels in respiratory secretions at selected timepoints
Measure: Patients reaching undetectable COVID-19 virus levels in respiratory secretions Time: 28 daysDescription: Duration of symptoms and signs of respiratory infection associated with COVID-19
Measure: Duration of symptoms and signs of respiratory infection in days Time: 28 daysDescription: Proportion of patients who need for supportive respiratory management
Measure: Need for supportive respiratory management Time: 28 daysDescription: COVID-19 viral load in respiratory secretions using a semi-quantitative method
Measure: Viral load Time: 28 daysDescription: Proportion of patients experiencing AEs
Measure: Treatment-emergent serious AEs (SAEs) Time: 28 daysDescription: Rate of AEs leading to early discontinuation of trial treatment
Measure: AEs leading to withdrawal Time: 28 daysDescription: Proportion of patients experiencing treatment-emergent changes in clinical laboratory
Measure: Treatment-emergent abnormalities in clinical laboratory parameters Time: 28 daysPrimary Objective: To assess the effect of hydroxychloroquine versus placebo on nasopharyngeal SARS-CoV-2 viral load in outpatient adults with COVID-19 Secondary Objectives: - To assess the effect of hydroxychloroquine versus placebo on clinical signs and symptoms and progression of disease in outpatient adults with COVID-19 - To assess the safety and tolerability of hydroxychloroquine in outpatient adults with COVID-19
Description: Viral load assessed by PCR from a nasopharyngeal swab
Measure: Change from baseline to Day 3 in nasopharyngeal SARS-CoV-2 viral load (if quantitative PCR is available) Time: Baseline to Day 3Description: Viral load assessed by PCR from a nasopharyngeal swab - 2. Viral load assessed by PCR from a nasopharyngeal swab
Measure: Number of participants by PCR result status (positive or negative) (if quantitative PCR is not available) Time: Baseline to Day 3Description: Viral load assessed by PCR from a nasopharyngeal swab
Measure: Change from baseline to Day 5 in nasopharyngeal SARS-CoV-2 viral load Time: Baseline to Day 5Description: Viral load assessed by PCR from a nasopharyngeal swab
Measure: Number of participants by PCR result status (positive or negative) Time: Baseline to end of study (Day14)Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe)
Measure: Number of participants with COVID-19 symptoms by severity Time: Baseline to end of study (Day14)Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe). Resolution of a symptom is defined as when a symptom previously scored ≥ 1 on the scale is scored as 0
Measure: Time to resolution of COVID-19 Symptoms Time: Baseline to end of study (Day14)Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C
Measure: Time to resolution of fever Time: Baseline to end of study (Day14)Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C
Measure: Percentage of participants with resolution of fever Time: Baseline to end of study (Day14)In December 2019, a new virus emerged in Wuhan, China rapidly becoming a pandemic with registered cases above 800,000 around the world. The virus is now known as SARS-CoV2 calling its disease coronavirus-19 or COVID-19. The mortality of the virus has been reported around 2-10% and its causes because of the proinflammatory immune response generated on the host. The cytokines involved in the immune response to COVID-19 are IL-1, IL-2, IL4, IL-6, IL-10, IL-12, IL-13, IL-17, GCSF, MCSF, IP-10, MCP-1, MIP-1α, HGF, IFN-γ y TNF-α. Ruxolitinib is an inhibitor of JAK 1/2 which is responsable for multiple cellular signals including the proinflammatory IL-6. Ruxolitinib works as and immunomodulator decreasing the cytotoxic T lymphocytes and increasing the Treg cells. This study is intended to stop the disregulated immune response caused by COVID-19 that generates the pneumonia and subsequent severe acute respiratory syndrome.
Description: Presence of recovery of pneumonia characterized by cease of respiratory symptoms
Measure: Recovery of Pneumonia Time: 14 daysDescription: Increment or decrease in mg/ml of C-reactive protein
Measure: Response of C-reactive protein Time: 14 daysDescription: Increment or decrease in ng/ml of ferritin
Measure: Response of Ferritin Time: 14 daysDescription: Increment or decrease in mg/ml of D-dimer
Measure: Response of D-dimer Time: 14 daysDescription: Requirement of Intensive Care Unit on the patients under treatment
Measure: Rate of ICU admission Time: 14 daysDescription: Requirement of mechanical ventilation on the patients under treatment
Measure: Rate of mechanical ventilation Time: 14 daysDescription: Time since the diagnosis to the last follow up (recovery or death)
Measure: Overall Survival Time: 1 monthDescription: Rate of adverse events associated with ruxolitinib
Measure: Toxicity Rate Time: 1 monthThis is a Phase II interventional study will test the efficacy of quintuple therapy (Hydroxychloroquine, Azithromycin, Vitamin C, Vitamin D, and Zinc) in the treatment of patients with COVID-19 infection).
Description: Number of days from COVID-19 diagnosis to recovery via RT-PCR
Measure: The rate of recovery of mild or moderate COVID-19 in patients using Quintuple Therapy Time: 12 weeksDescription: Reduction and/or progression of symptomatic days, reduction of symptom severity
Measure: Reduction or Progression of Symptomatic Days Time: 12 weeksDescription: Assess the symptom response to study therapy as measured by the survey in the EDC
Measure: Assess the safety of Quintuple Therapy Time: 12 weeksDescription: Pulse from baseline to 12 weeks
Measure: Assess the safety of Quintuple Therapy via pulse Time: 12 weeksDescription: Oxygen saturation from baseline to 12 weeks
Measure: Assess the safety of Quintuple Therapy via oxygen saturation Time: 12 weeksDescription: EKG response from baseline to 12 weeks
Measure: Assess the safety of Quintuple Therapy via EKG Time: 12 weeksDescription: Assess Adverse Events and Serious Adverse Events due to Quintuple Therapy
Measure: Assess Tolerability of Quintuple Therapy Time: 12 weeksThe study aims to evaluate the reduction in severity and progression of lung injury with three doses of lipid ibuprofen in patients with SARS-CoV-2 infections.
Description: Worsening respiratory failure; defined using severity of hypoxaemia using [PaO2/FiO2 ratio OR SpO2/FiO2 ratio]
Measure: Disease progression Time: 14 daysDescription: Time to mechanical ventilation (or need of)
Measure: Time to mechanical ventilation Time: 14 daysHealthcare workers are particularly at risk of SARS-CoV-2. This study aims to assess the efficacy of a daily single dose of tenofovir disoproxil fumarate (TDF) (245 mg)/ Emtricitabine (FTC) (200 mg), a daily single dose of hydroxychloroquine (HC) (200 mg), a daily single dose of TDF (245 mg)/FTC (200 mg) plus HC (200 mg) versus placebo, during 12 weeks in: (1) reducing the incidence of symptomatic disease and (2) reducing clinical severity COVID-19 among hospital healthcare workers aged 18 to 70 years in public and private hospitals in Spain.
Description: assessed by: No symptoms Mild symptoms: general malaise, fever, cough, myalgia, asthenia. Moderate symptoms: mild symptoms plus shortness of breath, Severe symptoms: mild symptoms plus respiratory insufficiency that requires admission in intensive care unit and mechanical ventilation
Measure: Severity of disease in confirmed infected participants of SARS-CoV-2 (COVID-19) Time: 12 weeksThis study will assess the efficacy of hydroxychloroquine in reducing the severity of symptoms in patients with COVID-19
Description: This outcome will be assessed by comparing the percentages of enrolled patients that are hospitalized in the treatment and control arms.
Measure: Total Hospitalization Time: 14 daysDescription: This outcome will be assessed by comparing the percentages of enrolled patients that have received mechanical ventilation in the treatment and control arms.
Measure: Total Mechanical Ventilation Time: 14 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 2 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 5 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 10 daysDescription: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.
Measure: Fever intensity measure Time: 14 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 2 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 5 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 10 daysDescription: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.
Measure: Shortness of breath measure Time: 14 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 2 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 5 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 10 daysDescription: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in daytime cough measure Time: 14 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 2 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 5 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 10 daysDescription: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.
Measure: Changes in nighttime cough measure Time: 14 daysDescription: Number of enrolled patients who have died within the specified time frame
Measure: Total mortality Time: 28 daysThis is a Phase II interventional study testing whether treatment with hydroxychloroquine, Vitamin C, Vitamin D, and Zinc can prevent symptoms of COVID-19
Description: Any symptoms of COVID-19 will be recorded in a daily diary. Symptoms (including fever measured in degrees Fahrenheit, dry cough, productive cough, difficulty speaking, wheezing, dry mouth, headache, chest tightness, difficulty with exertion, shortness of breath, sore throat, malaise, and diarrhea) will be rated as not present, mild, moderate, or severe.
Measure: Prevention of COVID-19 symptoms as recorded in a daily diary Time: 24 weeksDescription: To assess the presence or absence of side effects (graded 1-5), and whether they are tolerable (grade 1-2). AE and SAE will be recorded.
Measure: Safety as determined by presence or absence of Adverse Events and Serious Adverse Events Time: 24 weeksThe objective of this study is to evaluate the clinical characteristics and outcomes of critically ill patients with COVID-19 admitted to the intensive care unit. A Multicenter Observational Study.
Description: Mortality 30 days following hospital admission
Measure: Hospital mortality Time: 30 daysDescription: The number of calendar days from the day of admission (counted as 1 day) to day of intensive care unit discharge
Measure: Length of stay in the intensive care unit Time: Through study completion, an average of 30 daysThis is an open-label trial to evaluate the safety, tolerability and immunological profile of INO-4800 administered by intradermal (ID) injection followed by electroporation (EP) using CELLECTRA® 2000 device in healthy adult volunteers.
We hypothesized: During the COVID-19 pandemic, the sleep quality of pregnant women decreases. During the COVID-19 epidemic, the stress level of pregnant women increases. During the COVID-19 epidemic, the level of physical activity of pregnant women decreases. Aims: The aim of the study is to determine the sleep quality, stress level and physical activity level of pregnant women who maintain the home quarantine during the COVID-19 pandemic.
Description: This measure assesses the types of intensity of physical activity and sitting time that people do as part of their daily lives are considered to estimate total physical activity in MET-min/week and time spent sitting. Walking = 3.3 METs Moderate Intensity = 4.0 METs Vigorous Intensity = 8.0 METs Total MET-minutes/week = Walk (METs*min*days) + Mod (METs*min*days) + Vig (METs*min*days) 1. Low: • No activity is reported OR • Some activity is reported but not enough to meet Categories 2 or 3. 2. Moderate: • 3 or more days of vigorous activity of at least 20 minutes per day OR • 5 or more days of moderate-intensity activity and/or walking of at least 30 minutes per day OR • 5 or more days of any combination of walking, moderate-intensity or vigorous intensity activities achieving a minimum of at least 600 MET-minutes/week. 3. High: • Vigorous-intensity activity on at least 3 days and accumulating at least 1500 MET-minutes/week
Measure: International Physical Activity Questionnaire Time: Baseline of the studyDescription: The Pittsburgh Sleep Quality Index (PSQI) is an effective instrument used to measure the quality and patterns of sleep. It differentiates "poor" from "good" sleep by measuring seven domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction over the last month.The client self rates each of these seven areas of sleep. Scoring of the answers is based on a 0 to 3 scale, whereby 3 reflects the negative extreme on the Likert Scale. A global sum of "5"or greater indicates a "poor" sleeper.
Measure: Pittsburgh Sleep Quality Index Time: Baseline of the studyDescription: The Perceived Stress Scale (PSS) is a 14-item self-report measure designed to assess "the degree to which situations in one's life are appraised as stressful. Each item is rated on a 5-point scale (0 = Never, 1 = Almost Never, 2 = Sometimes, 3 = Fairly Often, 4 = Very Often) and summed to create a total score. PSS-14 has strong internal consistency (α = .84 to .86) and good test-retest reliability (r = .85 over a 2-day period, r = .55 over a 6-week period.
Measure: Perceived Stress Scale Time: Baseline of the studyDescription: The Numeric Rating Scale (NRS) is the simplest and most commonly used numeric scale rates the pain from 0 (no pain) to 10 (worst pain).
Measure: Numerical Pain Rating Scale Time: Baseline of the studySince the last 3 months the world copes with the novel coronavirus disease : Covid-19 emerged in China in the end of 2019. WHO declared the pandemic situation as a Public Health Emergency around the world on January 2020. Firsts studies emphasized on higher risk to older adults to experience serious health consequences : hospitalizations and mortality, due to multimorbidity and multimedication. Nursing home resident are particulary frailer and vulnerable.
This is a multi-center, randomized, controlled, phase II clinical efficacy study evaluating a novel Nitric Oxide Releasing Solution (NORS) treatment for the prevention and treatment of COVID-19 in healthcare workers at risk of infection. Participants will be enrolled into one of two components of this study. Based on initial swabs/symptoms, volunteers who are COVID-19 negative will be enrolled in the Prevention study and randomized to receive standard institutional precautions or standard institutional precautions + NORS. Those who are COVID-19 positive will be enrolled in the open-label Treatment Sub-Study.
Description: Measure the proportion of subjects with either swab positive COVID-19 or presentation of clinical symptoms as measured by fatigue with either fever >37.2 (oral)and/or a persistent cough.
Measure: Prevention Study: Measure the effect of NORS on the prevention of COVID-19 infection among health care professionals at risk of exposure to COVID-19 Time: 14 daysDescription: Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Measure: Treatment Sub Study: Measure the efficacy of NORS at reducing the progression of COVID- 19 Time: 21 daysDescription: Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Measure: Prevention Study: Measure the effect of NORS on the prevention of progression of COVID- 19 Time: 21 daysDescription: Measure the tolerability of the NORS treatments as determined by number of adverse events, pain, discomfort or discontinuations of treatment.
Measure: Prevention Study: Measure the tolerability of NORS treatments Time: 21 daysDescription: Measure the median number of days to negative conversion of SARS-CoV-2 RT-PCR from a nasopharyngeal swabs.
Measure: Treatment Sub Study: Measure the virucidal effect of NORS Treatments Time: 21 daysDescription: Determine the time to clinical recovery in participants with COVID-19 by measuring the median number of days from enrollment to discharge (if admitted), or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air).
Measure: Treatment Sub Study: Determine effect of NORS on the speed of clinical recovery Time: 21 daysDescription: Measure the reduction clinical symptoms in participants with COVID- 19 by the magnitude of the change in Modified Jackson Cold Score Diary Score (5-unit change is a substantial clinical benefit).
Measure: Treatment Sub Study: Determine the reduction in clinical symptoms Time: 21 daysDescription: Measure the proportion of participants that have a positive sero-conversion for SARS-CoV-2
Measure: Treatment & Sub Study: Determine positive sero-conversion for SARS-CoV-2 Time: 21 daysCOVID-19 pandemic has developed worldwide in less than 4 months. While most patients have a mild or uncomplicated disease (80%), approximately 15% need hospital care and 5% intensive care. Severe cases are characterized by pulmonary involvement which may progress to acute respiratory distress syndrome (ARDS). Early identification of patients who are likely to get worse is therefore a major issue. While, chest X-ray has poor diagnostic performances, pulmonary computed tomography (CT scan) seems very sensitive (97%) and quite specific of COVID-19. Sub-pleural bilateral ground-glass pattern can precede the positivity of RT-PCR for SARS-CoV-2. CT scan is now considered as the best imaging test to assess COVID-19 patients and is recommended as first-line diagnosis tool by the French Society of Radiology (SFR). However, performing CT scan in all or many patients with suspected COVID-19 may result in radiology department overload, especially, taking into account bio-cleaning between patients. Moreover, CT scan may lead to adverse effects including induced cancer due to the cumulative diagnostic irradiation. Chest ultrasonography may be an alternative to CT scan. It is a simple, non-invasive, non-irradiating, inexpensive and available at the point of care (POCUS). Most of emergency physicians and many other specialists (pneumologists, infectious disease or intensive care physicians) are trained to perform chest POCUS and use it in their everyday practice. Multiple studies have demonstrated its superiority to chest X-ray for the detection of pneumonia. In ARDS, a scoring has been developed and has shown good correlation with mortality. POCUS is very effective in detecting peripheral patterns and seems appropriate to explore COVID-19 patients. Previous studies suggest its interest in SARSCov2 infections for initial patient assessment and identification of lung damage. However, its performances have never been scientifically evaluated to date. Our main hypothesis is that point of care lung ultrasonography performed during the initial examination may identify high-risk COVID-19 patients.
Description: To assess, in patients with confirmed or probable SARS-CoV-2 infection, chest ultrasonography capacity, using the POCUS score for ARDS, to identify patients with unfavourable outcome at D14. Unfavourable outcome is defined by intubation with mechanical ventilation requirement or death (Stage ≥ 6 on "Ordinal Scale for Clinical Improvement" of the World Health Organization) within 14 days of inclusion. We will determine the 95% confidence interval of the AUC of the ROC curve and consider POCUS capacity as clinically relevant if the lower limit of the 95% confidence interval is at least 0.7.
Measure: Risk of unfavourable outcome at D14 Time: 14 daysDescription: To evaluate, in patients with a confirmed or probable SARS-CoV-2 infection, whether POCUS score performances vary as a function of time, between D1 and D14, and, if so, until which time horizon its performances are clinically relevant. In this purpose, we will determine the time period for which the lower limit of the 95% confidence interval of the AUC of the POCUS score ROC curve is at least 0.7.
Measure: Risk of unfavourable outcome over time Time: 14 daysDescription: To identify the threshold values of POCUS score to perform risk-stratification in three groups of patients: low-risk patients, intermediate-risk patients, high-risk patients. In this purpose, we will determine two threshold values on the inflection points of the ROC curve: maximizing the specificity for a sensitivity of at least 95%, maximizing the sensitivity for a specificity of at least 95%.
Measure: Risk-stratification threshold values Time: 14 daysDescription: To study the impact of adding the result of POCUS evaluation to several risk-stratification clinical rules for pulmonary infection or sepsis: qSOFA, CRB 65 and CURB 65 In this purpose, we will attribute 0, 1 or 2 points to POCUS score according to the predefined threshold values and will assess : sensitivities of qSOFA with and without addition of POCUS score result, specificities of qSOFA with and without addition of POCUS score result; sensitivities of CRB 65 with and without addition of POCUS score result, specificities of CRB 65 with and without addition of POCUS score result; sensitivities of CRB 65 with and without addition of POCUS score result, specificities of CRB 65 with and without addition of POCUS score result.
Measure: Adding value of POCUS score to previous risk-stratification clinical rules Time: 14 daysDescription: To assess, the capacity of POCUS score at D0 to predict patient clinical status at D14 In this purpose, we will determine the correlation coefficient between the POCUS score at D0 and the clinical status of patients at day 14 according to the WHO Ordinal Scale for Clinical Improvement for COVID-19 patients.
Measure: POCUS score and patient clinical status at D14 Time: 14 daysDescription: To study the correlation between POCUS and CT scan assessment of lung damage. In this purpose, we will determine the intra-class correlation coefficient between POCUS assessment according to the number of affected areas among 12 and CT scan assessment according to the quantification proposed by the French Society of Radiology: 0 - normal; 1 - minor (< 10%), 2 - moderate (10-25%), 3 - important (25-50%), 4 - severe (50-75%), 5 - critical (> 75%)
Measure: POCUS and CT scan correlation Time: 14 daysDescription: To compare the diagnostic performances of POCUS with that of chest computed tomography to identify patients with unfavourable outcome. In this purpose, we will compare the AUC of the ROC curves of POCUS score and CT scan quantification of lung damage to identify patients with unfavourable outcome (intubation and mechanical ventilation requirement or death)
Measure: POCUS versus CT scan risk-stratification performances Time: 14 daysDescription: To evaluate, in the subgroup of hospitalized patients having a second chest ultrasonography at Day 5 +/- 3 of inclusion, the performances of the evolution of the POCUS score between the first and the second assessment to identify patients with unfavourable outcome. In this purpose, we will calculate the delta between the first and second POCUS score and determine the AUC of the ROC curve and its 95% confidence interval.
Measure: POCUS score evolution performances Time: 14 daysCOVID-19 pandemic has developed worldwide in less than 4 months. The clinical presentations are variable widely, ranging from simple rhinitis to major lung damage that can lead to death. In many countries involved in the ongoing health disaster due to SARS-CoV-2 infection, hospital are overloaded. In this context, the decision to hospitalize or to manage COVID-19 patients at home is crucial and defining reliable and consensual criteria is a major issue. HOME-CoV study is a multicentre quasi-experimental interventional study, before and after implementation of a help-decision making rule (HOME-CoV rule), developed via the Delphi method. Our main hypothesis is that a strategy based on the consensual HOME-CoV rule compared to current practice is at least as safe as regards the 7-day-rate of adverse events (safety criterion) and more effective as regards the rate of patients eventually managed as outpatients (efficacy criterion).
Description: Adverse outcomes include intubation with mechanical ventilation requirement and death (Stage ≥ 6 on "Ordinal Scale for Clinical Improvement" of the World Health Organization) within 7 days after inclusion.
Measure: the composite rate of adverse outcomes Time: day 7Description: The rate of patients hospitalized after admission to the emergency room including patients discharged home more than 24 hours after admission. It will be analyzed in a hierarchical approach, only if first primary objective is positive i.e. non-inferiority of HOME-CoV strategy versus current practice on the rate of adverse outcomes.
Measure: The rate of hospitalization Time: 24 hoursWe seek to derive and validate a clinically useful risk score for patients with Coronavirus Disease 2019 to aide clinicians in the safe discharge of patients.
Description: Patient with COVID-19 who does not require supplemental oxygen, does not require intensive care unit-level care, and does not die.
Measure: Suitable for discharge Time: Duration of participation in cohort, expected to be between 1 day and 20 days.Our aim is to conduct one trial of personalized immunotherapy in patients with SARS-CoV-2 (COVID-19) associated with organ dysfunction and with laboratory findings of macrophage activation syndrome or immune dysregulation. These patients will be selected by the use of a panel of biomarkers and laboratory findings and they will be allocated to immunotherapy treatment according to their needs.
Description: At least 25% decrease between baseline sequential organ failure assessment SOFA score and measured sequential organ failure assessment SOFA score at Study Day 8
Measure: Change of baseline total sequential organ failure assessment (SOFA) score Time: Visit study day 8Description: Resolution of all criteria of lower respiratory tract involvemed that led to study inclusion (except findings from imaging studies) at Study Day 8
Measure: Improvement of lung involvement measurements Time: Visit study day 8Description: At least 50% increase of pO2/FiO2 ratio between baseline and study visit Day 8
Measure: Increase of pO2/FiO2 ratio Time: Visit Study Day 8Description: Change of total sequential organ failure assessment (SOFA) score between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Comparison of change of baseline total sequential organ failure assessment (SOFA) score in enrolled subjects towards historical comparators Time: Screening, Day 8Description: Change of lung involvement measurements between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of change of lung involvement measurements in enrolled subjects towards historical comparators Time: Screening, Day 8Description: Comparison of increase in pO2/FiO2 ratio towards historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of pO2/FiO2 ratio in enrolled subjects towards historical comparators Time: Screening, Day 8Description: Change of Sequential organ failure assessment (SOFA) score on day 28 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of sequential organ failure assessment (SOFA) score Time: Day 28Description: Mortality on day 28
Measure: Rate of Mortality Time: Day 28Description: Mortality on day 90
Measure: Rate of Mortality Time: Day 90Description: Cytokine stimulation from peripheral blood mononuclear cells will be compared between days 0 and 4
Measure: Cytokine stimulation Time: Screening, Day 4Description: Gene expression of peripheral blood mononuclear cells will be compared between days 0 and 4
Measure: Gene expression Time: Screening, Day 4Description: Change of serum/plasma proteins between days 0 and 4
Measure: Serum/plasma proteins Time: Screening, Day 4Description: Classification of immune function of screened patients who are not enrolled in study drug since they are not characterized with MAS or immune dysregulation
Measure: Classification of the immune function Time: ScreeningSpecific Aims: 1. The investigators will prospectively evaluate and analyze changes in the appearance of the lungs and heart through serial acquisition of focused point-of-care ultrasound images in a cohort of patients with or under investigation for COVID-19. 2. The investigators will correlate changes noted in ultrasound with clinical course and diagnostic evaluation to ascertain whether changes on ultrasound could improve care through earlier diagnosis or identification of patients at high risk of disease progression.
Description: POCUS is a 6-point scale evaluating the degree of abnormalities and number of sites with abnormalities in ultrasound images of the lungs. Higher scores indicate greater malady. Pulmonary POCUS Evaluation: B lines: absent (< 3 lines), present (> 3 lines), fused Consolidation: yes or no a. Bilateral: yes or no Pleural Effusion: yes or no Other pleural abnormalities: yes or no Score each finding based on degree of abnormalities and number of sites with abnormalities
Measure: POCUS Score - Lungs Time: up to 14 daysDescription: POCUS is a 6-point scale evaluating the degree of abnormalities and number of sites with abnormalities in ultrasound images of the heart. Higher scores indicate greater malady. Cardiac POCUS Evaluation: Parasternal long axis Parasternal short axis Qualitative LVEF: Normal, hyperdynamic, mild-moderately depressed, severely depressed EPSS (E-point septal separation): normal (<10 mm), abnormal (>10 mm) Left ventricular (LV) mass approximation by septal thickness Left Ventricular Chamber Size by internal diameter at diastole Score each finding based on degree of abnormalities and number of sites with abnormalities
Measure: POCUS Score - Heart Time: up to 14 daysSince December 2019, a new agent, the SARS-Cov-2 coronavirus has been rapidly spreading from China to other countries causing an international outbreak of respiratory illnesses named COVID-19. In France, the first cases have been reported at the end of January with more than 60000 cases reported since then. A significant proportion (20-30%) of hospitalized COVID-19 patients will be admitted to intensive care unit. However, few data are available for this special population in France. We conduct a large observational cohort of ICU suspected or proven COVID-19 patients that will enable to describe the initial management of COVID 19 patients admitted to ICU and to identify factors correlated to clinical outcome.
Description: Mortality at day 28
Measure: Mortality at day 28 Time: day 28Description: severe complications (pulmonary embolism, acute kidney injury, myocarditis, cardiac arrest, liver failure, ventilator associated pneumonia) Yes / No
Measure: severe complications Time: up to day 28Description: Delay in imaging in hours
Measure: Imaging Time: day 1Description: delay in microbiological diagnosis in hours
Measure: Delay in Microbiological diagnosis Time: day 1Description: Antiviral therapy Yes / no
Measure: Antiviral therapy Time: up to day 28Description: Antibiotic therapy Yes / No
Measure: Antibiotic therapy Time: day 28Description: Covid-19 treatments Yes / No
Measure: Covid-19 treatments Time: up to day 28Description: number
Measure: Patients receiving renal replacement therapy Time: up to day 28Description: number
Measure: Patients receiving mechanical ventilation Time: up to day 28Description: Patient alive at day 28 : yes / No
Measure: Vital status Time: day 28The purpose of this research is to identify whether or not Angiotensin Receptor Blockers (ARB) can halt the progression to respiratory failure requiring transfer into the intensive care unit (ICU), as well as halt mechanical ventilation in subjects with mild to moderate hypoxia due to the corona virus that causes COVID-19. Based on previous animal studies, the researchers hypothesize that the addition of an ARB is beneficial in abating acute lung injury in subjects in early stages of SARS-CoV-2 viral induced hypoxia.
Description: Number of subjects requiring transfer into ICU for mechanical ventilation due to respiratory failure
Measure: Mechanical ventilation Time: from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 daysDescription: Number of subjects transferred from non-ICU bed to an ICU bed
Measure: ICU transfer Time: from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 daysDescription: Number of days requiring oxygen therapy
Measure: Oxygen therapy Time: from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 daysThe COVID-19 pandemic has already overwhelmed the sanitary capacity. Additional therapeutic arsenals, albeit untested in the given context but previously proven to be efficacious in a related clinical context, that could reduce the morbidity rate are urgently needed. A decrease of Heart Rate Variability (HRV) is a validated bad prognosis marker in sepsis and acute respiratory distress syndrome. In contrast, auricular vagus nerve stimulation was proven not only to increase HRV values in healthy Humans, but also to reduce sepsis and increase survival, both significantly, in experimental models. Moreover, the heavy viral infection within the brainstem of deceased patients suggests that the neuroinvasive potential of SARS-CoV2 is likely to be partially responsible for COVID-19 acute respiratory failure and may bear relevance in tailoring future treatment modalities. Interestingly, the vagus nerve (or tenth cranial nerve) connects bidirectionally the brainstem to various internal organs including the lung and to one external organ, namely, the outer ear. Hence, the impact of auricular vagus nerve stimulation through semi-permanent needles will be studied, mostly used so far for pain alleviation, on the outcome of COVID-19 inpatients within 15 days.
Description: Inpatients are considered as clinically improved if they have gained at least 2 points on the following clinical evaluation scale, or if they went back home Clinical evaluation scale :1. Outpatient back to normal activities / 2. Outpatient without normal activities / 3. Inpatient without oxygen therapy / 4. Inpatient with oxygen therapy/ 5. Inpatient requiring either nasal high-flow oxygen therapy or non-invasive respirator or both / 6. Inpatient, requiring either ExtraCorporeal Membrane Oxygenation (ECMO) or invasive artificial respirator, or both / 7. Deceased.
Measure: Comparison of the percentage of clinically improved inpatients between D0 and D14 Time: 14 day after interventionThis is a prospective, multi-site study designed to evaluate whether the use of hydroxychloroquine in healthcare workers (HCW), Nursing Home Workers (NHW), first responders (FR), and Detroit Department of Transportation bus drivers (DDOT) in SE, Michigan, can prevent the acquisition, symptoms and clinical COVID-19 infection The primary objective of this study is to determine whether the use of daily or weekly oral hydroxychloroquine (HCQ) therapy will prevent SARS-CoV-2 infection and COVID-19 viremia and clinical COVID-19 infection healthcare workers (HCW) and first responders (FR) (EMS, Fire, Police, bus drivers) in Southeast Michigan. Preventing COVID-19 transmission to HCW, FR, and Detroit Department of Transportation (DDOT) bus drivers is a critical step in preserving the health care and first responder force, the prevention of COVID-19 transmission in health care facilities, with the potential to preserve thousands of lives in addition to sustaining health care systems and civil services both nationally and globally. If efficacious, further studies on the use of hydroxychloroquine to prevent COVID-19 in the general population could be undertaken, with a potential impact on hundreds of thousands of lives.
Description: We will measure the difference in new cases of COVID-19 disease between randomized treatment arms. Plan statistical analyses will include the assumption that up 10% of HCW at risk will become infected if no prophylactic treatment is provided. Therefore we expect that HCQ treatment arm will provide a reduction in the number of SARS-CoV 2 infections by 30%, with an expected study retention rate of 90%, a sample size of ~1500 participants per group, will have an 80% power to detect the difference at p=0.05.
Measure: To determine if the use of hydroxychloroquine as preventive therapy decreases the rate of acquisition of SARS-CoV 2 infections and clinical COVID-19 disease in Study Participants for each randomized treatment arm as compared to placebo. Time: 8 WeeksDescription: Compare the rates of SARS-CoV 2 infections between the randomized treatment arms and the control arms to determine the effect of HCQ dose in the prevention of COVID-19 viremia and disease as determined by study visits, weekly questionnaires, and blood samples.
Measure: Determine the effect of hydroxychloroquine dose in the prevention of COVID-19 viremia and disease. Time: 8 WeeksDescription: Comparison of the rates of SARS-CoV 2 infections in the non-randomized comparator arm to the randomized groups to assess the impact of chronic weight-based dosing of HCQ for COVID-19 prevention via weekly questionnaire and/or blood samples.
Measure: Assess the impact of chronic weight-based dosing of HCQ for COVID-19 prevention. Time: 8 WeeksDescription: Measurement of the rate of SARS-CoV 2 infections as measured by IgM/IgG seroconversion in study participants receiving randomized HCQ versus placebo via blood samples.
Measure: Comparison of the rate of SARS-CoV 2 infections as measured by IgM/IgG seroconversion in study participants receiving randomized HCQ versus placebo. Time: 8 WeeksDescription: Measurement of the seroprevalence of SARS-CoV 2 IgM/IgG positive samples at study entry and study conclusion in all participants receiving HCQ compared to those receiving placebo via blood samples.
Measure: Compare the seroprevalence of SARS-CoV 2 IgM/IgG positive samples at study entry and study conclusion in all participants receiving HCQ compared to those receiving placebo. Time: 8 WeeksDescription: Measurement of the emergence of clinical symptoms or COVID-19 diagnosis in participants presenting asymptomatically at study entry but identified as seropositive by serology at entry between the randomized treatment arms and comparator arm and via weekly questionnaire and/or blood samples.
Measure: Comparison of the emergence of clinical symptoms or COVID-19 diagnosis in participants presenting asymptomatically at study entry but identified as seropositive by serology at entry between the randomized treatment arms and comparator arm. Time: 8 WeeksDescription: Review of the level of care needed by participants in each arm developing COVID19 as measured as requiring emergency room visit, hospitalization or able to stay home without hospital care via weekly questionnaire.
Measure: To examine the level of care needed by participants in each arm developing COVID19 as measured as requiring emergency room visit, hospitalization or able to stay home without hospital care. Time: 8 WeeksDescription: Measurement of the safety and tolerability of HCQ dosing for preventive strategy against COVID-19 as measured by adverse events and serious adverse events reported via weekly questionnaire.
Measure: Determine the safety and tolerability of HCQ dosing for preventive strategy against COVID-19 as measured by adverse events and serious adverse events. Time: 8 WeeksDescription: Examination of other clinical determinants contributing to the risk of SARS-CoV 2 infection including demographics, work type and location, positive COVID-19 partners, possible exposures and clinical symptoms via study visits and weekly questionnaire.
Measure: To examine other clinical determinants contributing to the risk of SARS-CoV 2 infection in healthcare workers and first responders. Time: 8 WeeksDescription: Examine the association between HCQ drug levels and development of COVID-19 symptoms or positive test results via weekly questionnaire and/or blood samples.
Measure: Examine the association between HCQ drug levels and development of COVID-19 symptoms or positive test results. Time: 8 WeeksDescription: Identification of immunologic, serological and inflammatory markers associated with acquisition and response to COVID-19 in both HCQ and placebo Participants developing laboratory or clinical confirmed disease via study visits, weekly questionnaire, and blood samples.
Measure: identify immunologic, serological and inflammatory markers associated with acquisition and response to COVID-19 in both HCQ and placebo Participants developing laboratory or clinical confirmed disease. Time: 8 weeksCoronaviruses (CoV) are positive-sense single-stranded RNA viruses that infect a wide range of hosts producing diseases ranging from the common cold to serious / fatal events. Nitazoxanide (NTZx) is a derivative of 5-nitrothiazole, synthesized in 1974 by Rosignol - Cavier. NTZx has powerful antiviral effects through the phosphorylation of protein kinase activated by double-stranded RNA, which leads to an increase in phosphorylated factor 2-alpha, an intracellular protein with antiviral effects. The purpose of this study is to contrast the beneficial effect of NTZx vs NTZx plus hydroxychloroquine in patients Coronavirus Disease (COVID-19) as well as against other treatments.
Description: Percentage of patients COVID-19 positive that required mechanical ventilation
Measure: Mechanical ventilation requirement Time: Since the diagnosis until two weeks afterCoronavirus disease 2019 (COVID-19) is an infectious disease responsible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is highly contagious requiring restrictive and stressful measures for patients, family members and ICU healthcare providers. To avoid contagion, patient isolation has become the rule. For patients, these measures add stress to the ICU environment and deprive them of unrestricted family visits. Family members are not only left with fear but also many unanswered questions. In end-of-life situations, many family members are unable to say good-bye and unable to provide support to their loved-one throughout the process. The impact of exclusion or limited inclusion certainly needs to be explored. Moreover, ICU caregivers are having to face new challenges and to work in a unknown situation, juggling with both professional issues such as increased workload, working longer hours and safety issues, and personal issues such as child care and transport as well as family transmission of the virus. The main objective of this study is to demonstrate that the COVID-19 pandemic, as compared to seasonal flu and community acquired pneumonia, significantly increases post-traumatic stress disorder (PTSD) in family members of critically ill patients. PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge. The IES-R is a 22-item self-report measure that assesses subjective distress caused by traumatic events. It will be compared across the three groups (COVID-19, FLU and CAP).
Description: Proportion of Family members with IES-R> 22 PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge of corresponding patient. It si a scale ranging from 0 to 88. Weiss, DS.; Marmar, CR. The impact of event scale - revised. In: Wilson, JP.; Keane, TM., editors.Assessing psychological trauma and PTSD. New York: Guilford Press; 1997. p. 399-411
Measure: PTSD Family members sup 22 Time: 90 daysDescription: Among Family members PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)
Measure: PTSD Family members Time: 90 daysDescription: Among Patients PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)
Measure: PTSD Patients Time: 90 daysDescription: Among healthcare providers PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)
Measure: PTSD healthcare providers Time: 2 months after official end of the Covid-19 peakDescription: Among Family members Symptoms of anxiety and depression using the HADS scale
Measure: HADS Family members Time: 90 daysDescription: Among Patients Symptoms of anxiety and depression using the HADS scale
Measure: HADS Patients Time: 90 daysDescription: Among Patients Mental and physical health-related quality of life as assessed by the SF36
Measure: SF36 Patients Time: 90 daysDescription: Among Family members Questionnaire describing their experience of the patient's ICU hospitalization
Measure: Questionnaire Family members Time: 90 daysDescription: Among Patients Questionnaire describing their experience of the patient's ICU hospitalization
Measure: Questionnaire Patients Time: 90 daysDescription: Among healthcare providers Questionnaire describing their experience of the patient's ICU hospitalization
Measure: Questionnaire healthcare providers Time: 2 months after official end of the Covid-19 peakDescription: Among healthSymptoms of burnout on MBI scale as assessed by the Maslash Burnout Inventorycare providers
Measure: MBI healthcare providers Time: 2 months after official end of the Covid-19 peakDescription: Job Strain as assessed by the Karasec instrument
Measure: Karasec instrument healthcare providers Time: 2 months after official end of the Covid-19 peakThe overall objective of the study is to determine the therapeutic effect and tolerance of Anakinra in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Anakinra (ANA) is a recombinant human decoy IL-1Ra and therefore blocks IL-1α and IL-1β. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Anakinra administration to patients enrolled in the COVIMUNO-19 cohort. Anakinra will be administered to consenting adult patients hospitalized with CORVID-19 either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or critical pneumonia requiring mechanical ventilation. Patients who will chose not to receive Anakinra will receive standard of cares. Outcomes of Anakinra -treated patients will be compared with outcomes of standard of care treated patients as well as outcomes of patients treated with other immune modulators.
Description: Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
Measure: Survival without needs of ventilator utilization at day 14 Time: 14 daysDescription: Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5.
Measure: WHO progression scale ≤ 5 Time: 4 daysDescription: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.
Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) or withdrawal of NIV or high flow (for > 48h), at day 14 Time: 14 daysDescription: Proportion of patients with a decrease of WHO score of at least 1 point at day 4
Measure: Decrease of at least one point in WHO progression scale score Time: 4 daysDescription: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10.
Measure: WHO progression scale Time: 7 and 14 daysDescription: Overall survival.
Measure: Survival Time: 14, 28 and 90 daysDescription: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours.
Measure: Respiratory acidosis Time: 4 daysDescription: Evolution of PaO2/FiO2 ratio.
Measure: PaO2/FiO2 ratio Time: day 1 to day 14Description: Time to oxygen supply independency.
Measure: Time to oxygen supply independency Time: 14 daysDescription: Duration of hospitalization.
Measure: Duration of hospitalization Time: 90 daysDescription: Time to negative viral excretion.
Measure: Time to negative viral excretion Time: 90 daysDescription: Time to ICU discharge.
Measure: Time to ICU discharge Time: 90 daysDescription: Time to hospital discharge.
Measure: Time to hospital discharge Time: 90 daysThis Phase III trial four treatment strategies non-critically ill hospitalized participants (not requiring ICU admission and/or mechanical ventilation) with SARS CoV-2 infection, Participants will receive hydroxychloroquine or chloroquine with or without azithromycin.
Description: Time (hours) from randomization to recovery defined as 1) absence of fever, as defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications AND 2) absence of symptoms of greater than mild severity for 24 hours AND 3) not requiring supplemental oxygen beyond pre-COVID baseline AND 4) freedom from mechanical ventilation or death
Measure: Hours to recovery Time: 42 daysDescription: Time to resolution of fever defined as at least 48 hours since last temperature ≥ 38.0°C without the use of fever-reducing medications
Measure: Time fever resolution Time: 42 daysThe purpose of this research is to see if the DPP4 inhibitor linagliptin, an oral medication commonly used to treat type 2 diabetes,can help with diabetes control and reduce the severity of the COVID-19 infection
Description: Change in glucose control will be assessed via glucose levels obtained from blood serum samples
Measure: Changes in Glucose Llevels Time: Baseline, up to 2 weeksDescription: changes in SpO2 will be measured with a Pulseimetry, an indirect, non-invasive method
Measure: Changes in SpO2 levels Time: Baseline, up to 2 weeksDescription: Changes in IL 6 will be assessed from blood serum samples
Measure: Changes in Interleukin 6 (IL6) Time: Baseline, up to 2 weeksDescription: Changes in Chest radiography (X-ray)
Measure: Changes in chest structures Time: Baseline, up to 2 weeksThe Coronavirus Disease 2019 (COVID-19) pandemic has placed tremendous stress on the global economy since its outbreak in December 2019. Currently, with nearly 1.3 million confirmed cases, there is still no effective way to contain the disease. The transmission of COVID-19 occurs via direct (prolonged close interaction, within 2 meters for more than 30 minutes) and indirect (fomites) contacts. Locally, the risk of COVID-19 infection in household contacts of confirmed cases is about 4%. These at-risk individuals are identified through contact tracing and infectious may be preventable using post-exposure-prophylaxis (PEP). However, there has yet to be a single effective, safe, and affordable pharmacological agent with such capabilities. Hydroxychloroquine (HCQ) is a cheap anti-malarial and immunomodulatory agent which may potentially be used as PEP against COVID-19. HCQ is capable of blocking the invasion and intracellular replication of the virus. Existing studies have reported efficacy of HCQ in treating COVID-19, with reduced time to clinical recovery and few reports of patients suffering from significant side effects. However, existing studies are largely limited by their small sample sizes. Furthermore, there has yet to be a published trial on HCQ's role in PEP. This cluster randomized trial will evaluate the safety and efficacy of oral HCQ PEP, taken over for 5 days, in reducing the number of infected household contacts of confirmed COVID-19 patients under home quarantine. Comparison will be made between HCQ PEP (treatment group) and no treatment (control group). Subjects will be followed up over a course of 28 days, with daily symptom monitoring conducted over phone calls. Positive outcomes from this study will provide a means for us to battle the COVID-19 pandemic.
Description: COVID-19 infection
Measure: positive serology or reverse transcriptase (RT-PCR) for COVID-19 up until day 28. Time: Until day 28Description: Serology
Measure: Positive serology at day 28. Time: 28 daysDescription: COVID-19
Measure: Symptoms of COVID-19. Time: Until day 28A novel coronavirus, SARS-CoV-2, is responsible for a rapidly spreading pandemic that has reached 160 countries, infecting over 500,000 individuals and killing more than 24,000 people. SARS-CoV-2 causes an acute and potentially lethal respiratory illness, known as COVID-19, that is threatening to overwhelm health care systems due to a dramatic surge in hospitalized and critically ill patients. Patients hospitalized with COVID-19 typically have been symptomatic for 5-7 days prior to admission, indicating that there is a window during which an effective intervention could significantly alter the course of illness, lessen disease spread, and alleviate the stress on hospital resources. There is no known treatment for COVID-19, though in vitro and one poorly controlled study have identified a potential antiviral activity for HCQ. The rationale for this clinical trial is to measure the efficacy and safety of hydroxychloroquine for reducing viral load and shedding in adult outpatients with confirmed COVID-19.
Blood samples from participants who have recovered from COVID-19 infection will be obtained and studied. The goal of the research is to identify antibodies that have been generated by the patient to fight the COVID-19 infection. By identifying the most effective antibodies, scientists can make specific antibodies to use to prevent future coronavirus outbreaks or to treat patients with severe disease.
Description: The blood specimen will be proceeded into peripheral blood mononuclear cells and plasma to be stored for testing. In brief, CD27+ memory B cells that can bind to a SARS-CoV-2 S protein bait will be sorted by flow cytometry and RNA will be extracted to obtain heavy and light chain sequences. Antibody sequences will be annotated using bioinformatics approaches, and candidate sequences will be cloned. Purified antibodies will be characterized and neutralization breadth and potency against SARS-CoV-2 and other related coronaviruses will be assessed using neutralization assays.
Measure: Number of antibodies against coronaviruses isolated and identified from patient samples Time: Up to 12 months after collection visitThis is a double-blind, randomized, placebo-controlled clinical trial. A total of 210 individuals aged over 18 years old, without a diagnosis of severe respiratory disease, who came to the study site with clinical and radiological suspicion of SARS-CoV2, will be randomized into two treatment groups at a 1:1 ratio to receive a 5-day CQ diphosphate tablets or placebo (tablet without active ingredient produced with the same physical characteristics).
Description: Evaluate if CQ diphosphate prevents the onset of SARS in patients on intervention group through standardized questionnaires.
Measure: Proportion of patients with onset of severe acute respiratory syndrome (SARS) Time: 7 days after randomizationDescription: Mortality rate between intervention and placebo group on days 7, 14, and 28 after randomization
Measure: Mortality rate Time: after randomization, up to 28 daysDescription: Proportion of participants in need and duration of intensive care support after randomization
Measure: Number of participants in need of intensive care support Time: during and after intervention, up to 28 daysDescription: Viral load change in blood and oropharyngeal swab samples
Measure: Viral concentration Time: After randomization, up to 7 daysDescription: Incidence of serious adverse events during and after treatment
Measure: Cumulative incidence of serious adverse events Time: During and after intervention, up to 28 daysDescription: Incidence of grade 3 and 4 adverse events during and after treatment
Measure: Cumulative incidence of grade 3 and 4 adverse events Time: During and after intervention, up to 28 daysDescription: proportion of discontinuation or temporary suspension of treatment (for any reason)
Measure: Proportion of patients with discontinued treatment Time: after randomization, up to 28 daysDescription: proportion of patients with increased levels of troponin I
Measure: Incidence of cardiac lesions Time: after randomization, up to 120 daysDescription: proportion and magnitude of QTcF interval increases higher than 500ms
Measure: Incidence of cardiac disfunctions Time: after randomization, up to 120 daysDescription: Changes measured on day 120 will be compared to baseline, through spirometry.
Measure: Change in respiratory capacity Time: Day 120 after randomizationThe purpose of this study is to examine the impact of ascorbic acid (vitamin c) and zinc gluconate in reducing duration of symptoms in patients diagnosed with coronavirus disease 2019 (COVID-19). Patients above the age of 18 who present to the Cleveland Clinic outpatient testing and receive a positive test for COVID-19 will be invited to participate.
Description: Outpatients who test positive for the Coronavirus 2019; number of days required in which they reach a 50 percent reduction in the cumulative 0-12 score symptom category of fever based on a 0-3 scale: 0 = ≤98.6, 1 = >98.6- 100.6, 2 = > 100.6 - 102.6, 3 = >102; Cough on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe; Shortness of Breath on a 0-3: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with walking on flat surface 3 = short of breath with getting dressed or daily activities; and Fatigue on a 0-3 scale: 0 = No fatigue/energetic, 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue. Each patient will have a composite score ranging from 0-12/day
Measure: Symptom Reduction Time: 28 daysDescription: The number of days required to reach a score of 0 from the symptom category of fever based on a 0-3 scale: 0 = ≤98.6, 1 = >98.6- 100.6, 2 = > 100.6 - 102.6, 3 = >102.6
Measure: Symptom Resolution: Fever Time: 28 daysDescription: The number of days required to reach a score of 0 from the symptom category of cough based on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe
Measure: Symptom Resolution: Cough Time: 28 daysDescription: The number of days required to reach a score of 0 from the symptom category of shortness of breath based on a 0-3 scale: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with walking on flat surface 3 = short of breath with getting dressed or daily activities
Measure: Symptom Resolution: Shortness of Breath Time: 28 daysDescription: The number of days required to reach a score of 0 from the symptom category of fatigue based on a 0-3 scale: 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue.
Measure: Symptom Resolution: Fatigue Time: 28 daysDescription: Total symptom composite score at day 5 of study supplementation: Symptom categories of fever based on a 0-3 scale: 0 = ≤98.6, 1 = >98.6- 100.6, 2 = > 100.6 - 102.6, 3 = >102; Cough on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe; Shortness of Breath on a 0-3: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with walking on flat surface 3 = short of breath with getting dressed or daily activities; and Fatigue on a 0-3 scale: 0 = No fatigue/energetic, 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue.
Measure: Day 5 Symptoms Time: 5 daysDescription: Differences in hospitalization events between the study arms
Measure: Hospitalizations Time: 28 daysDescription: Differences in severity of symptoms between study arms
Measure: Severity of Symptoms Time: 28 daysDescription: Differences in number of patients who were prescribed adjunctive medications for their diagnosis between study arms
Measure: Adjunctive Medications Time: 28 daysDescription: Differences in number of patients in study arms who experienced side effects from the supplements.
Measure: Supplementation Side Effects Time: 28 daysThe present study is ideated to prospectively investigate in patients with severe acute respiratory syndrome (SARS) due to Coronavirus 19 (SARS-Cov-2) infection and moderate-severe respiratory failure the patterns and changes in platelet reactivity, thrombotic status and endothelial function. The observed patterns and changes will be related with inflammatory status, myocardial injury and outcomes
Description: patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli
Measure: on-treatment platelet reactivity Time: early stage of disease (first 96 hours)Description: patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli
Measure: on-treatment platelet reactivity Time: mid stage of disease (96 hours - 14 days)Description: patterns and changes of platelet aggregation values assessed by light transmission aggregometry after arachidonic acid, adenosine diphosphate and thrombin receptor activating peptide stimuli
Measure: on-treatment platelet reactivity Time: late stage of disease (>14 days)Description: patterns and changes of the rate of apoptosis in HUVEC incubated with serum from patients enrolled in the study.
Measure: apoptosis rate in human umbilical vein endothelial cells (HUVEC) Time: early stage of disease (first 96 hours)Description: patterns and changes of the rate of apoptosis in HUVEC incubated with serum from patients enrolled in the study.
Measure: apoptosis rate in human umbilical vein endothelial cells (HUVEC) Time: mid stage of disease (96 hours - 14 days)Description: patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.
Measure: Nitric oxide (NO) intracellular levels Time: late stage of disease (>14 days)Description: patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.
Measure: Nitric oxide (NO) intracellular levels Time: early stage of disease (first 96 hours)Description: patterns and changes of intracellular level of NO in HUVEC incubated with serum from patients enrolled in the study.
Measure: Nitric oxide (NO) intracellular levels Time: mid stage of disease (96 hours - 14 days)Description: patterns and changes of ROS
Measure: reactive oxygen species (ROS) levels Time: early stage of disease (first 96 hours)Description: patterns and changes of ROS
Measure: reactive oxygen species (ROS) levels Time: mid stage of disease (96 hours - 14 days)Description: patterns and changes of ROS
Measure: reactive oxygen species (ROS) levels Time: late stage of disease (>14 days)Description: patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)
Measure: coagulation factors levels Time: early stage of disease (first 96 hours)Description: patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)
Measure: coagulation factors levels Time: mid stage of disease (96 hours - 14 days)Description: patterns and changes of the most important coagulation factors (i.e. tissue factor antigen pg/dL)
Measure: coagulation factors levels Time: late stage of disease (>14 days)Description: values of FEV1% as assessed by spirometry
Measure: respiratory function Time: 6-monthDescription: values of FEV1% as assessed by spirometry
Measure: respiratory function Time: 12-monthDescription: values of left ventricular ejection fraction as assessed by transthoracic echocardiogram
Measure: cardiac function Time: 6-monthDescription: values of left ventricular ejection fraction as assessed by transthoracic echocardiogram
Measure: cardiac function Time: 12-monthDescription: occurrence of death, myocardial infarction, stroke and other major adverse events
Measure: clinical outcome Time: 12-monthThis is a double-blind, randomized, placebo-controlled, phase IIb clinical trial to assess the efficacy and safety of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 420 individuals of both sexes, aged over 18 years old, with symptoms suggestive or confirmed diagnosis of severe acute respiratory syndrome (SARS), hospitalized at the Hospital and Pronto-Socorro Delphina Rinaldi Abdel Aziz (HPSDRAA), with clinical and radiological findings suggestive of SARS-CoV2 infection, will be randomized at a 1:1 ration to receive either MPS (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).
Description: Mortality rate on day 28, after randomization
Measure: Mortality rate at day 28 Time: on day 28, after randomizationDescription: Number of patients with diagnosis of early onset of SARS
Measure: Proportion of patients with SARS Time: after randomization, up to 7 days.Description: Proportion of patient that died on days 7, 14 and 28.
Measure: Mortality rate on days 7, 14 and 28 Time: after randomization, up to 28 days.Description: proportion of patients requiring orotracheal intubation
Measure: Incidence of orotracheal intubation Time: after randomization, up to 7 days.Description: Proportion of patients with oxygenation index (PaO2 / FiO2) < 100 in 7 days.
Measure: Change in oxygenation index Time: after randomization, up to 7 days.Multicenter observational/registry study of the clinical features and outcomes of critically ill patients with COVID-19.
The prone position consists of placing the patient on his or her stomach with the head on the side, during sessions lasting several hours a day and could help spontaneous ventilate the patient.
Description: PaO2 improvement of more than 20% after one hour in prone position in spontaneously breathing non intubated COVID-19 patients.
Measure: Proportion of "responder" patients to prone position Time: 1 hourDescription: PaO2 improvement of more than 20% at 6 to 12 hours from return to supine position.
Measure: proportion of "persistent responders" patients after prone position Time: 1 dayDescription: PaO2 at 1 hour from the start of prone position and at 6 to 12 hours afterreturn to supine position.
Measure: Evolution of PaO2 Time: 1 dayDescription: Look for an association between the time spent in Prone positione and persistent responder or not;
Measure: Duration of prone positioning and PaO2 evolution Time: 2 daysDescription: proportion of patients improving their arterial saturation within 1 hour of Prone Position
Measure: Evolution of Spo2 Time: 1 hourDescription: evolution of the EVA scores for dyspnea at 1 hour from the start of the Prone Position and at 6 hours after the end of the Prone Position
Measure: EVA Dyspnea Time: 1 dayDescription: proportion of patients intolerant to prone position (Prone Position <1h);
Measure: Intolerance to prone positioning Time: 1 dayDescription: proportion of patients who can maintain prone position for more than 3 h.
Measure: Tolerance to prone positioning Time: 1 dayCCAP is an investigator-initiated multicentre, randomized, double blinded, placebo-controlled, multi-stage trial, which aims to assess the safety and efficacy of novel treatment option of moderate-severe COVID-19. Participants will be randomized 1:1:1:1:1:1 to parallel treatment arms: Convalescent plasma, sarilumab, hydroxychloroquine, baricitinib, intravenous and subcutaneous placebo, or oral placebo. Primary outcome is a composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days.
Description: Composite outcome
Measure: All-cause mortality or need of invasive mechanical ventilation Time: 28 daysDescription: Number of participants with adverse events with possible relation to study drug
Measure: Frequency of adverse events Time: 90 daysDescription: Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines
Measure: Frequency of severe adverse events Time: 90 daysDescription: Number of days to improvement of at least 2 categories relative to baseline on the ordinal scale. Categories are as follows: Death; Hospitalized, in intensive care requiring Extracorporeal Membrane Oxygenation (ECMO) or mechanical ventilation; Hospitalized, on non-invasive ventilation or high-flow oxygen device; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities
Measure: Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status Time: 90 daysDescription: Number of days without mechanical ventilation
Measure: Ventilator-free days Time: 28 daysDescription: Number of days without organ-failure
Measure: Organ failure-free days Time: 28 daysDescription: Number of days in ICU
Measure: Duration of ICU stay Time: 90 daysDescription: Number of deaths by any cause
Measure: Mortality rate Time: 7, 14, 21, 28 and 90 daysDescription: Days from the date of hospital admission for COVID-19 to the date of discharge
Measure: Length of hospital stay Time: 90 daysDescription: Days requiring supplement oxygen
Measure: Duration of supplemental oxygen Time: 90 daysDouble blinded randomized clinical trial designed to evaluate the efficacy and safety of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with confirmed COVID-19 pneumonia.
Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points (score range from 1 to 7 , with 7 being the worst score)
Measure: Time to clinical improvement of at least 1 level on the ordinal scale between Day 1 (day of the first administration of study drug) to Day 11 (day after last day of treatment). Time: up to Day 11Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points at day 15 and day 29
Measure: Clinical status assessed by ordinal scale Time: up to Day 29Description: Necessity for transfer to Intensive care unit
Measure: transfer to ICU Time: up to Day 29Description: days from admission to hospital discharge
Measure: Length of hospital day Time: up to Day 29Description: incidence of all-cause mortality
Measure: Hospital Mortality Time: Day 29Description: Need to mechanical ventilation
Measure: Need to Mechanical Ventilation Time: up to Day 29Description: adverse reactions
Measure: Occurence of grade 3-4 adverse event Time: up to Day 29Description: ECG
Measure: QTc Lengthening Time: up to Day 11Description: Thoracic CT scan : number and size of ground-glass opacifications on day 1 and day 11 Two independent pulmonary imagery experts will assess abnormalities according to a standardized framework
Measure: Evolution of pulmonary CT scan images Time: up to Day 11The 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID 19), which originated in Wuhan, China, has become a major concern all over the world. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite any attempted treatment.. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease. The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Plasma-exchange is expensive and requires large volumes of substitution fluid. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion. With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The aforementioned limitations of plasma therapy can be overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP).DFPP is a modality of plasma purification that performs an initial plasma separation from blood, and the subsequent separation of specific molecules, on the basis of their specific molecular weight (cut-off), by using a fractionation filter. The Fractionation Filter 2A20, because of its membrane sieving cut-off, retains larger molecules and returns plasma along with smaller molecules to the circulation, including the major part of the albumin. The selection of the membrane 2A20 is related to the appropriate Sieving Coefficient for IgG that allows to efficiently collect antibodies from patients which are recovered from COVID-19, with negligible fluid losses and limited removal of albumin. The total amount of antibodies obtained during one DFPP session exceeds by three to four times the total amount provided to recipients with one unit of plasma obtained during one plasma-exchange session from one COVID-19 convalescent donor. This should result in more effective viral inhibition and larger benefit for the patient achieved with one unit of enriched immunoglobulin solution obtained with DFPP than with one unit of plasma obtained with plasma exchange. These observations provide the background for a pilot study aimed to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for critically ill patients with severe coronavirus (COVID-19) pneumonia requiring mechanical ventilation.
To create a protocol for treatment of Pakistani patients with SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different quinone drug dosing regimens in controlling SARS-CoV-2 infection for asymptomatic patients.
Description: Percentage of patients who become RT-PCR negative with two RT-PCR tests performed at day 6 and day 7
Measure: RT-PCR negative status Time: 6-7 daysDescription: Time to progression to next stage of SARS-CoV-2 disease severity index
Measure: Progression of symptoms Time: 7 daysDescription: Time to onset of fever (temperature greater than 100 degree F), cough, or shortness of breath (respiratory rate >22 per minute).
Measure: Development of Symptoms Time: 7 daysDescription: Drug related adverse events as determined by data safety and monitoring board (DSMB)
Measure: Adverse events Time: 7 daysTo evaluate the effectiveness of Nigella Sativa/ Black Cummins (1gm seed powder in a capsule orally) and 30ml of honey stirred in 250ml of distilled water 12 hourly till patient becomes asymptomatic or a maximum of 14 days with standard hospital care vs standard hospital care alone with placebo capsule and 250ml water, in clearing the COVID-19 nucleic acid from throat and nasal swab, lowering disease detrimental effects on HRCT chest/X-ray and severity of symptoms along with duration of hospital stay till day 14th day of follow up and 30 days mortality (primary outcomes).
Description: RT-PCR will be done on admission day (0 day) and then after every 4th day for 14 days or till the symptoms resolved and RT-PCR gets negative. RT-PCR will only be shown as positive or negative (as per limitation of Pakistan).
Measure: Days required to get a positive COVID-19 PCR to negative Time: upto max 14 daysDescription: HRCT will be conducted at admission day (0-day) and a total of maximum four CT-scan will be conducted after every 4th day. The minimum and score at which we label covid-19 positive will be 5 and 25 respectively using internationally standard nomenclature as described by Fleischner Society glossary and peer-reviewed literature on viral pneumonia.
Measure: HRCT/ X-ray findings of disease progression Time: upto max 14 daysDescription: Clinically disease progression will be evaluated depending upon the severity of symptoms being classified as mild, moderate and severe.
Measure: Severity of symptoms progression Time: upto max 14 daysDescription: Duration of hospital stay would be categorized as the number of days the patient stayed in the ward during treatment. The date of admission and date of discharge would give us total duration of stay.
Measure: Duration of Hospital Saty Time: upto max 14 dayDescription: 30 days mortality rate in each arm
Measure: 30 day mortality Time: 30 daysDescription: every 4th day oxygen saturation at room air will be checked to evaluate the disease progression
Measure: Oxygen Saturation at room air Time: upto max of 14 daysDescription: Involvement of cardiac complications will be assessed
Measure: Incidence of viral myocarditis Time: upto max 14 daysDescription: Lethal complication like ARDS will be assessed to evaluate disease severity
Measure: Incidence of Acute respiratory Distress Syndrome Time: upto max 14 daysIt is unknown what proportion of healthy children have been exposed to SARS-Cov-2 and how many have antibodies. The aim of this study is to follow a cohort of healthy children over six months and measure their antibodies to SARS-CoV-2.
SARS-CoV-2 spreads rapidly throughout the world. A large epidemic would seriously challenge the available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Strategies to prevent infection and disease severity of HCW are, therefore, desperately needed to safeguard continuous patient care. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in in vitro and in vivo studies, and reported morbidity and mortality reductions as high as 70%. Furthermore, in our preliminary analysis, areas with existing BCG vaccination programs appear to have lower incidence and mortality from COVID191. The investigators hypothesize that BCG vaccination can reduce HCW infection and disease severity during the epidemic phase of SARS-CoV-2.
Description: The primary outcome measure is the development of COVID19 infection. We will use the Cox proportional-hazards model to calculate hazard ratios for the development of Covid-19. This will be reported as the proportion of individuals receiving the intervention who are PCR-positive or seroconvert. defined as number of new cases during the 6 month time period
Measure: Incidence of COVID 19 Infection Time: 6 monthsDescription: The secondary outcome measure is disease severity calculated using the Covid Severity Scale Scoring of 0 -10. A score of 10 is worse and a score of 0 is best. Disease severity score will be based on the level of care required for individuals who test positive for COVID19 as follows: non-hospital-based care; patient hospitalized but no oxygen required; hospitalized and oxygen required; patient treated in intensive care and/or on mechanical ventilation; patient died. Additional WHO criteria for severity include severe pneumonia, respiratory failure, acute respiratory distress syndrome, sepsis and septic shock.
Measure: Disease Severity Time: up to 6 monthsCOVID-19's mechanism to enter the cell is initiated by its interaction with its cellular receptor, the angiotensin-converting enzyme. As a result of this union, a clathrin-mediated endocytosis process begins. This route is one of the therapeutic targets for which available drugs are being investigated in order to treat COVID-19 infection. This is one of the mechanisms blocked by drugs like ruxolitinib and chloroquine. Various drugs approved for clinical use that block the clathrin-mediated endocytosis pathway have been explored. It has been found that the best in vitro and in vivo results were obtained with statins, which also allowed generating a greater potent adaptive immune response. Therefore, statins and specifically simvastatin make it possible to block the entry process used by COVID-19, block inflammation by various mechanisms and increase the adaptive immune response. All of these processes are desirable in patients infected with COVID-19. Statins have been proposed to have beneficial effects in patients infected with MERS-COV, another coronavirus similar to COVID-19, but there have been no randomized studies supporting the use of statins in patients with COVID-19 infection. In this project we propose the combined use of one of these drugs, ruxolitinib with simvastatin, looking for a synergistic effect in the inhibition of viral entry and in the anti-inflammatory effect.
Description: Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 7 from randomization.
Measure: Percentage of patients who develop severe respiratory failure. Time: 7 daysDescription: Patients achieving a grade 5 or higher of the WHO 7-point ordinal scale of severity categorization for COVID at day 14 from randomization.
Measure: Percentage of patients who develop severe respiratory failure. Time: 14 daysDescription: Time from ICU admision to ICU discharge.
Measure: Length of ICU stay. Time: 28 daysDescription: Time from hospital admision to hospital discharge.
Measure: Length of hospital stay Time: 28 daysDescription: Percentage of patients alive at 6 months
Measure: Survival rate at 6 months Time: 6 monthsDescription: Percentage of patients alive at 12 months
Measure: Survival rate at 12 months Time: 12 monthsDescription: Percentage of patients who died from any cause 28 days after inclusion in the study
Measure: Survival rate at 28 days Time: 28 daysDescription: Percentage of patients with each AE by grade in relation with total number of treated patients
Measure: Percentage of patients with each AE by grade Time: 28 daysDescription: Percentage of patients who discontinued due to AEs in relation with total number of treated patients
Measure: Percentage of patients who discontinued due to AEs Time: 28 daysThe main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo.
The purpose of this study is to determine how peoples' bodies respond to exposure to COVID-19. Employees of Beaumont Health in Michigan who are older than 18 years may be eligible to participate. Participants will have blood drawn two or more times for serology testing. This serology test will determine if participants have detectable levels of the antibodies that our bodies develop to fight COVID-19 infection. Participants will fill out a questionnaire each time they provide a blood sample. The questionnaires include questions about participants' personal traits; their health; general questions about their risk to exposure; job and risk of exposure; symptoms, diagnosis, treatment of COVID-19 since last blood draw. Researchers will monitor participants' medical records in a confidential manner for one year after the last blood draw to help determine if people who develop antibodies to COVID-19 are protected against developing a COVID-19 infection in the future.There may be no direct benefits for participants; however, information from this study may benefit other people by increasing our understanding of COVID-19, how it spreads from person to person, and how people respond to fight off the infection.The results of the serology test are used for research only and will not affect clinical decisions regarding participants' treatment or quarantine
Description: Serology testing of Beaumont Health employees will allow an estimation of asymptomatic carriage and help determine level of nosocomial spread of COVID-19 within our institution among its employees. All participants will provide over 2 blood draws between 2 and 4 weeks apart to determine if they developed antibodies to COVID-19. Participants at medium risk for exposure in their job function at Beaumont will have 3 draws 2-4 weeks apart and people considered the highest risk, those who provide the direct patient care to COVID-19 patients, will be tested 2-4 weeks apart until the pandemic in Michigan is under control (estimated to be 8 blood draws).
Measure: Prevalence COVID antibodies in employees of Beaumont Health Time: 1 yearThe objective of the study is to evaluate the efficacy of helmet NIV in reducing the duration of invasive mechanical ventilation in order to minimize ventilator needs during the COVID-19 pandemic.
Description: duration of mechanical ventilation via endotracheal tube
Measure: ventilator days Time: up to 4 weeksDescription: number of days admitted to the ICU
Measure: Intensive care unit (ICU) length of stay Time: up to 6 weeksDescription: number of patients requiring endotracheal intubation after extubation
Measure: need for re-intubation Time: up to 6 weeksDescription: number of days spent in hospital during enrollment hospitalization
Measure: hospital length of stay Time: up to 6 weeksDescription: death from any cause during hospitalization time of enrollment
Measure: hospital mortality Time: up to 6 weeksDescription: death from any cause 90 day, 1year
Measure: long term mortality Time: up to 1 yearDescription: including ventilator associated pneumonia, GI hemorrhage, DVT/PE, sacral decubitus ulcer, delirium, ICU acquired weakness
Measure: ICU related complications Time: up to 6 weeksDescription: measure the location (home, rehabilitation center, nursing home)
Measure: discharge location Time: up to 90 daysDescription: days alive and institution free
Measure: health care utilization Time: up to 6 weeksDescription: ultrasound measurement at end expiration: enrollment, pre extubation, post extubation
Measure: diaphragm ultrasound thickness Time: up to 6 weeksDescription: ultrasound measurement at end expiration and inspiration to calculate thickening fraction
Measure: diaphragm thickening fraction Time: up to 6 weeksThe aim of the COVI-PRONE Trial is to determine if early awake prone positioning in COVID-19 patients with hypoxemic respiratory failure; irrespective of the mode of oxygen delivery; reduces the need for invasive mechanical ventilation.
Description: Medical procedure in which a tube is placed into the windpipe (trachea) through the mouth.
Measure: Endotracheal intubation Time: within 30 days of randomizationDescription: Death
Measure: Mortality Time: 30 daysDescription: Number of days not receiving mechanical ventilation
Measure: Invasive mechanical ventilation free days Time: 30 DaysDescription: Number of days not receiving non-invasive mechanical ventilation
Measure: Non-invasive ventilation free days Time: 30 daysDescription: Number of days admitted to ICU
Measure: ICU length of stay Time: 30 DaysDescription: Number of days admitted to the hospital
Measure: Hospital length of stay Time: 30 daysDescription: defined as the difference in SpO2: FiO2 ratio. The difference in SpO2: FiO2 ratio.
Measure: Change in oxygenation Time: 30 daysDescription: Includes any of the following: accidental removal of intravenous access, vomiting, falls from bed, pressure injuries, or cardiac arrest.
Measure: Complications from proning, Time: 30 daysPatients with COVID-19 usually present in the ED and receive their initial medical check-up here. We will try to gather information of comorbidities and other conditions at the time of presentation of COVID-19 patients to the ED. The course of the disease prior to admission as well as the momentary health status at presentation to the ED are of interest because they influence risk stratification and decision-making of treating physicians. The ratio of patients with mild or moderate to severe symptoms will help to calculate the need for hospital beds including beds on Intensive Care Units (ICU) and Intermediate Care Units (IMC), as well as the need for other hospital resources.
Description: Identification of risk factors present at the earliest stage of hospital care (i.e. in the ED) that warrant hospital admission.
Measure: Identification of risk factors present at the earliest stage of hospital care (i.e. in the ED) that warrant hospital admission. Time: 6 monthsDescription: Determination of the course of the disease (days since onset of symptoms, nature of symptoms, e.g. fever, chills, headache) and the state at which patients present to the ED
Measure: Determination of the course of the disease (days since onset of symptoms, nature of symptoms, e.g. fever, chills, headache) and the state at which patients present to the ED Time: 6 monthsDescription: Identification of the ratio of patients with mild or moderate to severe disease
Measure: Identification of the ratio of patients with mild or moderate to severe disease Time: 6 monthsProspective, observational, clinical investigation of PMX cartridge use in COVID 19 patients with septic shock
The proposed hypothesis is that high doses of hydroxychloroquine (HCQ) for at least 2 weeks can be effective antiviral medication both as a treatment in ambulatory patients and prophylaxis/treatment in health care workers because it impairs lysosomal function and reorganizes lipid raft (cholesterol and sphingolipid rich microdomains in the plasma membrane) content in cells, which are both critical determinants of Emerging Viral Disease (EVD) infection. This hypothesis is based on a growing literature linking chloroquine to antiviral activity. It is estimated that enough information exists to launch a clinical trial of hydroxychloroquine for COVID-19.
Description: Rate of hospitalization
Measure: Sub Study 1: Patients Time: 21 daysDescription: Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months
Measure: Sub Study 2: Health Care Workers Time: 2 monthsDescription: any house hold member who has reported symptoms or test positive for COVID 19 during their 14 day active participation
Measure: Sub Study 1: Patients: Rate of secondary infection of co-inhabitants Time: 14 days after enrollment of the householdDescription: Assessment of any medical events that occur during the 14 day active period that is felt to be related to receipt of HCQ
Measure: Sub Study 1: Patients: Adverse Events Time: 14 day active periodDescription: If a test comes back negative, participant would be notified as such and told to destroy their pills as they are withdrawn
Measure: Sub Study 1: Patients: Negative for COVID-19 Time: up to 5 days after enrollingDescription: Any work time missed because the participant experienced COVID-like symptoms during their active 2 month period
Measure: Sub Study 2:Health Care Workers:Number of shifts missed Time: up to ~60 days after enrollmentDescription: Assessment of any medical events that occur during the ~60 day active period that is felt to be related to receipt of HCQ
Measure: Sub Study 2:Health Care Workers:Rate of adverse events Time: up to ~60 days after enrollmentDescription: if the participant gets COVID and has severe symptoms and hospitalized, end point reached if before the end of the 2 month period
Measure: Sub Study 2:Health Care Workers:Rate of hospitalization Time: up to ~60 days after enrollmentThere is an urgent need to evaluate interventions that can prevent the infection with SARS-CoV 2 of healthcare workers at risk. Melatonin is an inexpensive and safe product with protective effect in both bacterial and viral infections likely due to its anti-inflammatory and anti-oxidative effects. This randomized controlled trial seeks to evaluate is efficacy as a prophylaxis in healthcare workers exposed to the virus in their clinical practice.
Description: Number of confirmed (positive CRP) symptomatic infections in each treatment group
Measure: SARS-CoV 2 infection rate Time: up to 12 weeksCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the disease progresses, a series of acute complications tend to develop in multiple organs. Beyond the supportive care, no specific treatment has been established for COVID-19. The effectiveness, both short-term and long-term, of some promising antivirals, such as the hydroxychloroquine combination with azithromycin, needs to be evaluated. This study aims to investigate the predictive role of cardiac biomarkers and pulmonary symptoms for late complications of COVID-19 coronavirus infection on the heart and lung in patients treated with the hydroxychloroquine / azithromycin combination therapy. Thus, COVID-19 coronavirus patients undergoing hydroxychloroquine / azithromycin combination therapy will be compared to patients not undergoing this therapy. The comparison will be made by the analysis of the relationships between (1) levels of ultrasensitive cardiac troponins collected at the beginning of the infection and cardiac magnetic resonance data in the 3rd and 12th months of troponin collection and (2) findings CT scans and the results of the ergospirometers tests performed in those same periods. It is expected to demonstrate that: (1) cardiac troponin and lung tomographic findings can predict late complications of COVID-19 coronavirus infection in the heart and lung, assessed by cardiac magnetic resonance and ergospirometers one year after the beginning of the infection, and (2) hydroxychloroquine / azithromycin combined therapy can abolish the onset of these complications late. Furthermore, the results may point to the need for more rigorous monitoring of cardiologists and pulmonologists of these patients, due to the risk of hemodynamic complications, arrhythmogenic and respiratory.
Description: presence of fibrosis on cardiac resonance and / or decreased functional capacity on ergospirometry
Measure: Fibrosis Time: 12 monthsDescription: Decreased functional capacity on ergospirometers
Measure: Ergospirometers Time: 12 monthesTo test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.
Description: Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs
Measure: Percentage of virus free subjects Time: 7 days after initiation of trialDescription: Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .
Measure: Disease severity Time: 6 daysDescription: Number of subjects in each arm who are hospitalized for Covid 19 infection
Measure: Incidence of hospitalization Time: 14 daysDescription: Number of subjects in each arm who die secondary to Covid-19 infection
Measure: Incidence of Death Time: 70 Days (10 weeks)Description: Number of subjects in each arm who have confirmed Covid-19 infection
Measure: Incidence of confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Number of subjects in each arm who discontinue or withdraw medication use for any reason
Measure: Incidence of all-cause study medication discontinuation or withdrawal Time: 14 daysDescription: Blood tests to determine level of immunity in each subject
Measure: Immunity to Covid-19 Time: 70 days (10 weeks)Chloroquine in COVID-19 treatment
Description: the number of patients with virological cure
Measure: Number of patients with virological cure Time: 6 monthsWe aim to better understand the mode of action of SARS-CoV-2 in the context of its interaction with the host genome through whole genome sequencing.
Description: Clinical associations with human and viral genetics
Measure: Associations with severity and outcomes Time: next 6 monthsAcute kidney injury (AKI) is reported to occur in 0.5-9% of severe acute respiratory distress coronavirus 2-positive patients and AKI has been identified as an independent risk factor for in-hospital mortality. The present study aims to investigate the incidence of renal outcome of in-hospital patients diagnosed with COVID-19.
Description: As determined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria
Measure: Incidence of AKI Time: Within 7 days after admissionDescription: Serial biomarker assessment
Measure: Renal function changes during hospital stay Time: from hospital admission til discharge up to 3 monthsDescription: As determined by KDIGO criteria
Measure: Incidence of chronic kidney disease Time: 3 months post-hospital admissionContext: On March 11, the World Health Organization (WHO) announced the current corona virus disease 2019 (COVID-19) outbreak as a pandemic. The first laboratory-confirmed case of COVID-19 in Austria was announced on February 27, 2020. Since then, the incidence of infection follows a gradual increase. Measurements taken by the Austrian government include travel restrictions, closing of national borders, social distancing, a mandatory use of facemasks in public, and closing of stores and restaurants. The underlying aim of those imposed restrictions is to contain the viral transmission and to slow spreading of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: The aims of this study are to determine i) how many employees in Austrian trauma hospitals and rehabilitation facilities have virus specific IgG and IgM antibodies against SARS-CoV-2, ii) how many are active virus carriers (symptomatic and asymptomatic), iii) how many employees are in their incubation period during the study period, and iv) to calculate the SARS-CoV-2 prevalence together with a specific occupation associated infection risk within the different specifications of health care workers. Study Design: Open uncontrolled observational cross-sectional study. Setting/Participants: A total of 4000 employees in 11 Austrian trauma hospitals and rehabilitation facilities of the Austrian Social Insurance for Occupational Risks (AUVA) will be invited to participate in the study. Study Interventions and Measures: An antibody test for SARS-CoV-2 specific IgG and IgM antibodies, and a RT-PCR test based on oropharyngeal swab samples, as well as laboratory-based antibody tests using ELISA, will be implemented to ensure protection and preservation of health in hospital staff and are not part of the study. The tests will be conducted twice, with approximately two weeks in between testing. The results of the tests will be used for statistical analysis in this study together with a questionnaire including questions related to personal health, traveling activities, living situation, as well as inquiries of symptoms and comorbidities.
Description: To determine how many employees in Austrian trauma hospitals and rehabilitation facilities have already virus specific IgG and IgM antibodies against SARS-CoV-2.
Measure: Antibody status in HCW Time: 4 monthsDescription: To determine how many are actively infected with or without showing symptoms.
Measure: Active virus carriers in HCW Time: 4 monthsDescription: To determine how many employees are in their incubation period during study time.
Measure: Incubation time Time: 4 monthsDescription: To evaluate the "background incidence rate" of COVID-19 to calculate the SARS-CoV-2 prevalence in a defined cohort of the Austrian population.
Measure: Background incidence rate Time: 4 monthsDescription: To calculate a specific occupation associated infection risk within the different specifications of health care workers amongst AUVA employees.
Measure: Occupation associated infection risk Time: 4 monthsCaptopril being an effective drug available in liquid preparation, administration by nebulization could be of interest for maximizing lung action and minimizing systemic side effects. Such a treatment might be used for "Covid-19" patients with pneumonia in order to avoid ARDS.
Description: To assess determine the efficacy of captopril nebulization addition to standard of care compared to standard of care in term of 14-day ventilation free survival
Measure: Efficacy of captopril nebulization addition to standard of care compared to standard of care. Time: 14 DaysRandomized, prospective, controlled open label clinical trial aimed at investigating if the addition of inhaled corticosteroids (budesonide) reduces treatment failure (defined as a composite variable by the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) according to hospital standard of care guidance) at day 15 after initiation of therapeutic intervention.
Description: composite variable that includes the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) at day 15 after initiation of therapeutic intervention
Measure: Proportion of patients in both arms fulfilling the criteria for treatment failure Time: 15 days after treatmentDescription: Yes/no
Measure: ICU admission Time: baseline, day 3, day 7, day 15, day 30Description: yes/no and reason
Measure: ICU refusal Time: baseline, day3, day 7, day 15, day 30Description: infectious cardiovascular and /or metabolic complications as well as variation in the 7 point WHO scale.
Measure: Occurrence of complications Time: baseline, day3, day 7, day 15, day 30Description: U/L
Measure: lactate dehydrogenase (LDH) Time: at baseline, day 3, day 7, day 15, day 30Description: mg/dL
Measure: C Reactive Protein (CRP) Time: at baseline, day 3, day 7, day 15, day 30Description: ng/mL
Measure: ferritin Time: at baseline, day 3, day 7, day 15, day 30Description: ng/mL
Measure: D-dimer Time: at baseline, day 3, day 7, day 15, day 30Description: x10^9/L
Measure: leukocyte counts Time: at baseline, day 3, day 7, day 15, day 30The main purpose of this study is to evaluate the activity, safety and reduction in mortality of two regimens of low dose selinexor (KPT-330) in patients with moderate or severe COVID-19.
The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).
Description: Safety will be defined by the incidence of pre-specified infusion associated adverse events as assessed by treating physician
Measure: Incidence of pre-specified infusion associated adverse events Time: Day 5Description: Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Measure: Incidence of Severe Adverse Events Time: 90 daysDescription: Number of participants that are alive at 90 days post first infusion follow up.
Measure: Survival rate after 90 days post first infusion Time: 90 daysDescription: Number of days participants were off ventilators within up to 28 days of hospitalization
Measure: Ventilator-Free Days Time: 28 days or hospital discharge, whichever is earlierDescription: Measure the fraction of inspired oxygen (FiO2) and its usage within the body during intensive care, measured using fNIRS (Functional Near Infrared Spectroscopy).
Measure: Change in Oxygenation Index (OI) Time: 28 daysDescription: Measuring respiratory mechanics in ventilated patients [plateau pressure (Pplat)-positive end-expiratory pressure]
Measure: Plat-PEEP Time: 28 daysDescription: The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure)
Measure: Sequential Organ Failure Assessment (SOFA) Scores Time: 28 daysDescription: The SIT is a self-administered 40-item test involving microencapsulated (scratch-and-sniff) odors with a forced-choice design. The test has a total score ranging from 0-40 Follows scoring key for evaluation. The higher score indicates better outcome.
Measure: Small Identification Test (SIT) scores Time: At baseline, day 18 and day 28.Description: As assessed via serum blood samples.
Measure: Troponin I levels Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: C-Reactive Protein levels Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: Arachidonic Acid (AA)/Eicosapentaenoic Acid (EPA) Ratio Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: D-dimer levels Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: 25-Hydroxy Vitamin D levels Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: Alloantibodies levels Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: Blood white cell count Time: Baseline, 28 daysDescription: As assessed via serum blood samples.
Measure: Platelets count Time: Baseline, 28 daysThis trial will estimate the efficacy and tolerance of several experimental treatments to prevent hospitalization or death in outpatients aged 65 years or above with Symptomatic SARS-CoV-2 Infection (COVID-19).
Description: Proportion of participants with an occurrence of death
Measure: Death Time: From inclusion (day0) to day 14Description: Proportion of deaths, overall and by cause, in each group
Measure: Death and causes of death Time: From inclusion (day0) to day 28Description: Evolution of Haematological markers in each group : Complete Blood Count, prothrombin level, INR
Measure: Haematological markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of Biochemical markers in each group : ferritin, serum creatinine, urea, sodium, potassium, chlorine, calcium, magnesium, albumin, bicarbonates / tCO2, LDH, CPK, ASAT, ALAT, uricemia
Measure: Biochemical markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of Inflammatory markers in each group : PCT, CRP
Measure: Inflammatory markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of immunological markers in each group : B ans T Cells phenotypic profiles
Measure: Immunological markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Number and proportion of grade 1,2,3,4 adverse events in each group
Measure: Adverse events Time: from inclusion (day 0) to day 14Description: Number and proportion of grade 1,2,3,4 adverse events in each group
Measure: Adverse reactions Time: from inclusion (day 0) to day 14Description: Plasma concentration of the study drugs at D7
Measure: Plasma concentration Time: day 7Description: Acceptability of the treatment by participant will be assessed with an interview
Measure: Acceptability of the treatment Time: from inclusion (day 0) to day 10COVID-19 disease has become a very serious global health problem. Treatments for severe forms are urgently needed to lower mortality. Any procedure that improves these forms should be considered, especially those devoid of serious side effects.There is not enough published information on the use of allogeneic convalescent plasma (ACP) in the treatment of severe forms of COVID-19. The use of ACP can be combined with other treatments and has very few adverse effects. It takes 10-14 days for SARS-CoV2-infected patients to produce virus-neutralizing antibodies: within that time they can develop serious complications and die. Injecting PAC into patients with severe forms of COVID-19 shortens the period of risk while the patient produces the antibodies.
Description: PaO2/FiO2 relation
Measure: Lung injury Time: 7 daysDescription: Patients survival after therapy
Measure: Overall survival Time: 15-30 daysDescription: Determine the incidence of side effects from plasma administration
Measure: Adverse reactions to plasma Time: 7 daysThe present Diagnostic Accuracy study aims at experimentally validating the use of a rapid salivary test to detect SARS-CoV-2 infection in both symptomatic and asymptomatic individuals as a preliminary approach to a mass screening program. The study is based on a consecutive recruitment of both patients showing symptoms probably associated with COVID-19 (i.e., cough, dyspnea, fever) and asymptomatic patients with a low risk phenotype. The expected number of recruited individuals is 100. The experimental test is a prototype of salivary test based on the Lateral Flow Immunoassay technique and is able to detect the presence of SARS-CoV-2 in saliva, especially the Spike protein (S). The comparison is represented by the nasopharyngeal swab, the gold standard of COVID-19 diagnosis. Patients will undergo both salivary immunoassay and nasopharyngeal swab, thus the outcome assessors are blinded, since the results of the rRT-PCR analysis require at least 6 hours before being available. The main outcomes are sensibility and specificity of the rapid salivary test, when compared with the gold standard (nasopharyngeal swab).
Description: TP/TP+FN (TP= True Positive; FN = False Negative)
Measure: Sensibility Time: Salivary test will be interpreted after 10 minutes; the nasopharyngeal swab after 6 hours; sensitivity recorded through study completion, an average of 2 months.Description: TN/TN+FP (TN= True Negative; FP= False Positive)
Measure: Specificity Time: Salivary test will be interpreted after 10 minutes; the nasopharyngeal swab after 6 hours; specificity recorded through study completion, an average of 2 months.In the SAVE study patients with lower respiratory tract infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at high risk for progression to serious respiratory failure will be detected using the suPAR biomarker. They will begin early treatment with anakinra in the effort to prevent progression in serious respiratory failure. Also due to the potential co-existing immunodysfunction in the context of SARS-CoV-2 infection patients will also receive trimethoprim/sulfamethoxazole as part of chemoprophylaxis.
Description: The primary study endpoint is the ratio of patients who will not develop serious respiratory failure SRF until day 14. Patients dying before study visit of day 14 are considered non-achieving the primary endpoint.
Measure: The ratio of patients who will not develop serious respiratory failure (SRF) Time: Visit study day 14Description: Evaluation of clinical data (pO2/FiO2 and need of mechanical ventilation) between baseline and study visit day 14 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of the rate of patients who will not develop serious respiratory failure (SRF) until day 14 with historical comparators from Hellenic Sepsis Study Group Database Time: Visit study day 14Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 7
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 14
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 7 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of SOFA score in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 14 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of Sequential organ failure assessment (SOFA) score in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of cytokine stimulation from peripheral blood mononuclear cells of enrolled subjects will be compared between days 1 and 7
Measure: Change of cytokine production between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of plasma inflammatory mediators measured levels will be compared between days 1 and 7
Measure: Change of plasma inflammatory mediators levels between days 1 and 7 Time: Visit study day 1, visit study day 7The global pandemic COVID-19 has overwhelmed the medical capacity to accommodate a large surge of patients with acute respiratory distress syndrome (ARDS). In the United States, the number of cases of COVID-19 ARDS is projected to exceed the number of available ventilators. Reports from China and Italy indicate that 22-64% of critically ill COVID-19 patients with ARDS will die. ARDS currently has no evidence-based treatments other than low tidal ventilation to limit mechanical stress on the lung and prone positioning. A new therapeutic approach capable of rapidly treating and attenuating ARDS secondary to COVID-19 is urgently needed. The dominant pathologic feature of viral-induced ARDS is fibrin accumulation in the microvasculature and airspaces. Substantial preclinical work suggests antifibrinolytic therapy attenuates infection provoked ARDS. In 2001, a phase I trial 7 demonstrated the urokinase and streptokinase were effective in patients with terminal ARDS, markedly improving oxygen delivery and reducing an expected mortality in that specific patient cohort from 100% to 70%. A more contemporary approach to thrombolytic therapy is tissue plasminogen activator (tPA) due to its higher efficacy of clot lysis with comparable bleeding risk 8. We therefore propose a phase IIa clinical trial with two intravenous (IV) tPA treatment arms and a control arm to test the efficacy and safety of IV tPA in improving respiratory function and oxygenation, and consequently, successful extubation, duration of mechanical ventilation and survival.
Description: Ideally, the PaO2/FiO2 will be measured with the patient in the same prone/supine position as in baseline, as change in positions may artificially reduce the improvement attributable to the study drug. However, given the pragmatic nature of the trial, the prone/supine position will be determined by the attending physician, in which case, we will use as an outcome the PaO2/FiO2 closest to the 48 hours obtained prior to the change in position as the outcome.
Measure: PaO2/FiO2 improvement from pre-to-post intervention Time: at 48 hours post randomizationDescription: Achievement of PaO2/FiO2 ≥ 200 or 50% increase in PaO2/FiO2 (whatever is lower)
Measure: Achievement of PaO2/FiO2 ≥ 200 or 50% increase in PaO2/FiO2 Time: at 48 hours post randomizationDescription: This score is based on seven clinical features (respiration rate, hypercapnic respiratory failure, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness) and determines the degree of illness of a patient and prompts critical care intervention.
Measure: National Early Warning Score 2 (NEWS2) Time: at 48 hours post randomizationDescription: The ordinal scale is an assessment of the clinical status as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. (combined items 7 and 8 as our study is limited to hospital).
Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale Time: at 48 hours post randomizationDescription: 48 hour mortality for hospitalized patients
Measure: 48 hour in-hospital mortality Time: at 48 hours post randomizationDescription: 14 days mortality for hospitalized patients
Measure: 14 days in-hospital mortality Time: 14 days post randomizationDescription: 28 days mortality for hospitalized patients
Measure: 28 days in-hospital mortality Time: 28 days post randomizationDescription: ICU-free days will be calculated based on (28 - number of days spent in the ICU) formula
Measure: ICU-free days Time: 28 days of hospital stay or until hospital discharge (whichever comes first)Description: In-hospital coagulation-related events include bleeding, stroke, myocardial infarction and venous thromboembolism (VTE). In-hospital coagulation-related event-free (arterial and venous) days will be calculated based on (28 - number of days without coagulation-related event) formula.
Measure: In-hospital coagulation-related event-free (arterial and venous) days Time: 28 days of hospital stay or until hospital discharge (whichever comes first)Description: Ventilator-free days will be calculated based on (28 - number of days on mechanical ventilation) formula.
Measure: Ventilator-free days Time: 28 days of hospital stay or until hospital discharge (whichever comes first)Description: Calculated for patients who was on a mechanical ventilation any period of time during hospitalization. The extubation will be considered successful if no re-intubation occurred for more than 3 days have passed after the initial extubation.
Measure: Successful extubation Time: Day 4 after initial extubationDescription: Calculated for patients who was on paralytics at the time of randomization. The weaning will be considered successful if no paralytics were used for more than 3 days have passed after termination of paralytics.
Measure: Successful weaning from paralysis Time: Day 4 after initial termination of paralyticsDescription: Is counted for the patients who was alive at the time of discharge.
Measure: Survival to discharge Time: 28 days of hospital stay or until hospital discharge (whichever comes first)Previous research has shown that high dose intravenous vitamin C (HDIVC) may benefit patients with sepsis, acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS). However, it is not known if early administration of HDIVC could prevent progression to ARDS. We hypothesize that HDIVC is safe and tolerable in Coronavirus disease 2019 (COVID-19) subjects given early or late in the disease course and may reduce the risk of respiratory failure requiring mechanical ventilation and development of ARDS along with reductions in supplemental oxygen demand and inflammatory markers.
Description: Occurrence of adverse events during study drug infusion
Measure: Incidence of adverse events Time: Days 1-4Description: Occurrence of serious adverse events during study drug infusion
Measure: Incidence of serious adverse reactions Time: Days 1-4Description: Occurrence of adverse reactions during study drug infusion
Measure: Incidence of adverse reactions Time: Days 1-4Description: Documented days free off mechanical ventilation the first 28 days post enrollment
Measure: Ventilator-free days Time: Days 1-28Description: Documented days free of ICU admission the first 28 days post enrollment
Measure: ICU-free days Time: Days 1-28Description: Documented days free of hospital admission the first 28 days post enrollment
Measure: Hospital-free days Time: Days 1-28Description: Incidence of mortality at 28 days by all causes
Measure: All-cause mortality Time: Days 1-28Description: SpO2 (% peripheral oxygenation saturation) will be divided by fraction of inspired oxygen (FiO2) at start of study infusion and compared with S/F ratio at end of study infusion
Measure: Change in S/F ratio during HDIVC infusion Time: Days 1-4Description: The difference in serum CRP from start of HDIVC infusion to day 7 will be reported in mg/dL
Measure: C-reactive protein (CRP) Time: Days 1-7Description: The difference in LDH from start of HDIVC infusion to day 7 will be reported in IU/L
Measure: Lactate dehydrogenase (LDH) Time: Days 1-7Description: The difference in D-dimer from start of HDIVC infusion to day 7 will be reported in ug/mL
Measure: D-dimer Time: Days 1-7Description: The difference in lymphocyte count from start of HDIVC infusion to day 7 will be reported in 10e3/uL
Measure: Lymphocyte count Time: Days 1-7Description: The NLR will be calculated by dividing the absolute neutrophil count (10e3/uL) over the absolute lymphocyte count (10e3/uL) and ratio compared with Day 1 versus Day 7
Measure: Neutrophil to Lymphocyte ratio (NLR) Time: Days 1-7Description: The difference in serum ferritin will be calculated from the start of HDIVC infusion to day 7 and reported as ng/mL
Measure: Serum Ferritin Time: Days 1-7The study objective is to investigate the diagnostic value and consistency of chest CT as compared with comparison to RT-PCR assay in COVID-19 in patients which were stratified for hospital admission.
Description: Positive likelihood ratio (LR+) Negative likelihood ratio (LR-)
Measure: Sensitivity and specificity of chest CT in detecting pneumonia in unspecific symptomatic patients who are to be admitted to hospital and who are rt-PCR negative for SARS-CoV-2. Time: At hospital admissionDescription: Sensitivity and specificity of chest CT in detecting pneumonia in unspecific symptomatic patients with pulmonary comorbidities who are to be admitted to hospital and who are rt-PCR negative for SARS-CoV-2.
Measure: Sensitivity and specificity of chest CT in patients with pulmonary comorbidities Time: At hospital admissionDescription: Sensitivity and specificity of chest CT in detecting pneumonia in unspecific symptomatic patients with cardiovascular comorbidities who are to be admitted to hospital and who are rt-PCR negative for SARS-CoV-2.
Measure: Sensitivity and specificity of chest CT in patients with cardiovascular comorbidities Time: At hospital admissionDescription: Sensitivity and specificity of chest CT in detecting pneumonia in unspecific symptomatic patients with malignancy who are to be admitted to hospital and who are rt-PCR negative for infection with SARS-CoV-2.
Measure: Sensitivity and specificity of chest CT in patients with malignancy Time: At hospital admissionDescription: Sensitivity and specificity of chest CT in detecting pneumonia in unspecific symptomatic patients with immunodeficiency who are to be admitted to hospital and who are rt-PCR negative for SARS-CoV-2.
Measure: Sensitivity and specificity of chest CT in patients with immunodeficiency Time: At hospital admissionDescription: Predictive value of chest CT
Measure: Predictive value of specific chest CT findings for detection of SARS-CoV-2 Time: At hospital admissionThe search for novel therapies to address the ongoing coronavirus (COVID-19) pandemic is ongoing. No proven therapies have been identified to prevent progression of the virus. Preliminary data suggest that inhaled nitric oxide (iNO) could have benefit in preventing viral progression and reducing reliance on supplemental oxygen and ventilator support. Expanded access allows for iNO to be delivered via the portable INOpulse delivery system for the treatment of COVID-19.
For limiting COVID-19 spreading, the World Health Organisation (WHO) recommended worldwide confinement on 2010. In France, unessential institutions were closed on March 14th and population confinement was decided on March 17th. Quarantine and/or confinement could lead to psychological effects such as confusion, suicide ideation, post-traumatic stress symptoms or anger COVID-19 outbreak highlighted a considerable proportion of health care workers (HCW) with depression, insomnia, anxiety and distress symptoms. In front line, facing the virus with the fear of contracting it and contaminate their closest. During previous outbreaks (H1N1, SARS), HCWs have been shown to experience such negative psychological effects of confinement as well as work avoidance behaviour and physical interaction reduction with infected patients (4-7). In France, Covid 19 outbeak led to increase ICU bed capacity with a full reorganization of the human resources. Some caregivers were reassigned to newly setup units admitting or not Covid-19 patients. In the same time, non-caregivers were also encouraged to work at home whenever possible. Thus, every hospital staff member's private and professional life could be altered by the Covid-19 outbreak. As all these changes in the daily life could induce psychological disturbances, the present study was aimed at assessing the acute anxiety level (main objective) of the staff in our Tertiary University Hospital, (6300 employees). Secondarily, the self-reported insomnia, pain, catastrophism and work avoidance behaviour levels were assessed
Description: Mesured by STAY Scale
Measure: Anxiety Time: 15 to 45 days after the beginning of the outbreakDescription: Participant suffering of Insomnia
Measure: Insomnia Time: 15 to 45 days after the beginning of the outbreakDescription: Participant suffering of catastrophism
Measure: Catastrophism Time: 15 to 45 days after the beginning of the outbreakIn early December 2019, cases of pneumonia of unknown origin were identified in Wuhan, China. The causative virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of international concern. According to the World Health Organization (WHO), the management of COVID-19 has focused primarily on infection prevention, detection and patient monitoring. However, there is no vaccine or specific treatment for SARS-CoV-2 due to the lack of evidence. Treatment options currently include broad-spectrum antiviral drugs but the efficacy and safety of these drugs is still unknown. Convalescent plasma has previously been used to treat various outbreaks of other respiratory infections; however, it has not been shown to be effective in all the diseases studied. Therefore, clinical trials are required to demonstrate its safety and efficacy in patients with VIDOC-19. The present work seeks to determine the mortality from any cause up to 14 days after plasma randomization of patients cured of COVID-19 compared to the Best Available Therapy in subjects with SARS-CoV-2 pneumonia. This is a 2:1 randomized, double-blind, single-center, phase 2, controlled clinical trial (plasma: best available therapy) for the treatment of SARS-CoV-2 pneumonia.
Description: any cause mortality during the first 14 days of treatment
Measure: Early all-cause mortality Time: 14 daysDescription: (48-hour sampling interval from day 3 of hospitalization to two consecutive negatives).
Measure: Time in days for SARS-CoV-2 RT-PCR negatives Time: 90 daysDescription: In subjects of both arms at day 0, 3, 7, 14 and 90.
Measure: The serum anti-SARS-CoV-2 antibody titres Time: 90 daysDescription: Comparison of anti-SARS-CoV-2 antibody titers
Measure: Detection of serum antibodies Time: days 0, 3, 7, 14 and 90.The consensus therapeutic strategy implies that COVID patients with acute lung injury due to coronavirus are routinely placed in prone position in an attempt to improve oxygenation by increasing ventilation homogeneity. The purpose of the study is quantify with the electrical impedance tomography (EIT) the changes in the ventilation and aeration in the dorsal regions of the lung when the patient is placed in prone position.
Description: Change in the ratio of tidal electrical impedance variation in the dorsal and total lung areas
Measure: Tidal electrical Impedance Time: One hour before turning to prone or supine positioningDescription: Changes in intrapulmonary shunt fraction
Measure: Intrapulmonary shunt Time: One hour before turning to prone or supine positioningDescription: Changes in the phase three slope of the volumetric capnogram
Measure: Volumetric capnography Time: One hour before turning to prone or supine positioningThis randomized blinded phase 2 trial will assess the efficacy and safety of Anti-SARS-CoV-2 convalescent plasma among adults with severe COVID-19. Adults ≥18 years of age may participate. A total of 105 eligible subjects will be randomized in a 2:1 ratio to receive either high-titer anti-SARS-CoV-2 plasma or non-convalescent fresh frozen plasma (control plasma).
Description: The efficacy of treatment will be determined by determining the time-to-clinical improvement, defined as the time from randomization to either an improvement of one point on a seven-category ordinal scale or alive discharge from the hospital, whichever comes first.
Measure: Time to Improvement Time: Up to 28 daysDescription: Compare the rates of SARS-CoV-2 PCR positivity (RT PCR) amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Measure: Rate of SARS-CoV-2 PCR Positivity Time: Up to 14 daysDescription: Compare the duration of SARS-CoV-2 PCR positivity (RT PCR) amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Measure: Duration of SARS-CoV-2 PCR Positivity Time: Up to 14 daysDescription: Compare duration of need for supplemental oxygen and/or mechanical ventilation amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Measure: Duration of Need for Supplemental Oxygen Time: Up to 28 daysDescription: Compare duration of hospitalization amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Measure: Duration of Hospitalization Time: Up to 28 daysDescription: Compare in-hospital and 28-day mortality amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Measure: In-hospital 28-day Mortality Rate Time: Up to 28 daysThis study seeks to determine whether the virus which causes COVID-19, SARS-CoV-2, is shed in the stools of patients who are infected.
Description: Relative abundance of bacterial classes within taxonomic phyla and, more broadly, within their domain will be analyzed by sequencing the gut microbiome. These data will then be categorized among specific gastrointestinal disease types.
Measure: Correlation of Microbiome to Disease via Relative Abundance Found in Microbiome Sequencing Time: One yearDescription: To validate the methods used to sequence samples
Measure: Validation of Sequencing Methods Time: One yearWe plan to generate a database of viral RNA sequences for SARS-CoV-2 within the Wessex region. Such whole genome data can be used to monitor mutation rates in real time and, through comparison with global databases of SARS-CoV-2 genome sequences, can be used to map transmission of the virus
Description: Generated using Nanopore-based whole genome sequencing techniques
Measure: To produce whole genome sequences for the SARS-CoV-2 virus from viral RNA samples Time: 2 yearsDescription: Identify mutations and viral strains prevalent within the Wessex region
Measure: To develop a phylogenetic map of the SARS-CoV-2 virus Time: 2 yearsThis treatment protocol is designed to provide a treatment option for patients diagnosed with severe or life-threatening COVID-19 or judged by the subinvestigator (treating physician) to be at high risk of progressing to severe or life threatening disease
The investigators hypothesize that those with respiratory failure due to COVID-19 will have different burdens of mental and physical disability than those with respiratory failure who do not have COVID-19. Detecting these potential differences will lay an important foundation for treating long term sequelae of respiratory failure in these two cohorts.
Description: SF-36 score
Measure: Quality of Life score Time: up to 12 months after dischargeDescription: Montreal Cognitive Assessment (MoCA) score
Measure: cognitive dysfunction Time: up to 12 months after dischargeDescription: (FSS-ICU)
Measure: Functional Status Score Time: up to 12 months after dischargeDescription: MRC neuromuscular Assessment
Measure: Physical Disability Time: up to 12 months after dischargeDescription: Impact Event Score
Measure: Psychological Sequelae Time: up to 12 months after dischargeDescription: hospital anxiety and depression scale
Measure: hospital anxiety and depression Time: up to 12 months after dischargeDescription: including ventilator associated pneumonia, GI hemorrhage, Deep Vein Thrombosis (DVT) /Pulmonary Embolus (PE), sacral decubitus ulcer, delirium, ICU acquired weakness
Measure: ICU related complications Time: hospitalization up to 6 weeksDescription: measure the location (home, rehabilitation center, nursing home
Measure: hospital discharge location Time: hospital discharge up to 6 weeksDescription: number of days admitted to the ICU
Measure: lCU length of stay Time: hospitalization up to 6 weeksDescription: number of days admitted to the hospital
Measure: hospital length of stay Time: hospitalization up to 6 weeksThe purpose of this study is to determine whether the virus SARS-CoV-2, responsible for the disease COVID-19, is present in the abdominal cavity during emergency laparoscopic exploration in confirmed or suspected COVID-19 patients.
Description: Assessment of the presence of the SARS-COV-2 virus by RT-PCR in the peritoneum at the end of the surgical procedure with exsufflation (T4) in COVID-19 patients
Measure: Assessment of the presence of the SARS-COV-2 virus at T4 Time: After surgery, an average of half a dayDescription: Assessment of the presence of the SARS-COV-2 virus by RT-PCR immediately after creation of the pneumoperitoneum just before intraperitoneal surgical exploration (T1) in COVID-19 patients
Measure: Assessment of the presence of the SARS-COV-2 virus at T1 Time: After surgery, an average of half a dayDescription: Assessment of the presence of the SARS-COV-2 virus by RT-PCR in the peritoneal effusion found during surgical exploration (T2) or in the peritoneal lavage fluid at the end of the surgical procedure before exsufflation (T4) in COVID-19 patients
Measure: Assessment of the presence of the SARS-COV-2 virus in the peritoneal effusion at T2 or T4 Time: After surgery, an average of half a dayDescription: Assessment of the presence of the SARS-COV-2 virus by RT-PCR in the pneumoperitoneum during intraperitoneal surgical dissection (T2) with straight blunt/sharp or any kind of energy devices in COVID-19 patients
Measure: Assessment of the presence of the SARS-COV-2 virus at T3 Time: After surgery, an average of half a dayDescription: Assessment of the presence of the SARS-COV-2 virus by RT-PCR in the bile at the end of the intervention after specimen extraction (T5), in case a cholecystectomy is performed in COVID-19 patients
Measure: Assessment of the presence of the SARS-COV-2 virus at T5 Time: After surgery, an average of half a dayThe Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) has been identified in Wuhan, China, which causes severe pulmonary complications and flu syndrome, which has spread rapidly to all continents. Approximately 25% of hospitalized patients require treatment in intensive care units and 10% require mechanical ventilation. The diagnosis is made by the molecular polymerase chain reaction test. However, diagnostic tests are limited. The clinical care of the patient with COVID-19 is similar to that of patients with severe infectious respiratory complications, consisting of support and oxygen supplementation. Several medications have been tested as remdesivir, a pro-drug nucleoside, which acts by inhibiting viral RNA transcription, although a recently published study has shown no benefit. China recently approved the use of favipiravir, an antiviral used for influenza, as an experimental therapy for COVID-19. Hydroxychloroquine is a drug with great potential treatment, as it can inhibit the pH-dependent steps of replication of various viruses, with a potent effect on SARS-CoV infection and spread. In this way, the present study will evaluate the safety and efficacy of the hydroxychloroquine in patients with symptomatic SARS-Cov2.
Description: The individual response rate regarding the World Health Organization Ordinal Scale assessment from basal to 14th Day.
Measure: Individual response rate Time: 14 days after randomizationDescription: All-cause mortality rates at Day 28th after randomization
Measure: All-cause mortality Time: 28 days after randomizationDescription: Number of days that the patient was on mechanical ventilation which was under ventilation from basal line
Measure: Duration of mechanical ventilation Time: baselineDescription: Proportion of patients who do not receive mechanical ventilation at the beginning of the study and then needed mechanical ventilation during hospitalization.
Measure: Proportion of patients which needed mechanical ventilation during study Time: hospitalization within 28 daysDescription: The ordinal scale is an assessment of the clinical status at the first clinical evaluation in a clinical study. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: World Health Organization (WHO) Ordinal scale Time: 28 days after inclusion and compared to baselineDescription: Length of hospital stay in days for hospitalization
Measure: Duration of hospitalization Time: hospitalization within 28 daysDescription: Rates of drug discontinuation in all causes under study
Measure: Rates of drug discontinuation Time: hospitalization within 28 daysDescription: Rates of serious adverse events
Measure: Rates of serious adverse events Time: Day 14thBackground: There are no proven therapies for COVID-19 infection. COVID-19 infects the respiratory epithelium of the lower airways, causing widespread damage via cytopathic effects, resulting in severe inflammation and Pneumonitis. High local and circulating levels of cytokines, or cytokine storm, can lead to capillary leak syndrome, progressive lung injury, respiratory failure and acute respiratory distress syndrome (ARDS). Methods: This is a pilot randomized, controlled, uni-center study testing safety and efficacy of cytokine filtration on patients with severe ARDS. Eligible patients will be randomized to 72 hours filtration or no filtration on top of the standard treatment for ARDS. Indications for randomization are patients with moderate or severe ARDS with need of ventilation support (either invasive or non-invasive), with inflammatory markers. The primary outcome will be days on mechanical ventilation (MV) support. Secondary outcomes are 30-day mortality, ICU days, need for extracorporeal membrane oxygenation (ECMO) support, duration of renal replacement therapy (RRT) and catecholamine therapies, hospital length of stay, multi-organ failure. All analysis will be done according to the intention to treat principle.
Description: Number of ventilator-free days (VFDs) at day 28 (defined as days being alive and free from mechanical ventilation at day 28 after enrollment. For patients ventilated 28 days or longer and for ventilated subjects who die, VFD is 0
Measure: Mechanical ventilation-free days Time: up to 28daysThis is a multicenter; double blind randomized controlled study investigating the role of remote intercessory multi-denominational prayer on clinical outcomes in COVID-19 + patients in the intensive care unit. All patients enrolled will be randomized to use of prayer vs. no prayer in a 1:1 ratio. Each patient randomized to the prayer arm will receive a "universal" prayer offered by 5 religious denominations (Christianity, Hinduism, Islam, Judaism and Buddhism) in addition to standard of care. Whereas the patients randomized to the control arm will receive standard of care outlined by their medical teams. During ICU stay, patients will have serial assessment of multi-organ function and APACHE-II/SOFA scores serial evaluation performed on a daily basis until discharge. Data assessed include those listed below.
Description: This study will measure the difference in mortality of COVID-19 patients who are admitted to ICU - given prayer vs no prayer as an adjunct to standard therapy.
Measure: Impact of multi-denominational prayer on clinical outcomes of critically ill COVID-19 patients in the Intensive Care Unit on mortality. Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysDescription: APACHE II uses 0-71 scale, the higher the score the higher the risk for mortality.
Measure: Difference in patient outcomes - Acute Physiology and Chronic Health Enquiry. APACHE II score. Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 days.Description: The higher the SOFA score the increased likelihood of organ failure.
Measure: Difference in patient outcomes - Sequential Organ Failure Assessment - SOFA Score Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysDescription: A prolonged length of time in ICU increases mortality.
Measure: Difference in patient outcomes - Length of stay in ICU. Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysDescription: A prolonged length of time with ventilator support increases mortality.
Measure: Difference in patient outcomes - Length of ventilator support Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysDescription: A prolonged length of time with vasopressor support increases recovery time.
Measure: Difference in patient outcomes - length of vasopressor support Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysIt is an observational, cohort, retrospective, monocentric, non-profit study. The primary objective is to evaluate the efficacy and safety of ruxolitinib in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours.
Description: Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours
Measure: Number of patients who avoid mechanical assisted ventilation in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 Time: 15 daysDescription: ABG (arterial Blood Gas): pH as SI Unit, every 12 hours and in any case in the presence of significant clinical variations.
Measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pH Time: 15 daysDescription: ABG (arterial Blood Gas): pO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations.
Measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pO2 Time: 15 daysDescription: ABG (arterial Blood Gas): pCO2 in mm Hg, every 12 hours and in any case in the presence of significant clinical variations.
Measure: Improvement of respiratory performance - Arterial Blood Gas Analisys - pCO2 Time: 15 daysDescription: PaO2 / FiO2, SatO2 ratio. Vital parameters and respiratory function every 12 hours and in any case in the presence of significant clinical variations.
Measure: Improvement of respiratory performance - ratio values Time: 15 daysDescription: every 24 hours D-Dimer value in mgr/ml
Measure: Evaluation of known adverse events related to the use of the drug - D-Dimer Time: 15 daysDescription: every 24 hours fibrinogen value in mg/dl
Measure: Evaluation of known adverse events related to the use of the drug - fibrinogen Time: 15 daysDescription: every 24 hours transaminases value in U/L
Measure: Evaluation of known adverse events related to the use of the drug - transaminases Time: 15 daysDescription: every 24 hours aPTT value in seconds
Measure: Evaluation of known adverse events related to the use of the drug - aPTT Time: 15 daysDescription: every 24 hours INR value in %
Measure: Evaluation of known adverse events related to the use of the drug - INR Time: 15 daysDescription: every 24 hours glycemia value in mg/dl
Measure: Evaluation of known adverse events related to the use of the drug - glycemia Time: 15 daysDescription: every 24 hours creatinine serum value in mg/dl
Measure: Evaluation of known adverse events related to the use of the drug - creatinine Time: 15 daysDescription: Total leucocyte as CBC x10e)/L
Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes count Time: 15 daysDescription: formula % on total leucocyte
Measure: Evaluation of known adverse events related to the use of the drug - Leucocytes formula Time: 15 daysDescription: Thoracic imaging, every 48 h: presence, extension and dimension on lung thickening - Chest CT at start and end of treatment, Time elapsed between the onset of clinical symptoms and hospitalization.
Measure: Evaluation of the epidemiological parameters: Chest CT Time: 15 daysDescription: Thoracic imaging: every day: presence and number of line B every 48 hours.Time elapsed between the onset of clinical symptoms and hospitalization.
Measure: Evaluation of the epidemiological parameters: Eco Chest Time: 15 daysDescription: Thoracic imaging: presence, extension and dimension on lung thickening - Chest X-ray, Time elapsed between the onset of clinical symptoms and hospitalization.
Measure: Evaluation of the epidemiological parameters: CHEST X-ray Time: 15 daysDescription: Monitoring of serum cytokines (IL-6 in pgr/dL, TNF in pgr/dL) every 48 h
Measure: Monitoring of Serum levels of cytokines before and every 48 h from start to to end of treatment Time: 15 daysDescription: Number of AE grade 1 to 4
Measure: Monitoring incidence of treatment Emergent Adverse Events of ruxolitinib therapy Time: 15 daysThis is a prospective adaptive cohort study of St. Jude employees to determine the rate of SARS-CoV-2 infections that are asymptomatic and to evaluate immunological responses to SARS-CoV-2 infection. Primary Objectives - To estimate the proportion of asymptomatic infection with SARS-CoV-2 infection in a population of SARS-CoV-2-naïve adult St. Jude employees - To comprehensively map CD4 and CD8 T cell epitopes and response magnitudes to SARS-CoV-2 infection in a population of SARS-CoV-2-naïve adult St. Jude employees who acquire SARS-CoV-2 infection Secondary Objectives - To establish seroprevalence of SARS-CoV-2-specific antibodies at baseline, and identify the rate of seroconversion to SARS-CoV-2 in a population of presumably naïve adult St. Jude employees - To identify features of T cell responses at baseline and during SARS-CoV-2 infection that are associated with protection against symptomatic or severe COVID-19 disease in a population of adult St. Jude employees Exploratory Objectives - To establish additional immunological features including host immune or receptor polymorphisms associated with response to SARS-CoV-2 infection - To explore SARS-CoV-2 diversity and specific features in a circumscribed population - To describe the presence, characteristics, and proportion of short-term re-infection - To determine if an association between SARS-CoV-2 viral load in nasal swab specimens and COVID-19 symptoms can be identified in a population of adult St. Jude employees who acquire SARS-CoV-2
Description: The proportion of participants who test positive for SARS-CoV-2 infection but remain asymptomatic.
Measure: Proportion of asymptomatic subjects Time: 1 year from enrollmentDescription: A list of CD4 and CD8 cell epitopes with a magnitude change from baseline that is at least twice the standard deviation of the baseline.
Measure: Positive CD4 and CD8 cell epitope positive response Time: at enrollment, 3 months, 6 months, 9 months and 1 yearDescription: The proportion of participants at each time point who have detectable antibodies that recognize SARS-COV-2.
Measure: Proportion of seroprevalence Time: Baseline, 3 months, 6 months, 9 months and 1 yearDescription: For CD8s, T cell responses will be categorized as cytolytic, cytokine producing, or exhausted. For CD4s they will be grouped as Th1, Th2, Tfh, or Th17. Percentages of cells in each category will be summarized at baseline and during SARS-CoV-2 infection.
Measure: T-cell response Time: Baseline, 3 months, 6 months, 9months and 1 yearACCESS enables individuals to contribute to critical research, via an iOS and Android smartphone mobile application. ACCESS combines patient reported outcomes, data from wearable devices and real-world data (such as claims, EHRs, etc), with an opt-in to participate in current and future studies for diagnostics, treatments and vaccines. The data that people share can be quickly and anonymously matched to research studies, providing researchers with a foundational framework for dynamic research at scale and participants a way to be personally matched and prescreened for future research.
Description: To use multifaceted participant data consisting of participant reported outcomes, environmental surface and presence or absence of COVID-19 based on testing results, prescription medications (including off-label use), claims, lab, and medical record data to develop population-based models of disease risk, short and long-term outcomes, and efficacy of interventions and prevention measures.
Measure: Development of population-based models of disease risk Time: Up to 10 yearsDescription: To leverage geolocation and lab results to provide population-level real-time data regarding disease burden at the community, state and national levels.
Measure: Relation between disease burden and geolocation Time: Up to 10 yearsDescription: To specifically identify medications and regimens that address disease symptoms
Measure: Effect of medications on symptoms of COVID19 Time: Up to 10 yearsDescription: To specifically identify medications and regimens that treat and reduce disease severity.
Measure: Effect of medications on disease severity of COVID19 Time: Up to 10 yearsDescription: To identify regional variations in disease incidence and outcomes.
Measure: Rate of COVID19 infection and disease outcomes Time: Up to 10 yearsDescription: To understand long-term outcomes such as risk of pulmonary and cardiovascular disease complications.
Measure: Effect of COVID19 on health outcomes Time: Up to 10 yearsDescription: To conduct long-term follow up of individuals who tested positive for COVID-19 compared to demographically matched individuals that did not.
Measure: Long-term follow up and recontact Time: Up to 10 yearsThe most prevalent complication of COVID-19 infection is respiratory failure from severe acute respiratory syndrome (SARS), the leading cause of mortality. There is increasing indication that the decompensation in severe COVD-19 infection may be due to a cytokine storm syndrome. This hyperinflammatory syndrome results in a fulminant and fatal hypercytokinemia and multiorgan failure. Approximately 15% of patients with COVID-19 infection are hospitalized and 20-30% of these hospitalized patients require ICU care and/or mechanical ventilation. Overall mortality in hospitalized patients is approximately 20-25%. There is significant interest in therapies that can be given upstream to reduce the rate of mechanical ventilation and thus mortality. We hypothesize that treatment with colchicine in COVID-19 moderate-severe patients may decrease the risk of progression into ARDS requiring increased oxygen requirements, mechanical ventilation, and mortality.
This a double-blind, randomized, placebo-controlled clinical trial to determine if primary prophylaxis with hydroxychloroquine in healthcare workers reduces symptomatic COVID-19 infection. Healthcare workers will be randomized at a 1:1 allocation between intervention and placebo arms and followed for 12 weeks. This study will enroll up to 1,700 participates in Lafayette, Louisiana. The primary outcome will number of symptomatic COVID-19 infections. Secondary endpoints included number of days healthcare workers are absent from work and rate of severe infection.
Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay
Measure: Incidence of symptomatic COVID-19 infection in healthcare workers Time: 12 weeksDescription: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection
Measure: Absenteeism from work due to COVID-19 Time: 12 weeksDescription: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)
Measure: Severity of COVID-19 infection Time: 12 weeksCoronavirus (COVID-19) is a pandemic-like disease caused by a new coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-2) isolated in China in 2019. Clinical manifestations vary widely from one individual to another, from asymptomatic carrier to a febrile cough that can rapidly lead to acute respiratory distress syndrome. Since the beginning of the COVID-19 epidemic, screening by chest X-ray (RT) and polymerase chain reaction (PCR) SARS-CoV-2 conducted by the Cornwall Hospital Union laboratory has shown that among symptomatic patients and hospital staff suspected of being COVID-19, only 7.8% were attributable to COVID-19. Two nosocomial clusters were also identified, in the emergency department (10 carers) and in the cardiology department (6 carers and one patient). However, direct diagnosis by RT-PCR has sensitivity limits and can lead to false negative results when the subject is indeed suffering from COVID-19. This lack of sensitivity is inherent to the technique on the one hand, but also to the quality of the sample and the kinetics of the infection. Indeed, the virological window during which the virus is present in the respiratory mucous membranes sampled seems relatively narrow, hence a progressive negativation of the respiratory samples as the disease progresses. Moreover, clinical symptoms vary from one individual to another, and it is now recognized that some infected persons are asymptomatic but carry the virus. Thus, the use of a second diagnostic technique is a necessity, and serology could be a relevant diagnostic support. In the literature, several publications report the performance of COVID-19 serology in clusters of cases or cohorts of subjects. The serological techniques employed are variable (target epitopes in particular) and frequently homemade. Serology is mainly studied in comparison or association with RT-PCR in order to highlight the increased performance of COVID-19 diagnosis when the two techniques are combined. Correlation with chest CT imaging data is also encountered. Numerous serological tests are therefore being tested to determine retrospectively whether the individual has been exposed to the virus by looking for specific antibodies to the virus. The supreme health authority has drawn up specifications dated 16 April 2020, defining the methods for evaluating the performance of serological tests detecting antibodies directed against SARSCoV-2 in order to provide a framework for these practices. Several clinical studies are also underway, in particular to assess the kinetics of the appearance of the antibodies, whether these specific antibodies would be protective and whether their appearance would coincide with a cessation of contagiousness. Thus, the main objective of this study is to evaluate the diagnostic performance of the COVID-19 immunoglobulin (IgG) Dia-Pro serological test, in view of its deployment at the Cornish Hospital Union Laboratory. Subsequently, given the low prevalence of COVID-19 in Brittany and the risk of a second epidemic wave when the confinement is lifted, the evaluation of the seroprevalence of the staff of the Cornish Hospital Union is necessary in order to assess the attack rate of COVID-19 within the establishment and particularly within departments where nosocomial clusters have been reported; and to prevent the impact of deconfinement. Indeed, knowledge of the proportion of immunized personnel and its distribution according to services will make it possible to establish internal recommendations and to effectively manage personal protective equipment inventories, in conjunction with the deconfinement strategy that will be implemented by the government. The goal is to protect hospital staff from overexposure to the virus;
Description: The performance of the COVID-19 IgG Dia-Pro serological test is evaluated in terms of sensitivity/specificity.
Measure: Serological test evaluation Time: 1 dayDescription: Population seroprevalence among hospital staff (caregivers and non-caregivers) in Quimper Hospital is assessed
Measure: Population seroprevalence Time: 1 monthThis is a randomized, blinded phase 2 trial that will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms requiring oxygen supplementation.
Description: No clinical or virological evidence of infection Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death
Measure: Percentage of subjects reporting each severity rating on WHO ordinal scale for clinical improvement Time: 14 days post randomizationDescription: No clinical or virological evidence of infection Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death
Measure: Percentage of subjects reporting each severity rating on WHO ordinal scale for clinical improvement Time: 28 days post randomizationDescription: Anti-SARS-CoV-2 titers (IgM, IgG, IgA)
Measure: Comparison in Anti-SARS-CoV-2 antibody titers Time: 0, 1, 7, 14, 28, 90 days post randomizationDescription: SARS-CoV-2 PCR in nasopharyngeal swabs
Measure: Proportion positive in SARS-CoV-2 RNA Time: 0, 7, 14, 28 days post randomizationDescription: Rate of mortality
Measure: Mortality Time: 7, 14, 28 days post randomizationDescription: Percentage of patients requiring Intensive Care Unit admission
Measure: Rates of Intensive Care Unit admission Time: 7, 14, 28 days post randomizationDescription: Lymphocyte counts
Measure: Changes from baseline in lymphocyte Time: 0, 1, 3, 7, 14 days post randomizationDescription: Neutrophil counts
Measure: Changes from baseline in neutrophils Time: 0, 1, 3, 7, 14 days post randomizationDescription: D-dimer level
Measure: Changes from baseline in D-dimer Time: 0, 1, 3, 7, 14 days post randomizationDescription: Fibrinogen level
Measure: Changes from baseline in fibrinogen Time: 0, 1, 3, 7, 14 days post randomizationDescription: T cell subsets
Measure: Changes from baseline in T lymphocyte subsets Time: 0, 7, 28 days post randomizationDescription: B cell subsets
Measure: Changes from baseline in B lymphocyte subsets Time: 0, 1, 3, 7, 14 days post randomizationSuspension of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors and Adverse Outcomes in Hospitalized Patients With Coronavirus Infection.
Description: The primary outcome of the study will be days alive and outside the hospital (DAOH) at 30 days. This endpoint will be calculated for each included patient and the calculation will be from the date of randomization to the 30-day post-randomization. The DAOH endpoint represents the follow-up time (30 days) subtracted from the hospitalization days and/or the days between death and the end of follow-up.
Measure: Median days alive and out of the hospital Time: 30 daysDescription: Cardiovascular outcomes such as evolution with acute myocardial infarction, stroke, myocarditis, pericarditis, arrhythmias requiring treatment, thromboembolic phenomena, increase in troponin and D-dimer, respiratory failure, hemodynamic decompensation, sepsis, renal failure and death.All events will be reported according to CTCAE 4.0
Measure: Number of participants with adverse cardiovascular outcomes and new worsening heart failure Time: 30 daysDescription: Evaluation of test results troponin, NT-ProBNP, BNP, and D-dimer will also be assessed as secondary outcome.
Measure: Cardiovascular biomarkers related to COVID-19 Time: up to 30 daysThis study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in hospitalized patients with moderate COVID-19 disease.
Description: Number and severity of adverse events
Measure: Phase 1: Frequency and Severity of Adverse Events (AE) Time: Up to 12 monthsDescription: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR
Measure: Time to Clearance of SARS-CoV-2 Time: Up to 12 monthsDescription: Time from the date of randomization to the first date of clinical improvement of cough.
Measure: Time to Clinical Improvement of cough Time: Up to 28 daysDescription: Time from the date of randomization to the first date of clinical improvement of radiological evaluation of disease related chest x-ray
Measure: Time to Clinical Improvement in radiological evaluation of disease related chest x-ray Time: Up to 28 daysDescription: Proportion of subjects who achieve pulmonary clearance
Measure: Rate of Pulmonary Clearance Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of radiological evaluation of disease related chest x-ray
Measure: Rate of Clinical Improvement of radiological evaluation of disease related chest x-ray Time: Up to 28 daysDescription: Number and severity of adverse events
Measure: Phase 2: Frequency and Severity of Adverse Events (AE) Time: up to 12 monthsDescription: Time to medical discharge as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by time to medical discharge Time: up to 12 monthsDescription: Hospital utilization will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by hospital utilization Time: up to 12 monthsDescription: Mortality rate will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by measuring mortality rate Time: up to 12 monthsDescription: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.
Measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score Time: Up to 28 daysDescription: Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).
Measure: Time to Pulmonary Clearance Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of cough
Measure: Rate of Clinical Improvement of cough Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of fever
Measure: Rate of Clinical Improvement of fever Time: Up to 28 daysDescription: Time from the date of randomization to the first date of clinical improvement of fever
Measure: Time to Clinical Improvement of fever Time: Up to 28 daysDescription: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR
Measure: Rate of Clearance of SARS-CoV-2 Time: Up to 12 monthsSARS-CoV-2, has caused an international outbreak of respiratory illness termed Covid-19. The investigators used peptides derived from SARS-CoV-2 virus, to study viral-specific immune responses. COV-CREM is a French prospective monocentric study that will evaluate viral-specific cell responses in positive patients for SARS-CoV-2 on the basis of (RT-PCR) assay performed in respiratory tract sample tested by our local Center for Disease Control.
Description: Intensity and diversity of immune responses specific for SARS-COV-2
Measure: Specific immune responses Time: During COVID-19 infection or one month after COVID-19 infectionIdeal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.
Description: Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)
Measure: Progression of oxygenation needs Time: up to 1 monthDescription: Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.
Measure: Renal failure Time: up to 1 monthDescription: Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits
Measure: Liver failure Time: up to 1 monthDescription: Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)
Measure: Cytokine Storm Time: up to 1 monthDescription: Count of participants who die from COVID-19
Measure: Mortality Time: up to 1 month post hospital dischargeDescription: Length of hospital stay in days
Measure: Length of hospital stay Time: up to 1 monthDescription: Count of patients admitted to the ICU at any time during index hospitalization
Measure: Intensive Care Unit (ICU) admission Time: up to 1 monthDescription: Length of ICU stay in days
Measure: Intensive Care Unit (ICU) duration Time: up to 1 monthDescription: Count of participants requiring intubation
Measure: Intubation Time: up to 1 monthDescription: Length of intubation, measured in days
Measure: Intubation duration Time: up to 1 monthDescription: Time measured in days from hospital admission to determination patient is stable for discharge
Measure: Time until recovery Time: up to 1 monthItaly was the first European country affected by a severe outbreak of the Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic emerged from Wuhan region (China), with a high morbidity and mortality associated with the disease. In light of its pandemic spread and the very limited therapeutic options, COronaVIrus Disease 19 (COVID-19) is considered an unprecedented global health challenge. Therefore, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research. This is an interventional, non-pharmacological, open, randomized, prospective, non-profit study on the adjuvant use of oxygen ozone therapy plus probiotic supplementation in the early control of disease progression in patients with COVID-19. Contextually, all patients are treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of an ozone therapy-based intervention (accompanied by supplementation with probiotics) in containing the progression of COVID-19 and in preventing the need for hospitalization in intensive care units.
Description: Comparison between the two groups
Measure: Delta in the number of patients requiring orotracheal intubation despite treatment Time: 21 daysDescription: Comparison between the two groups
Measure: Delta of crude mortality Time: 21 daysDescription: Comparison between the two groups
Measure: Delta of length of stay for patients in hospital Time: 90 daysDescription: Comparison between the two groups
Measure: delta in the value of interleukin (IL)-1 Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of IL-6 Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of IL-10 Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of Tumor Necrosis Factor (TNF)-alpha Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR) Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of CD8+ CD38/ HLA-DR Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of fecal calprotectin Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of lipopolysaccharide (LPS) Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of zonulin Time: 21 daysDescription: Comparison between the two groups
Measure: delta in the value of alpha1-antitrypsin Time: 21 daysThis phase I/II trial studies low-dose radiation therapy as a focal anti-inflammatory treatment for patients with pneumonia or SARS associated with COVID-19 infection.
Description: The rate will be reported, along with a two-sided 95% exact binomial confidence interval, using the Clopper-Pearson method. The observed extubation rate will be compared to the null rate of 20% using a two-sided binomial test. Statistical significance is assessed at the 0.05 level.
Measure: Rate of extubation (for intubated patients) Time: Screening up to 28 days after radiation therapyDescription: Temperature in degrees (F)
Measure: Clinical outcome - Temperature Time: Screening up to 28 days after radiation therapyDescription: Heart rate in beats per minutes
Measure: Clinical outcome - Heart Rate Time: Screening up to 28 days after radiation therapyDescription: Systolic blood pressure in mm Hg
Measure: Clinical outcome - Systolic blood pressure Time: Screening up to 28 days after radiation therapyDescription: Oxygen saturation in percentage
Measure: Clinical outcome - Oxygenation Time: Screening up to 28 days after radiation therapyDescription: Respiratory rate in breaths per minute
Measure: Clinical outcome - Respirations Time: Screening up to 28 days after radiation therapyDescription: FI02 in percentage
Measure: Clinical outcome - FiO2 Time: Screening up to 28 days after radiation therapyDescription: Positive end expiratory pressure (PEEP) in cm H20
Measure: Clinical outcome - PEEP Time: Screening up to 28 days after radiation therapyDescription: Tidal volume in mL
Measure: Clinical outcome - Tidal volume Time: Screening up to 28 days after radiation therapyDescription: Extubation/intubation events in percentage
Measure: Clinical outcome - Intubation/Extubation events Time: Screening up to 28 days after radiation therapyDescription: Survival in percentage
Measure: Clinical outcome - Overall survival Time: Screening up to 28 days after radiation therapyDescription: Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS.
Measure: Radiographic outcome - Chest xray Time: Screening up to 28 days after radiation therapyDescription: CT scans with volume of consolidation measured in cubic centimeters.
Measure: Radiographic outcome - CT can Time: Screening up to 28 days after radiation therapyDescription: White blood cell count in cell count x 10^3/mcL
Measure: Serologic outcome - WBC Time: Screening up to 28 days after radiation therapyDescription: Hemoglobin in gm/dL
Measure: Serologic outcome - Hgb Time: Screening up to 28 days after radiation therapyDescription: Procalcitonin in ng/mL
Measure: Serologic outcome - Procalcitonin Time: Screening up to 28 days after radiation therapyDescription: Absolute neutrophil count in cell count x 10^3/mcL
Measure: Serologic outcome - ANC Time: Screening up to 28 days after radiation therapyDescription: Creatine kinase in units/L
Measure: Serologic outcome - Creatine kinase Time: Screening up to 28 days after radiation therapyDescription: Myoglobin in ng/mL
Measure: Serologic outcome - Myoglobin Time: Screening up to 28 days after radiation therapyDescription: Albumin in gm/dL
Measure: Serologic outcome - Albumin Time: Screening up to 28 days after radiation therapyDescription: Coagulation pathway time in seconds
Measure: Serologic outcome - PT/PTT Time: Screening up to 28 days after radiation therapyDescription: D-Dimer in ng/mL
Measure: Serologic outcome - D-Dimer Time: Screening up to 28 days after radiation therapyDescription: Gamma-glutamyl transferase in units/L
Measure: Serologic outcome - GGT Time: Screening up to 28 days after radiation therapyDescription: Trygliciericdes in mg/dL
Measure: Serologic outcome -Triglycerides Time: Screening up to 28 days after radiation therapyDescription: Ferritin in ng/mL
Measure: Serologic outcome -Ferritin Time: Screening up to 28 days after radiation therapyDescription: Fibrinogen in mg/dL
Measure: Serologic outcome -Fibrinogen Time: Screening up to 28 days after radiation therapyDescription: Immune marker flow cytometry (refractive index)
Measure: Serologic Immune markers flow cytometry Time: Screening up to 28 days after radiation therapyDescription: Bilirubin in mg/dL
Measure: Serologic outcome -Bilirubin Time: Screening up to 28 days after radiation therapyDescription: Lactate Dehydrogenase in units/L
Measure: Serologic outcome - LDH Time: Screening up to 28 days after radiation therapyDescription: Creatinine in mg/dL
Measure: Serologic outcome - Creatinine Time: Screening up to 28 days after radiation therapyDescription: Estimated Glomerular Filtration Rate in mL/min/m2
Measure: Serologic outcome - EGFR Time: Screening up to 28 days after radiation therapyDescription: C-Reactive Protein in mg/L
Measure: Serologic outcome - CRP Time: Screening up to 28 days after radiation therapyDescription: Alanine Aminotransferase in units/L
Measure: Serologic outcome - ALT Time: Screening up to 28 days after radiation therapyDescription: Asparatate Aminotransferase in units/L
Measure: Serologic outcome - AST Time: Screening up to 28 days after radiation therapyDescription: Troponin-I in ng/mL
Measure: Serologic outcome - Troponin-I Time: Screening up to 28 days after radiation therapyDescription: B-Natriuretic Peptid in pg/mL
Measure: Serologic outcome - BNP Time: Screening up to 28 days after radiation therapyDescription: pH (no unit)
Measure: Serologic outcome - Blood Gases pH Time: Screening up to 28 days after radiation therapyDescription: pressure of O2 in mm Hg
Measure: Serologic outcome - Blood Gases pO2 Time: Screening up to 28 days after radiation therapyDescription: pressure of CO2 in mm Hg
Measure: Serologic outcome - Blood Gases pCO2 Time: Screening up to 28 days after radiation therapyDescription: Lactic Acid in mmol/L
Measure: Serologic outcome - Lactic Acid Time: Screening up to 28 days after radiation therapyDescription: Interleukin-6 in pg/mL
Measure: Serologic outcome - IL-6 Time: Screening up to 28 days after radiation therapyDescription: Potassium in mmol/L
Measure: Serologic outcome - Potassium Time: Screening up to 28 days after radiation therapyThe administration of Calcifediol in patients with COVID-19, will reduce the development of SARS and the worsening of the various phases of the syndrome. Reducing at least 25% in ICU admission and death from the process, reducing days of hospitalization, facilitating the recovery of the same, acting significantly and positively, in any of its phases throughout the natural history of illness. As a treatment with extensive experience of clinical use, safe, inexpensive, and potentially very effective, it will have a highly efficient cost-benefit impact on the prevention of SARS.
Description: Proportion of subjects who enter the Intensive Care Unit
Measure: Admission to Intensive Care Unit Time: At day 28.Description: Proportion of subjects who die.
Measure: Death Time: At day 28.Description: Compare the time (in days) at discharge in newly hospitalized patients on non-invasive ventilation.
Measure: Time from onset of symptoms to discharge of patients in conventional hospitalization Time: At day 28.Description: In patients who, in the course of their evolution, required admission with mechanical ventilation in the ICU, time until admission to Intensive Care Unit
Measure: ICU - Time until admission Time: At day 28.Description: In patients who, in the course of their evolution, required admission with mechanical ventilation in the ICU, time until mechanical ventilation is removed.
Measure: ICU - Time mechanical ventilation is removed Time: At day 28.Description: Evaluation of the inflammatory markers related to IL disease. Blood samples will be collected and assessed in order to evaluate interleukins related with the interleukin storm using immunological tests.
Measure: Evaluation of the inflammatory markers related with the disease Time: At day 28.Description: Evaluation of the Vitamin D metabolites.
Measure: Vitamin D metabolites Time: At day 28.Description: Compare the evolution in SatO2
Measure: Evolution in SatO2 Time: At day 28.Description: Compare the evolution in the Sat O2/FiO2 ratio
Measure: Evolution in the Sat O2/FiO2 ratio. Time: At day 28.Description: Compare the evolution in the degree of dyspnea using the analog Borg scale
Measure: Evolution in the degree of dyspnea Time: At day 28.Description: Compare the evolution of radiological findings by simple radiology in the recruited subjects since their beginning in the trial until they end the trial
Measure: Evolution of the improvement of radiological findings by simple radiology Time: At day 28.Description: Incidence of adverse events related to medication and its administration.
Measure: Incidence of adverse events Time: At day 28.Description: Incidence in the appearance of hemorrhagic or thrombotic phenomena.
Measure: Appearance of hemorrhagic or thrombotic phenomena Time: At day 28.This study is a case-control study to characterize the molecular and cellular anomalies of the olfactory epithelium of COVID-19 patients with isolated anosmia, by comparison with the olfactory epithelium of non-infected subjects.
Description: Ratio of olfactory sensory cells in the nasal cytological sample
Measure: Molecular and cellular defects in olfactory epithelium Time: 30 monthsDescription: Multiple measurements will be analyzed to characterize the immune and inflamatory status of the olfactory mucosa (presence of infiltrated immune cells, activation state of the immune cells in the epithelium, cytokine and interleukin level)
Measure: Biological mechanisms involved in the pathogenesis of the disease Time: 30 monthsDescription: Demographic variables (sex, age, blood type), risk factors (tobacco, overweight, diabetes, rhinosinusitis disease, respiratory allergy)
Measure: Epidemiological characteristics Time: 30 monthsDescription: Self-questionnaire taste and smell survey (TTS)
Measure: Olfactory and taste dysfunction Time: 30 monthsDescription: Visual analogue scale (VAS) (units from 0 normal perception to 100 no perception)
Measure: Olfactory and taste dysfunction Time: 30 monthsElectrocardiographic (ECG) evaluation of patients with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection. The present study involves three different phases of evaluation of the ECG traces of hospitalized patients with SARS-CoV-2 infection. - Phase 1: it is proposed to collect and retrospectively analyze the ECGs of hospitalized patients with severe SARS-CoV-2 infection which led to invasive ventilation or patient death as a consequence and, if available, also possible troponin dosage; - Phase 2: aims to collect and analyze the ECGs of consecutive hospitalized patients with SARS-CoV-2 infection and evaluate their relationship with the course of the disease, cardiac involvement and prognosis; - Phase 3: it is proposed to repeat ECG and to carry out echocardiogram to patients with SARS-CoV-2 infection after 3 months from hospital discharge by simultaneously performing, if deemed clinically indicated, also cardiac magnetic resonance. In this phase, any evolutions of ECG alterations of the acute phase will be described and the relationship with cardiac involvement will be assessed.
Description: Describe the ECG characteristics in patients presenting with severe form of SARS-CoV-2 infection
Measure: Phase 1: ECG characteristics in patients presenting with severe form of SARS-CoV-2 infection Time: 1 monthDescription: To evaluate the correlation between ECG signs and cardiac involvement in the acute phase • Assess the correlation between ECG signs and mortality in the acute phase
Measure: Phase 2: Correlation between ECG signs and needs for invasive mechanical ventilation and/or mortality in the acute phase Time: 6 monthsDescription: To evaluate the correlation between acute phase ECG signs and chronic phase cardiac involvement • evaluate the appearance, in the short-term follow-up, of signs of cardiac involvement (cardiomyopathies and conduction disorders in particular)
Measure: Phase 3: Correlation between ECG signs and cardiac involvement and mortality in the chronic phase Time: 12 monthsThe infectious disease COVID-19, caused by coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has been declared a pandemic and an international healthcare emergency by the World Health Organization (WHO). It has spread across the globe, overwhelming healthcare systems by causing high rates of critical illness. Mortality from COVID-19 exceeds 4%, with older people with comorbidities being extremely vulnerable. It is expected that between 50-80% of the world's population may contract SARS-CoV-2 over the next two years. It is expected that the outcomes will be potentially worse in Africa, because firstly, there is a limited workforce, and secondly there are limited intensive care facilities and critical care resources across Africa to provide sufficient care. It is important therefore to establish what resources, comorbidities and interventions are potentially associated with either mortality or survival in patients with COVID-19 who are referred for critical care in Africa. Rapid dissemination of these findings may help mitigate mortality from COVID-19 in critical care patients in Africa. These points provide the rationale for the African COVID-19 Critical Care Outcomes Study (ACCCOS).
Description: The primary outcome is in-hospital mortality in adult patients referred to intensive care or high-care units following suspected or known COVID-19 infection in Africa.
Measure: In-hospital mortality Time: 8-12 monthsDescription: To determine the risk factors (resources, comorbidities and interventions) associated with mortality in adult patients with suspected or known COVID-19 infection in Africa.
Measure: Risk factors (resources, comorbidities and interventions) associated with mortality Time: 8-12 monthsProspective registry for multimodal assessment of neuromuscular pathology associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, enrolling consecutive patients with corona virus disease 2019 (Covid-19), who are admitted to the intensive care unit of the department of anesthesiology and intensive care medicine, or the department of neurology at Tübingen University Hospital.
Description: Elevation of creatine kinase during hyperacute phase of corona virus disease 2019 (Covid-19)
Measure: Rate of elevated creatine kinase in hyperacute phase Time: 1 weekDescription: Elevation of creatine kinase during hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Rate of elevated creatine kinase Time: 24 monthsDescription: Two-peak elevation of creatine kinase during acute phase of corona virus disease 2019 (Covid-19)
Measure: Rate of two-peak elevation of creatine kinase during acute phase Time: 30 daysDescription: Presence of myositis-specific antibodies on admission, at two weeks, and at end of follow-up
Measure: Rate of myositis-specific antibodies Time: 24 monthsDescription: Presence of antimyocardial antibodies on admission, at two weeks, and at end of follow-up
Measure: Rate of antimyocardial antibodies Time: 24 monthsDescription: Level of creatine kinase elevation in the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19) assessed by the area under the curve (AUC)
Measure: Area under the curve (AUC) of elevated creatine kinase Time: 24 monthsDescription: Maximal value of creatine kinase elevation in the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Peak-levels of elevated creatine kinase Time: 24 monthsDescription: Maximal value of troponin in the acute phase of corona virus disease 2019 (Covid-19)
Measure: Peak-levels of troponin Time: 30 daysDescription: Maximal value of urine myoglobin in the acute of corona virus disease 2019 (Covid-19)
Measure: Peak-levels of urine myoglobin Time: 30 daysDescription: Muscle hyperechogenicity in the upper and lower extremities, the accessory respiratory serratus anterior muscle, and abdominal wall according to qualitative ultrasound assessment (Heckmatt score) during the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Rate of muscle hyperechogenicity Time: 24 monthsDescription: Peak-muscle hyperechogenicity in the upper and lower extremities, the accessory respiratory serratus anterior muscle, and abdominal wall according to qualitative ultrasound assessment (Heckmatt score) during the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Peak-muscle hyperechogenicity Time: 24 monthsCoronavirus COVID-19 is an emerging virus also called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Eighty percent of patients are poor or asymptomatic. However, there are major respiratory complications for some patients, requiring intensive care hospitalization and possibly leading to death in 5% of cases. One of the hypotheses put forward is that much of the pathophysiology is due to endothelial dysfunction associated with disseminated intravascular coagulation. The covid-19 pathology could induce coagulation impairment as observed during sepsis. An increase in D-dimer levels during covid-19 disease is itself associated with excess mortality. While D-dimers are highly sensitive, they are not specific for clotting activity. They may be increased in many other circumstances, particularly in inflammation. On the other hand, the infection stimulates the release of extracellular vesicles. These vesicles, of multiple cellular origin, are an actor of vascular homeostasis, and participate in the state of hyperactivation of coagulation. They have a major role in the prothrombotic state and the development of coagulopathy associated with sepsis. The aim of our monocentric prospective study would be to study early and more specific markers of hypercoagulability and markers of routine endothelial dysfunction, as soon as the patient is hospitalized, in order to predict the risk of hospitalization in intensive care.
Description: Biological analysis using initial blood sampling
Measure: D-DIMERS plasma levels in blood Time: 1 hour after admissionDescription: Biological analysis using initial blood sampling
Measure: Fibrin monomers plasma levels in blood Time: 1 hour after admissionDescription: Biological analysis using initial blood sampling
Measure: Antithrombin plasma levels in blood Time: 1 hour after admissionDescription: Biological analysis using initial blood sampling
Measure: Prothrombin Fragment 1 plasma levels in blood Time: 1 hour after admissionDescription: Biological analysis using initial blood sampling
Measure: Prothrombin Fragment 2 plasma levels in blood Time: 1 hour after admissionDescription: Biological analysis using initial blood sampling
Measure: Thrombin generation test plasma levels in blood Time: 1 hour after admissionDescription: Biological analysis using initial blood sampling
Measure: Microvesicles of platelet plasma levels in blood Time: 1 hour after admissionDescription: Biological analysis using initial blood sampling
Measure: Cross-linked platelets plasma levels in blood Time: 1 hour after admissionDescription: Biological analysis using initial blood sampling
Measure: Willebrand Factor plasma levels in blood Time: 1 hour after admissionDescription: Biological analysis using initial blood sampling
Measure: Factor VIII plasma levels in blood Time: 1 hour after admissionPurpose: To determine the number of asymptomatic individuals who have antibodies to SARS-CoV-2, the virus which causes COVID-19
Description: Presence or absence of IgG antibodies to SARS-CoV2
Measure: Percentage of Asymptomatic patients with an IgG response from SARS-CoV-2 infection. Time: at enrollmentDescription: swab for presence of SARS-CoV-2 virus
Measure: Percentage of Asymptomatic patients with viral presence of SARS-CoV-2 infection. Time: at enrollmentThe novel coronavirus (SARS-CoV-2) has spread all around the world and testing has posed a challenge globally. Health care providers are highly exposed and are an important group to test. On top of these concerns, health care workers are also stressed by the needs on responders in the COVID-19 crisis. The investigators will look at different ways to measure how common COVID-19 is among health care workers, how common is the presence of antibodies by serological tests (also known as serostatus). The investigators will describe health worker mental and emotional well-being and their coping strategies in their institutional settings. Lastly, the investigators will describe how knowing serostatus can affect individuals' mental and emotional well-being and how to cope in the midst of the COVID-19 response. This will help to how to better test and help healthcare workers in the COVID-19 pandemic and prepare for possible future outbreaks.
Description: Percentage of health care workers with positive serological markers to describe patterns in exposure, re-infection, clinical symptom, serological responses among health care workers based on their baseline serological status over a one year period.
Measure: Proportion seropositive Time: Up to 12 months after collection visitThis concerns a single-center prospective interventional cohort study. Laboratory-confirmed COVID-19 patients will be asked to donate blood at at least two different timepoints. This will allow us to investigate T and B cell evolutions during the course of infection and recovery. The expected duration of the study is four months or the total duration of the SARS-CoV-2 circulation in Belgium (whichever is shortest).
This is a compassionate use, proof of concept, phase IIb, prospective, interventional, pilot study in which the investigators will evaluate the effects of compassionate-use treatment with IV tirofiban 25 mcg/kg, associated with acetylsalicylic acid IV, clopidogrel PO and fondaparinux 2.5 mg s/c, in patients affected by severe respiratory failure in Covid-19 associated pneumonia who underwent treatment with continuous positive airway pressure (CPAP).
Description: Change in ratio between partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, and inspired oxygen fraction at baseline and after study treatment
Measure: P/F ratio Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Change in partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: PaO2 difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Change in alveolar-arterial gradient of oxygen at baseline and after study treatment. Arterial alveolar gradient will be calculated using the following parameters derived from arterial blood gas analysis: partial pressure of oxygen in arterial blood and partial pressure of carbon dioxide in arterial blood.
Measure: A-a O2 difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Number of days on continuous positive end expiratory pressure (CPAP)
Measure: CPAP duration Time: From the first day of study drugs administration (T0) until day 7 post study drugs administrationDescription: Difference in intensity of the respiratory support (non invasive mechanical ventilation, CPAP, high flow nasal cannula (HFNC), Venturi Mask, nasal cannula, from higher to lower intensity, respectively) employed at baseline and at 72 and 168 hours after study treatment initiation
Measure: In-hospital change in intensity of the respiratory support Time: At baseline and 72 and 168 hours after treatment initiationDescription: Difference in partial pressure of carbon dioxide in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: PaCO2 difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in concentration of bicarbonate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: HCO3- difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in concentration of lactate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment
Measure: Lactate difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in hemoglobin concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.
Measure: Hb difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Difference in platelet concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.
Measure: Plt difference Time: At baseline and 24, 48 and 168 hours after treatment initiationDescription: Any major or minor adverse effect occuring during and after the administration of the study drug (e.g. bleeding)
Measure: Adverse effects Time: From the first day of study drugs administration until day 30 post study drugs administrationSARS-CoV-2 induces over-production of inflammatory cytokines, and especially interleukin-6 (IL-6). The apparently strong association between blood levels of inflammaory cytokines and SARS-CoV-2 disease severity has led clinicians to evaluate the administration of steroids or anti-IL-6 antagonists in severely ill patients. As of this day, biomarkers capable of predicting clinical disease progression in Covid-19 patients with mild-to-moderate symptoms have not yet been formally identified. Identifying such markers and evaluating their predictive value may be exploited to guide patient care management, and as such forms the core objective of this proposal. Because of strong inter-individual variations in the ability of innate immune cells to produce cytokines, the hypothesis formulate and intend to test is that innate IL-6 responsiveness varies between recently infected Covid-19 patients and could predict disease outcome. To test this hypothesis, the investigator propose to follow recently infected kidney transplant patients with moderate Covid-19 symptoms. These patients stand a higher risk to progress to severe disease. The staff plan to collect a blood sample in these patients using a system whereby ex vivo cytokine production is initiated in the very same blood collection tube without prior separation and centrifugation, thus reducing labour and operator bias. After incubation with or without known innate immune stimuli, the cell-free phase from each collection-culture tube will be assayed for IL-6 content. Associations between IL-6 content and disease outcome (encephalopathy, transfer to acute care or death) will be determined in 115 Covid-19 kidney transplant patients with moderate symptoms followed in 9 centers.
Description: quantity of IL-6 in of whole blood samples after ex vivo co-stimulation with LPS and ATP in Covid-19 kidney transplant patients.
Measure: Predictive value of IL-6 contents of whole blood samples after ex vivo stimulation Time: 10 monthsTo compare various treatments provided to positive COVID-19 patients at locations across the OSF Ministry. Provide the opportunity to compare the effectiveness of various treatments and treatment timelines provided to specific cohorts of patients that have the potential to impact future treatment plans for COVID-19 patients and/or future research hypotheses.
Hungarian CoronaVirus disease-19 Epidemiological Research
Description: The rate of the infected patients, asymptomatic carrier and healed patients
Measure: COVID-19 rate Time: 1 yearPatient are being asked to provide respiratory and blood samples for a clinical research study because the patients have a virus called the novel coronavirus, or SARS-CoV-2, that causes the disease known as Covid-19. Investigators do not know a lot about this virus, including all the ways it travels from person to person. Investigators also do not know if a person will get sick or not from the virus after being in close contact with someone who has the virus. Because of this, investigators are performing research on the virus found in respiratory secretions to get more information on how investigators can best detect and treat this new virus in the future. Primary Objective - To determine the clinical characteristics and outcomes of Covid-19 in children. - To characterize the clinical risk factors of Covid-19 in children.. Secondary Objectives - To characterize the immunological risk factors and serologic response to SARS-CoV-2 infection in children.- To evaluate the duration of viral shedding in children. - To evaluate the duration of SARS-CoV-2 viral shedding in children. Exploratory Objective
Description: Clinical characteristics, including demographics, underlying diagnosis, and signs/symptoms, and outcomes, such as hospitalization, oxygen requirements, and mortality, will be summarized with counts and percentages.
Measure: Characteristics and outcomes of acute respiratory infections due to COVID-19 in children. Time: Baseline-Day 60Description: Pearson or Spearman's correlation of clinical risk factors such as age, underlying diagnosis, immunosuppression with outcomes as detailed in primary objective 1 will be evaluated.
Measure: Clinical risk factors of acute respiratory infection due to COVID-19 in children. Time: Baseline-day 60Description: Immunological (e.g., Absolute lymphocyte/monocyte counts, Immunoglobulin level) and serological (antibodies against the virus) response measures will be summarized with mean, standard deviation, median and range.
Measure: Immunologic response to acute respiratory infection due to COVID-19 in children. Time: Baseline-day 60Description: The duration of viral shedding, defined as the time between the first positive test date and the first negative test date, will be summarized for all participants with mean, standard deviation, median and range.
Measure: Duration of viral shedding and evolution in children longitudinally. Time: Baseline-Day 60The objectives of PROVIDE are to: 1. Determine if prophylactic once weekly hydroxychloroquine reduces the incidence of conversion from SARS-2-CoVnasopharyngeal swab negative to positive 2. To determine if weekly prophylactic hydroxychloroquine reduced the severity of COVID-19 symptoms 3. To determine the safety of taking weekly prophylactic hydroxychloroquine
Description: The number of HCW that tested positive for SARS-CoV-2
Measure: Positive for SARS-CoV-2 Time: 8 weeksDescription: The number of HCW that required hospital admission secondary to SARS-CoV-2
Measure: Hospital admissions Time: at any time after first dose to hospital discharge, truncated at 60 daysDescription: The number of HCW that required intensive care unit admission
Measure: Intensive care unit admissions Time: at any time after first dose to hospital discharge, truncated at 60 daysDescription: The number of HCW that required intubation and mechanical ventilation
Measure: Intubation and mechanical ventilation Time: at any time after first dose, truncated at 60 daysDescription: number of days admitted to the ICU
Measure: ICU length of stay Time: from randomization to hospital discharge, truncated at 60 daysDescription: number of days admitted to the hospital
Measure: Hospital length of stay Time: from randomization to hospital discharge, truncated at 60 daysDescription: Death
Measure: Mortality Time: from randomization to 60 daysDescription: Gastrointestinal symptoms (abdominal pain, diarrhea, nausea, vomiting), Hypoglycemia, Abdominal LFTs, Angioedema, Opthalmic (corneal changes, decreased visual acuity, macular degeneration, retinal changes), Bronchospasm
Measure: Incidence of adverse events Time: from randomization to 60 daysCOHIVE is an observational cohort nested in four antiretroviral therapy research studies (ADVANCE - NCT03122262; D²EFT - NCT03017872; DolPHIN2 - NCT03249181 and NAMSAL-ANRS12313 - NCT02777229). COHIVE will include participants who are possible COVID-19 cases with symptoms or confirmed COVID-19 cases, and participants who agree to have a serology testing for SARS-CoV-2 regardless of COVID-19 history.
Description: To characterise the clinical features of symptomatic COVID-19 in PLWH (cardio-respiratory and other clinical signs or symptoms), described overall and by HIV and comorbid disease factors including pregnancy status.
Measure: Clinical features of symptomatic COVID-19 in people living with HIV (PLWH) Time: At baselineDescription: To characterise the clinical outcomes of symptomatic COVID-19 in PLWH, assessing the outcomes of patients including the percentage of patients who are fully recovered, required hospitalisation, developed severe illness (ICU admission or equivalent) or died.
Measure: Clinical outcomes of symptomatic COVID-19 in PLWH Time: At Day 28Description: To characterise the clinical outcomes of symptomatic COVID-19 in PLWH, assessing the outcomes of patients including the percentage of patients who are fully recovered, required hospitalisation, developed severe illness (ICU admission or equivalent) or died.
Measure: Clinical outcomes of symptomatic COVID-19 in PLWH Time: At Month 3Description: To determine seroprevalence of COVID-19 in all parent study participants regardless of COVID-19 history.
Measure: Seroprevalence of COVID-19 in all parent study participants Time: Through study completion, an average of one yearThe coronavirus disease 2019 (COVID-19) is an emerging pandemic in 2020 caused by a novel coronavirus named SARS-CoV2. Diabetes confers a significant additional risk for COVID-19 patients. Dipeptidyl peptidase 4 (DPP-4) is a transmembrane glycoprotein expressed ubiquitously in many tissues. In addition to its effect on glucose levels, DPP-4 has various effects on the immune system and several diseases, including lung diseases. This trial aims to assess the safety and efficacy of linagliptin, a DPP-4 inhibitor, in the treatment of COVID-19. The trial will be randomized without blinding, with one are treated by insulin only for glucose balance and the other by insulin and linagliptin. The trial will assess the effects of linagliptin on different measures of COVID-19 recovery.
Description: Clinical change is defined as 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19: 0 - No clinical or virological evidence of infection; 1 - No limitation of activities; 2 - Limitation of activities; 3 - Hospitalized, no oxygen therapy; 4 - Oxygen by mask or nasal prongs; 5 - Non-invasive ventilation or high-flow oxygen; 6 - Intubation and mechanical ventilation; 7 - Ventilation + additional organ support - pressors, renal replacement therapy, extracorporeal membrane oxygenation; 8 - Death.
Measure: Time to clinical change Time: 28 daysDescription: Percent of patients with a 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19.
Measure: Percent of patients with clinical improvement. Time: 28 daysThe aim of this study is to determine the risk factors for development of ventilator-associated pneumonia (VAP) and to identify the prognostic factors of VAP among Coronavirus Disease 2019 (CoViD-19) patients. We hypothesized that CoViD-19 serves as a high risk factor for the development of VAP and it affects clinical outcome measures negatively.
Currently we do not know how best to treat patients infected with COVID-19. This study is looking at whether randomising participants to either a combination of azithromycin, hydroxychloroquine and zinc or favipiravir, alongside usual care, can help patients with suspected or proven COVID-19 infection.
Description: Time from randomisation to clinical improvement by two points on a seven-category ordinal scale: Not hospitalised with resumption of normal activities Not hospitalised, but unable to resume normal Hospitalised, not requiring supplemental oxygen Hospitalised, requiring supplemental oxygen Hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation or both Hospitalised, requiring ECMO (Extra-corporal membrane oxygenation), invasive mechanical ventilation or both Death
Measure: Time to improvement by two points on a seven-category ordinal scale Time: Up to 28 days from randomisationDescription: Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale)
Measure: Clinical status on a seven-category ordinal scale (Day 7) Time: Day 7 from randomisationDescription: Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale)
Measure: Clinical status on a seven-category ordinal scale (Day 14) Time: Day 14 from randomisationDescription: Survival of patients to end of study
Measure: Overall survival Time: 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS score of patient condition, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS score Time: Up to 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS element score for temperature, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS element score for temperature Time: Up to 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS element score for heartrate, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS element score for heartrate Time: Up to 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS element score for respiratory rate, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS element score for respiratory rate Time: Up to 28 days from randomisationDescription: Time from randomisation to improvement by two points on the NEWS element score for oxygen saturation, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
Measure: Time to improvement by two points on the NEWS element score for oxygen saturation. Time: Up to 28 days from randomisationDescription: Frequency of admission of patients to intensive care
Measure: Admission to intensive care Time: Up to 28 days from randomisationDescription: Frequency of requirement to administer mechanical ventilation to patients
Measure: Requirement for mechanical ventilation Time: Up to 28 days from randomisationDescription: Frequency of requirement to administer non-invasive ventilation, continuous positive airways pressure or high-flow oxygen to patients
Measure: Requirement for non-invasive ventilation, continuous positive airways pressure or high-flow oxygen Time: Up to 28 days from randomisationDescription: Frequency of culture-confirmed bacterial or fungal infection in patients
Measure: Incidence of bacterial or fungal infection Time: Up to 28 days from randomisationDescription: Frequency and severity of adverse events in patients not directly attributed by clinicians to COVID-19 infection.
Measure: Incidence of adverse events not directly caused by COVID-19 infection. Time: Up to 28 days from randomisation.Description: Frequency of readmission to inpatient care of patients discharged from hospital.
Measure: Readmission to inpatient care Time: Up to 28 days from randomisationThe primary objective of this multi-center study is to clarify the value of a CRP measurement for triage of patients initially presenting with light symptoms of the COVID-19 infection. Current recommendations of management of COVID-19 include large-scale tests for virus. Such tests reveal whether an individual is infected with the virus, however, the demonstration of virus per se has no prognostic value for the ensuing course of the COVID-19 disease. Publications of possible treatments strategies increase exponentially, while evidence of triage of the affected individuals is mainly based on the level of pulmonary affection as measured by the Oxygen saturation. To inform decision making for which patients are to be hospitalized due to risk of developing more severe affection, this study addresses the question, whether triage may be performed with the aid of a simple CRP measurement.
Description: Admission to a hospital. Reason for admission is recorded.
Measure: Hospitalisation Time: within 28 daysThis is a single arm phase II trial to assess efficacy and confirm safety of infusions of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms,with or without confirmed interstitial COVID-19 pneumonia by chest Xray or CT. A total of 29 eligible subjects will be enrolled to receive anti-SARS-CoV-2 plasma.Outcomes will be compared to hospitalized controls with confirmed COVID-19 disease through retrospective chart review.
Description: Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.
Measure: Transfer to ICU Time: Days 0 - 60Description: Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.
Measure: 28 day mortality Time: Days 0 - 60Description: Will be collected from time of enrollment until completion of the study. The adverse events will be evaluated by CTCAE V5.0 and MedDRA.
Measure: Cumulative incidence of serious adverse events Time: Days 0 - 60Description: Will be done by collecting respiratory tract swabs and testing for SARS-CoV-2 positivity.
Measure: Rates and duration of SARS-CoV-2 Time: Days 0, 7, 14, and 21Description: Serum or plasma will be collected and analyzed for SARS-CoV-2 antibody.
Measure: Serum of plasma antibody titer to SARS-CoV-2 Time: Days 0, 7, 14, and 28Description: Blood will be collected and analyzed for cellular and humoral response.
Measure: Cellular and humoral immune response Time: Days 0, 7, 14, 28Description: All days where a supplemental oxygen is needed will be recorded as a concomitant medication and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the supplemental oxygen free days.
Measure: Supplemental oxygen free days Time: Days 0-28Description: All days where a ventilator is needed will be recorded as a concomitant procedure and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ventilator free days.
Measure: Ventilator free days Time: Days 0 - 28Description: All days where the participant is admitted to the ICU will be recorded and subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ICU free days.
Measure: ICU free days Time: Days 0 - 28Description: The patient will be evaluated throughout their enrollment in the study. The score will be evaluated to see if the score improved or worsened throughout their admission.
Measure: Sequential organ failure assessment score Time: days 0, 1, 4, 7, 14, 21, 28Description: Concomitant medications will be recorded throughout the patients participation in the study and vasopressors will be recorded, if they are needed.
Measure: Need for vasopressors Time: Days 0 - 60Description: Renal function will be assessed throughout the patients participation in the study. If renal replacement therapy is needed, it will be captured as a concomitant procedure.
Measure: Need for renal replacement therapy Time: Days 0 - 60Description: Respiratory function will be assessed throughout the patients participation in the study. If ECMO is needed, it will be captured as a concomitant procedure.
Measure: Need for extracorporeal membrane oxygenation (ECMO) Time: Days 0 - 60Description: Will be calculated from the date the patient entered the hospital until they were discharged.
Measure: Hospital length of stay (LOS) Time: Days 0-60Description: Will be calculated from the date the patient entered the ICU until they were discharged from the ICU.
Measure: ICU LOS Time: days 0 - 60Description: All adverse events will be recorded and evaluated by CTCAE v.5.0. All grade 3 and 4 AEs will be calculated to determine safety of convalescent plasma.
Measure: Grade 3 or 4 Adverse Events (AEs) Time: days 0 - 60Severe COVID-19 patients at a high risk of venous thromboembolism. We studied patients in 2 intensive care units of university hospitals in Barcelona and Badalona, Spain. We performed a cut-off screening of deep venous thrombosis (DVT) with bilateral duplex ultrasound to 230 patients.
Description: Patients with symptomatic pulmonary embolism confirmed on the CT-angiography and those with a swollen limb and confirmed deep venous thrombosis on compression ultrasound were considered to have "symptomatic venous thromboembolisms". The remaining patients with positive limb ultrasound or CT-angiography were considered to have "asymptomatic venous thrombembolism"
Measure: Venous thromboembolisms Time: 7 daysDescription: Deaths from all causes during the follow-up
Measure: Deaths Time: 7 daysAcute respiratory failure (ARF) is a common condition and a common reason for urgent medical consultation. Assessing the extent of respiratory impairment is important to improve the management of patients with ARF. When Acute respiratory failure is caused by pathology of the pulmonary parenchyma, quantification of pulmonary radiographic involvement may be a component of the initial assessment of severity. This radiographic quantification would only be usable in clinical routine if it can be automated and provide a real-time result. The objective of this work is to assess the feasibility of an automated technique for quantifying radiological lung damage in situations of known or potential ARF.
Currently there is no standard treatment for SARS-CoV-2 infection. Use of convalescent plasma has been studied in outbreaks of other respiratory infections, including SARS-CoV-1 , MERS-CoV and Hantavirus infection. This study is an open-label randomized trial in which patients with high risk of COVID19-associated respiratory failure will be randomized to early treatment with convalescent plasma (< 7 days from symptoms start) or at early signs of respiratory failure or prolonged hospitalization. COVID-19 convalescent plasma will be collected from individuals according to the institutional protocol.
Description: Days
Measure: Median duration of fever Time: 1 yearDescription: Days
Measure: Median duration of mechanical ventilation Time: 1 year follow upDescription: Days
Measure: Median length of ICU stay Time: 1 year follow upDescription: Days
Measure: Median length of admission Time: 1 year follow upDescription: days
Measure: Median length of viral clearance Time: 1 year follow upSARS-CoV-2 belong to beta-coronavirus family and its transmission route and symptoms follow those of all community-acquired coronaviruses. The main difference of the novel Coronavirus is the higher mortality rate, that is around 3%. Death rate is over 1% only for patients over 50 years old, whereas until 40 years old is under 0,4%. No fatalities are declared among children under 10 years old to date. Death rate is almost double for male rather than female. This distribution of mortality rate according to age of infected patients could be only partially ascribed to other comorbidities in addition to great age. In fact, patients with no pre-existing conditions have however a case fatality rate of 0,9%. The almost null rate of severe illness in children and generally in patients younger than 40 years old is quite un-explicable. Infant, children and young people could be infected but infection is rapidly self-limited or without symptoms. Older patients undergo severe lung injury as consequence of an immune response that is late in coming. Possible explanation of these phenomena could be something, which assure ability to prompt response to SARS-CoV-2 in younger people independently from the novelty of the virus itself. It would seem to be that younger people are already sensitized to the antigens of the virus without a previous contact. This immunity is not really specific, but "partially specific" for many antigens of the virus, however able to limit the infection in the organism. Something stimulated the immune system and it scattered immunity against more and more antigens present. Children are the age group mostly exposed to all community-circulating viruses. This immunity is not persistent but progressively fade out. It protects from the age of two, when the hypothetical stimulation occurs, to the fifth decade because of its slow decrease. The only external stimulation, which healthy people receive are vaccines. All vaccinations and especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis could stimulate immune system. They develop the specific immunity but generate also a sprouting immunity against antigens in transit, as coronaviruses and other community-circulating viruses. The developed immunity gives some protection against multiple viral infection for years until the natural fade out. After the fifth decade, that immunity is slower to be recall and reactivated. Additionally, transplant recipients and HIV infected patients, which have an immune system inhibited, unexpectedly, do not seem to suffer the worst complications of SARS-CoV-2 infection. An immune system imbalance could be play a pivotal role during the reaction to the virus, limiting destructive consequences of excessive inflammation. According to the medical hypothesis on which the protocol is based on, young people could benefit from a functional adaptation of innate immune cells induced through epigenetic reprogramming and, especially, a pre-existing "partially specific" immunity to the community viruses caused by "bystander effect" of preceding vaccinations. In this study, we will explore the main differences existing among patients infected by SARS-CoV-2 who experience the illness at different degree of severity. We suppose to recognize different populations of patients, each one with a specific immunological pattern. It could differ in terms of cytokines, soluble factors serum level and immune cells activity both of the innate compartment and of the acquired one. The proof of a role of these immunological phenomena in the pathogenesis of Covid-19 are bases for implementation of therapeutic immunomodulatory treatments. In addition, the definition of an immunological risk profile could tailor established therapies to each kind of patient.
Description: Scientists' hypothesis is that monocytes, NK, CD4 AND CD8 T cells, in patients with severe infection to SARS-CoV-2, show an impairment in their function: cells reveal an overpowering hyperactivity that provokes a pathologic inflammatory response with a massive production of proinflammatory cytokine, edema and pulmonary fibrosis.
Measure: Immune cells activity Time: 6 monthsDescription: The secondary objectives are to correlate clinical data and vaccination history with laboratory immune pattern to identify protective factors for Covid 19 and open paths for new therapeutic strategies.
Measure: Protective factors and new therapeutic strategies Time: 6 monthsThis is a prospective study, involving contacting potential plasma donors and the use of their plasma to help fight off infections of those suffering from COVID19 in accordance to collection guidelines for plasma and FDA IND requirement. This study will include up to 240 participants potentially receiving convalescent plasma and up to 1000 potential donors. There are 3 basic arms to the study: mild, moderate and severe/critical severity. All 3 severity groups are eligible for enrollment, but mild severity will not be given plasma unless there is progression. Moderate severity will given up to 1 unit of plasma and severe/critical severity up to 2 units. There is no placebo group, however given the excepted issues of shortages of plasma, intention to treat will be used for analysis.
Description: Time it takes to identify eligible donors whom are willing to donate
Measure: Plasma Donor Time: Measured in days for 365 daysDescription: Time it takes the plasma collection center to contact willing donors whom are allowed to donate plasma
Measure: Plasma Donor Time: Measured in days for 365 daysDescription: Time from consent to infusion
Measure: Plasma Recipient Time: Measured evey 24 hours up to 30 daysDescription: Survival
Measure: Plasma Recipient Time: Measured in days with 30 day from discharge follow-upDescription: Time until plasma is donated
Measure: Plasma Donor Time: Measured every 24 hours up to 1 yearDescription: Incident of treatment-Emergent Adverse Events [Safety and Tolerability]
Measure: Plasma Recipient Time: Day 1, 2, 3, 4, 7, and 30 dayDescription: Morbidity reduction
Measure: Plasma Recipient Time: Day 1, 2, 3, 4, 7, and 30 dayDescription: Reduced Length of Stay in hospital
Measure: Plasma Recipient Time: Measured every 24 hours until patient discharged from hospital up to 1 yearDescription: Reduced Length of Stay on Advance Respiratory Support
Measure: Plasma Recipient Time: Measured every 24 hours until Off Advanced Respiratory Support up to 1 yearThe new Severe acute respiratory syndrome coronavirus (SARS-CoV-2) named coronavirus disease 2019 (COVID-19) is currently responsible for a pandemic spread of febrile respiratory infections, responsible for a veritable global health crisis. In adults, several evolutionary patterns are observed: i) a/pauci-symptomatic forms; ii) severe forms immediately linked to rare extensive viral pneumonia; and iii) forms of moderate severity, some of which progress to secondary aggravation (Day 7-Day 10). Children can be affected, but are more rarely symptomatic and severe pediatric forms are exceptional. Like some other coronaviruses (SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV)), these differences in clinical expression could be based on a variability in the immunological response, notably either via inhibition of the type I interferon (IFN-I) response, or on the contrary an immunological dysregulation responsible for a "cytokine storm" associated with the aggravation. Little is known about the impact of these innate immune response abnormalities on the adaptive response. In addition, certain genetic factors predisposing to a state of "hyper-fragility" and certain viral virulence factors could also be predictive of the clinical response. In this context, the main hypothesis is that the virological analysis and the initial biological and immunological profiles are correlated with the initial clinical presentation of COVID-19 infection. In particular, children forms and pauci-symptomatic disease in adults may be linked to a more robust innate immune response, including better production of IFN-I.
Description: Describe the immune response (biological profile in blood samples) of children and adults with COVID-19 infection and correlate it with the initial clinical presentation measurement of the following parameters in blood at time of inclusion: white blood cell count, C-reactive protein, procalcitonin, hepatic and renal functions, ferritin, vitamin C and D, fibrinogen, prothrombin time test and partial thromboplastin time in order to correlate them with the initial clinical presentation.
Measure: Initial biological profile of children and adults with COVID-19 infection Time: Day 0Description: measurement of the following parameters in blood at time of inclusion: interferon alpha and gamma, Tumor necrosis factor (TNF) alpha, interleukins 6 and 10, transcriptomic signature of interferon, lymphocyte phenotyping and monocyte Human Leukocyte Antigen - DR isotype (HLA-DR) expression in order to correlate them with the initial clinical presentation.
Measure: Initial immunological profile of children and adults with COVID-19 infection Time: Day 0Description: Determine whether the initial biological and immunological profiles (see primary outcome measures) are predictive of a secondary worsening (i.e., admission to intensive care unit, and/or increase in NEWS-2 score, and/or increase in oxygen dependence level) of COVID-19 infection
Measure: Clinical worsening Time: Within 21 days following inclusionDescription: measurement of the following parameters in blood at day 7, and at time of worsening: interferon alpha and gamma, TNF alpha, interleukins 6 and 10, transcriptomic signature of interferon, lymphocyte phenotyping and monocyte HLA-DR expression in order to correlate them with with the secondary worsening
Measure: Evolution of the immunological profile of children and adults with COVID-19 Time: Within 21 days following inclusionDescription: Nasopharyngeal swabs SARS-CoV-2 viral loads (copies/mL) measured at day 0 and correlation to the initial clinical presentation
Measure: Nasopharyngeal swabs SARS-CoV-2 viral loads of children and adults with COVID-19 Time: Day 0Description: Serological SARS-CoV-2 results (titers in specific Immunoglobulin G (IgG) antibodies) measured at day 0 and correlation to the initial clinical presentation
Measure: titers in specific Immunoglobulin G (IgG) antibodies of children and adults with COVID-19 Time: Day 0Description: Serological SARS-CoV-2 results (titers in specific Immunoglobulin M (IgM) antibodies) measured at day 0 and correlation to the initial clinical presentation
Measure: titers in specific Immunoglobulin M (IgM) antibodies of children and adults with COVID-19 Time: Day 0Description: Nasopharyngeal swabs SARS-CoV-2 viral loads (copies/mL) measured within 21 days following inclusion, and correlation to the secondary worsening
Measure: Nasopharyngeal swabs SARS-CoV-2 viral loads of children and adults with COVID-19 Time: Within 21 days following inclusionDescription: Serological SARS-CoV-2 results (titers in specific Immunoglobulin G (IgG) antibodies) measured within 21 days following inclusion, and correlation to the secondary worsening
Measure: titers in specific Immunoglobulin G (IgG) antibodies of children and adults with COVID-19 Time: Within 21 days following inclusionDescription: Serological SARS-CoV-2 results (titers in specific Immunoglobulin M (IgM) antibodies) measured within 21 days following inclusion, and correlation to the secondary worsening
Measure: titers in specific Immunoglobulin G (IgM) antibodies of children and adults with COVID-19 Time: Within 21 days following inclusionDescription: Genotyping using the whole exome sequencing technic (by Illumina HiSEQ 2500) in order to correlate with the initial clinical presentation.
Measure: Genetic profile of adults with COVID-19 infection Time: Day 0Description: Genotyping using the whole exome sequencing technic (Illumina HiSEQ 2500) in order to correlate with with the secondary worsening
Measure: Genetic profile of adults with COVID-19 infection Time: Within 21 days following inclusionThe present study aims to assess the determinants of health-related quality of life and patient-centered long-term outcomes among survivors of hospitalization for Covid-19 in Brazil. The investigators will conduct a multicenter prospective cohort study nested in randomized clinical trials (coalition Covid-19 Brazil initiative) originally designed to assess the effects of specific Covid-19 treatments. Adult survivors of hospitalization due to proven or suspected SARS-CoV-2 infection will be followed up for a period of one year by means of structured telephone interviews. The primary outcome is one-year health-related quality of life assessed by the EQ-5D-3L. Secondary outcomes include all-cause mortality, rehospitalizations, return to work or study, physical functional status assessed by the Lawton & Brody Instrumental Activities of Daily Living Scale, need of long-term ventilatory support, symptoms of anxiety and depression assessed by the Hospital Anxiety and Depression Scale, and symptoms of posttraumatic stress disorder assessed by the Impact of Event Scale-revised. Four sets of variables (1-demographic characteristics, 2-pre-morbid state of health, 3-characteristics of acute illness, and 4- specific Covid-19 treatments received) will be assessed as potential risk factors for health-related quality of life and secondary outcomes.
Description: The outcome will be assessed using the Brazilian version of the Euroqol-5D-3L (EQ-5D3L) questionnaire. The utility score derived from the EQ5D-3L ranges from 0 (death) to 1 (perfect health).
Measure: One-year utility score of health-related quality of life Time: The outcome will be assessed 12 months after enrollment.Description: Incidence of all-cause mortality.
Measure: Incidence of all-cause mortality Time: The outcome will be assessed 3, 6, 9 and 12 months after enrollment.Description: Incidence of all-cause rehospitalizations.
Measure: Incidence of rehospitalizations Time: The outcome will be assessed 3, 6, 9 and 12 months after enrollment.Description: Percentage of return to work or study among patients that were working or studying at the moment of hospitalization.
Measure: Percentage of return to work or study Time: The outcome will be assessed 3, 6, 9 and 12 months after enrollment.Description: The outcome will be assessed using the Lawton & Brody Instrumental Activities of Daily Living Scale (the score ranges from 0 to 8, with higher scores indicating less dependence).
Measure: Score of Instrumental Activities of Daily Living Time: The outcome will be assessed 3, 6, 9 and 12 months after enrollment.Description: Percentage of patients requiring oxygen therapy, non-invasive ventilation, or mechanical ventilation.
Measure: Percentage of long-term ventilatory support need Time: The outcome will be assessed 3, 6, 9 and 12 months after enrollment.Description: The outcome will be assessed using the Hospital Anxiety and Depression Scale (anxiety and depression scores range from 0 to 21, with higher scores indicating worse symptoms).
Measure: Symptoms of anxiety and depression Time: The outcome will be assessed 3, 6, 9 and 12 months after enrollment.Description: The outcome will be assessed using the Impact Event Scale-Revised (the score ranges from 0 to 88, with higher scores indicating worse symptoms).
Measure: Symptoms of posttraumatic stress disorder Time: The outcome will be assessed 3, 6, 9 and 12 months after enrollment.Description: The outcome will be assessed using the Brazilian version of the Euroqol-5D-3L (EQ-5D3L) questionnaire. The utility score derived from the EQ5D-3L ranges from 0 (death) to 1 (perfect health).
Measure: Utility score of health-related quality of life at 3, 6, and 9 months Time: The outcome will be assessed 3, 6, and 9 months after enrollment.Description: The outcome will be assessed using the visual analogue scale of the Brazilian version of the Euroqol-5D-3L questionnaire (EQ-VAS; score range from o to 100, with higher scores indicating better self-rated health).
Measure: Score self-rated health Time: The outcome will be assessed 3, 6, 9, and 12 months after enrollment.This is a multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. Otilimab is a human monoclonal anti-GM-CSF antibody that has not previously been tested in participants with severe pulmonary COVID-19 related disease. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the treatment of patients with severe COVID-19 related pulmonary disease. The study population will consist of hospitalized participants with new onset hypoxia requiring significant oxygen support or requiring early invasive mechanical ventilation (less than or equal to [<=] 48 hours before dosing). Participants will be randomized to receive a single intravenous (IV) infusion of otilimab or placebo, in addition to standard of care.
Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 28 Time: Day 28Description: Number of deaths due to all causes will be assessed.
Measure: Number of deaths due to all causes at Day 60 Time: Day 60Description: Time to death due to all causes will be assessed.
Measure: Time to number of deaths due to all causes at Day 60 Time: Day 60Description: Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 7 Time: Day 7Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 14 Time: Day 14Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 42 Time: Day 42Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 60 Time: Day 60Description: Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Time to recovery from respiratory failure Time: Day 28Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 7 Time: Day 7Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 14 Time: Day 14Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 28 Time: Day 28Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 42 Time: Day 42Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 60 Time: Day 60Description: Time will be recorded from dosing to last dependence on supplementary oxygen. Participants are dependent on supplementary oxygen if they are in category 4 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Time to last dependence on supplementary oxygen Time: Day 28Description: For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.
Measure: Proportion of participants admitted to Intensive Care Unit (ICU) Time: Day 28Description: Defined as the time from dosing to when the participant is discharged from the ICU.
Measure: Time to final Intensive Care Unit (ICU) discharge Time: Day 28Description: Time from dosing to when a participant is discharged from the hospital.
Measure: Time to final hospital discharge Time: Day 28Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence, that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other important medical event that may jeopardize the participant or may require medical or surgical treatment to prevent one of the other outcomes listed before.
Measure: Number of participants with Adverse events (AEs) and Serious adverse events (SAEs) Time: Up to Day 60Effective communication is a critical component of managing pandemic outbreaks like COVID-19. This study explores COVID-19 related public knowledge, perceptions, belief in public health recommendations, intent to comply with public health recommendations, trust in information sources and preferred information sources. Participants are invited to include detailed free-text answers to make sure their COVID-19 experiences are heard.
Description: Binary knowledge measures (true/false questions pertaining to COVID-19) each have a corresponding 5-point confidence score, the inverse of which generates a weighting variable. Weighted knowledge scores will be analyzed via a generalized linear mixed-methods effects model with a logistic link function and a random effect for the participant, generating a probability of correct response from 0 to 1.0.
Measure: Knowledge and Confidence in Knowledge of COVID-19 Time: Through study completion, an average of 3 months.Description: Participants are asked, "Do you think that following these CDC recommendations will decrease the spread of COVID-19 in your community?" and select from a 5-point scale, Minimum: 1=certainly not; Maximum: 5 = most certainly.
Measure: Beliefs about the effectiveness of public health recommendations Time: Through study completion, an average of 3 months.Description: Participants are asked, "Will you follow these recommendations?" and select from a 5-point scale, Minimum: 1=certainly not; Maximum: 5 = most certainly.
Measure: Intent to comply with public health recommendations Time: Through study completion, an average of 3 months.Description: Participants are asked, "How likely is it that you will be diagnosed with any of the following diseases over the next year?" and rate their perceived likelihood of diagnosis for Measles, Flu, Lung Cancer, Ebola and COVID-19 on a 5 point scale. Minimum: 1, very unlikely; Maximum: 5, very likely. Participants are asked, "How serious do you think infection with any of the following diseases would be (or is) to your own personal health?" and rate their perceived seriousness of diagnosis for Measles, Flu, Lung Cancer, Ebola and COVID-19 on a 5 point scale. Minimum: 1, Not at all Serious; Maximum: 5, Very Serious
Measure: Perception of Risk of COVID-19 and other health threats Time: Through study completion, an average of 3 months.Description: Participants are asked the extent to which they trust common information sources: The World Health Organization, The U.S. Centers for Disease Control and Prevention, the European Commission, the participant's national government, the participant's local government, and the participant's personal healthcare provider. Participants rate on a 5 point scale. Minimum: 1, Not at all; Maximum: 2, Completely. (As these sources are not recognized in all places, participants may select "Not Applicable" in lieu of ranking.
Measure: Perceptions of trust in common health information sources Time: Through study completion, an average of 3 months.Description: Participants are asked to identify their single most trusted source of news through selection from a pre-generated list or via free-text.
Measure: Single most trusted news source Time: Through study completion, an average of 3 months.Description: Participants are asked if COVID-19 will change how they consume news (y/n)
Measure: Intention to change consumption of news because of COVID-19 (yes/no) Time: Through study completion, an average of 3 months.Description: Participants who answer, "Yes" to Outcome 7 are asked to provide a free-text response to describe how their consumption of news will change.
Measure: For participants who will change their news consumption, in what way will they change? Time: Through study completion, an average of 3 months.Description: Participants are asked to identify all other sources of information via selection from pre-generated menu or free-text.
Measure: Secondary information sources Time: Through study completion, an average of 3 months.Description: Free-text response invited to describe their concerns regarding COVID-19.
Measure: Concerns about COVID-19 Time: Through study completion, an average of 3 months.A rapid oxygen desaturation has observed in patients with COVID-19 which have seriously respiratory failure and most of them have intubated and connected to the mechanical ventilator. Finally, many of them have died during the process. ORF8 and superficial glycoproteins of a novel coronavirus bind to porphyrin on haemoglobin molecules and inhibit heme metabolism in an erythrocyte. However, it is not clarify the effects of the novel coronavirus on mean corpuscular volume (MCV), mean corpuscular of haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC).
Description: The severity of disease can decrease haemoglobin concentration and destroy oxygen transport.
Measure: Relationship between severity of disease and values of erythrocyte indices Time: 5 daysDescription: Detecting of cut-off value of haemoglobine indices can predict severity of the disease
Measure: Sensitivity of haemoglobin concentration on severity of the disease Time: 5 daysThe purpose of this study is to evaluate the safety of administration of plasma containing antibodies to the SARS-CoV-2 virus (i.e., convalescent plasma) and if it is able to prevent disease or lessen the severity of disease in individuals who are at high risk of developing COVID-19 due to a recent exposure. This study will also measure the level of anti-SARS-CoV-2 antibodies in patient's blood after the administration of the convalescent plasma.
Description: Proportion of subjects with grade 3 and 4 adverse events during the study period
Measure: Safety of treatment with high-titer anti-SARS-CoV-2 plasma as assessed by adverse events Time: 28 daysDescription: Descriptive analysis of these outcomes, e.g. disease worsening as defined by hospitalization, need for supplemental oxygenation, respiratory distress, requirement for mechanical ventilation, and death
Measure: Proportion of subjects with disease worsening event Time: 28 daysDescription: Anti-SARS-CoV-2 antibody titer changes
Measure: Pharmacokinetics of anti-SARS-CoV-2 antibodies as defined by changes in antibody titers Time: Up to 28 daysDescription: This will be assessed by the presence or absence of anti-SARS-CoV-2 antibody titers. Antibody titer will be collected one time between 60-120 days.
Measure: Proportion of subjects with a natural antibody response to SARS-CoV-2 infection Time: 60-120 daysThis is a case series of patients with COVID-19 admitted to the largest university hospital in Sao Paulo, Brazil, during the 2020 COVID-19 pandemic. Data will be collected prospectively and retrospectively. The main objective is to describe the characteristics of critically ill patients with COVID-19 and their clinical outcomes, and to identify risk factors associated with survival, to inform clinical decision-making and to guide the strategy to mitigate the epidemic, both within each hospital and ICU and in public health management.
Description: the proportion of patients who survive to ICU discharge or for 28 days in the ICU
Measure: ICU survival at 28 days Time: 28 daysDescription: the proportion of patients who survive to hospital discharge or for 60 days in the hospital
Measure: Hospital survival at 60 days Time: 60 daysDescription: Number of days under invasive ventilatory support
Measure: Duration of mechanical ventilation Time: 28 daysDescription: Proportion of patients who received renal replacement therapy during the ICU stay
Measure: Need for renal replacement therapy Time: 28 daysDescription: percentage of patients who developed complications during the ICU stay: thromboembolic events, ventilator associated pneumonia, secondary infections, cardiovascular complications
Measure: Complications during the ICU stay Time: 28 daysAccording to the data of February 2020, in Turkey with a population of 83.9 million, internet and social media usage percentage to population are 74% and 64% respectively. Although previous researches have investigated the effect of social media on different medical situations, there is no study focused role of social media on patients' behavior and information source during the COVID-19 pandemic. In the present study, it is aimed to reveal the impact of social media on patients' attitudes and information sources during the COVID-19 pandemic.
Description: applying a custom made survey to examine the role of social media and which type of research module is more effective
Measure: the role of social media Time: 1 weekThis trial is designed to determine if the inflammation modulating effect of vagus nerve stimulation can improve pulmonary function and limit progression to ARDS in hospitalized COVID-19 hospitalized patients.
Description: Survival
Measure: Survival without need of mechanical ventilation Time: Day 14 since symptom onsetDescription: WHO Progression Scale
Measure: WHO progression scale ≤ 5 at day 4 since admission. Time: Score on day 4 since admissionDescription: Successful tracheal extubation
Measure: Cumulative incidence of successful tracheal extubation at day 14 since symptom onset. Time: Day 14 since symptom onsetDescription: WHO Progression Scale
Measure: WHO progression scale ≤ 7 at day 4 since admission. Time: Score on day 7 since admissionDescription: Survival
Measure: Survival at day 14 of hospitalization Time: Day 14Description: Duration of hospitalization
Measure: Duration of hospitalization Time: Day 28Description: Time to hospital discharge
Measure: Time to hospital discharge Time: Day 28Hypothesis: low-dose chest computed tomography, has the same accuracy for the diagnosis of pneumonia compared to the routine protocol. In total, 230 patients are planned to be enrolled in the study. Each patient will have 2 studies (routine chest CT and low-dose chest CT) sequentially during one visit to the computed tomography room.
Description: A standardized scale CT1-CT4 will be used. The expected correlation percentage is 90%.
Measure: Evaluate the correlation between standard CT and low-dose CT scans for the detection of community-acquired pneumonia. Time: Upon completion, up to 1 yearDescription: Expected threshold - 10 mm.
Measure: Threshold value of the infiltration zone size detected by low-dose CT scan compared to standard CT scan. Time: Upon completion, up to 1 yearDescription: Expected number - more than two zones.
Measure: Number of infiltration zones of pulmonary parenchyma corresponding to viral pneumonia detected by low-dose CT scan in comparison with standard CT scan. Time: Upon completion, up to 1 yearThe primary objective of the study is to evaluate the efficacy and safety of a single dose of RPH-104 (80 mg) or OKZ (64 mg) compared to placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 15 of the study
Description: Proportion of patients, responded to the study therapy, in each of the treatment groups. The patient can be considered as the therapy responder, in case tocilizumab or sarilumab were not administered and there is an improvement of a clinical status at least by 1 point on a 6-points COVID-19 scale, where 1 point means most favorable outcome, 6 points means most undesirable outcome.
Measure: Proportion of patients, responded to the study therapy, in each of the treatment groups Time: Day 15Description: Changes of patients' clinical status on a 6 points ordinal scale over time
Measure: Changes of patients' clinical status on a 6 points ordinal scale over time Time: from Day 2 until Day 15, Day 29Description: Mortality rate over the follow-up period
Measure: Mortality rate over the follow-up period Time: from Day 1 until Day 29Description: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.
Measure: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration. Time: on screening and then from Day 1 until Day 29Description: Proportion of patients received tocilizumab or sarilumab due to COVID-19
Measure: Proportion of patients received tocilizumab or sarilumab due to COVID-19 Time: from Day 1 until the Day 29Description: Proportion of patients having National Early Warning Score 2 (NEWS2) of ≤ 4 maintained for 2 consecutive days
Measure: Proportion of patients having National Early Warning Score 2 of ≤ 4 maintained for 2 consecutive days Time: from day 3 until day 15Description: Time to a NEWS2 of ≤ 2 maintained for two consecutive days
Measure: Time to a NEWS2 of ≤ 2 maintained for two consecutive days Time: from day 1 until day 15Description: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, CRP, ferritin (if applicable), D-dimer (if applicable)
Measure: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, C-Reactive protein (CRP), ferritin (if applicable), D-dimer (if applicable) Time: Day 2, Day 3, Day5, Day 7, Day 15Description: Mortality during an ICU stay, on days 7, 15, 29 of the study
Measure: Mortality during an ICU stay, on days 7, 15, 29 of the study Time: On Day 7, Day 15, Day 29Description: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days
Measure: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days Time: from Day 2 until Day 15Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period
Measure: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period Time: On Day 1 and from Day 2 until Day 15Description: Duration of ICU stay measured in days
Measure: Duration of ICU stay measured in days Time: from Day 2 until Day 15Description: Changes from baseline (if applicable) in severity of ARDS according to WHO criteria
Measure: Changes from baseline (if applicable) in severity of Acute Respiratory Distress Syndrome (ARDS) according to World Health Organization (WHO) criteria Time: from Day 1 until Day 15Description: Duration of mechanical ventilation and EMO (if applicable) measured in days
Measure: Duration of mechanical ventilation and Extracorporeal Membrane Oxygenation (EMO) (if applicable) measured in days Time: from Day 2 until Day 15Description: Duration of oxygen support (if applicable) measured in days
Measure: Duration of oxygen support (if applicable) measured in days Time: from Day 1 until Day 15Description: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days
Measure: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days Time: from day 3 until day 15Description: Time to a NEWS2 of ≤ 4 maintained for two consecutive days
Measure: Time to a NEWS2 of ≤ 4 maintained for two consecutive days Time: from day 1 until day 15Description: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)
Measure: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable) Time: On Day 1 and from Day 2 until Day 15Description: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)
Measure: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable) Time: from day 1 until day 15Description: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale
Measure: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale Time: from day 1 until day 29Description: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale
Measure: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale Time: from day 1 until day 29Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study
Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study Time: from Day 1 until Day 29Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable
Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable Time: from Day 1 until Day 29Description: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)
Measure: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable) Time: from Day 1 until Day 29The purpose of the study is to design and execute a prospective, longitudinal, descriptive cohort study in a pragmatic clinical practice for adults with symptoms that may be related to COVID-19.
Description: Patient reported change
Measure: Patient reported main complaint Time: 24 hoursDescription: Patient reported change
Measure: Patient reported main complaint Time: 48 hoursDescription: Patient reported change
Measure: Patient reported main complaint Time: 3 monthsDescription: Patient reported change
Measure: Patient reported main complaint Time: 12 monthsDescription: Patient interview notes as written by clinicians.
Measure: Conduct qualitative analyses of data Time: 24 hoursDescription: Patient interview notes as written by clinicians.
Measure: Conduct qualitative analyses of data Time: 48 hoursDescription: Patient interview notes as written by clinicians.
Measure: Conduct qualitative analyses of data Time: 3 monthsDescription: Patient interview notes as written by clinicians.
Measure: Conduct qualitative analyses of data Time: 12 monthsRandomized open label clinical trial carried out at study centers in Sweden, including Karolinska University Hospital Huddinge, S:t Göran Hospital, Danderyd Hospital and Västmanlands Hospital. Patients with COVID-19 who are hospitalized with oxygen therapy are eligible for inclusion. Subjects are randomized to 14 days of inhalation with ciclesonide 360 µg twice daily or to standard of care. Primary outcome is time (in days) of received supplemental oxygen therapy. Key secondary outcome is a composite outcome of death and received invasive mechanical ventilation within 30 days.
Description: Time (in days) of received supplemental oxygen therapy (defined as being alive and discharged from hospital to home or at least 48 h of not receiving oxygen therapy during hospitalization).
Measure: Duration of received supplemental oxygen therapy Time: 30 days after study inclusionDescription: Rate of and time to (in days) received invasive mechanical ventilation or all-cause death
Measure: Invasive mechanical ventilation or all-cause death Time: 30 days after study inclusionDescription: Rate of and time to (in days) death of any cause
Measure: All cause death Time: 30 days after study inclusionDescription: Rate of and time to (in days) received invasive mechanical ventilation
Measure: Invasive mechanical ventilation Time: 30 days after study inclusionDescription: Maximum received oxygen therapy during hospitalization in liters per minute
Measure: Maximum oxygen therapy Time: 30 days after study inclusionDescription: Time (in days) from study inclusion to discharge from hospital.
Measure: Duration of hospitalization Time: 30 days after study inclusionDescription: Level of remaining dyspnea symptoms according to the Modified Medical Research Council Dyspnea Scale
Measure: Remaining dyspnea symptoms Time: 3 and 6 months after inclusion. (Only for patients hospitalized at S:t Goran's Hospital)Oslo University Hospital has initiated an observational study on hospitalised patients with confirmed COVID-19, the infection caused by Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2).
Description: Fatal outcome from COVID-19
Measure: Death Time: From date of randomization until the date of death from any cause assessed up to 3 months.Description: Resolved infection
Measure: Recovery from COVID-19 Time: From date of randomization until the date of recovery from COVID-19 symptoms assessed up to 3 months.Description: Percentage of patients requiring intensive care admission or ventilation
Measure: Progression to ICU care or ventilation Time: 30 daysDescription: The change in(clearance of) viral RNA measured by polymerase chain reaction assay (PCR) test at days 1, 3, 8,14 and 90 days
Measure: Clearance of SARS-CoV-2 from respiratory specimen Time: The number of calendar days from date of PCR positive test (counted as 1 day) in respiratory specimen until date of such test first become negative in the respiratory specimen assessed up to 3 monthsDescription: Cell-mediated and humoral immunity
Measure: Immune response to COVID-19 Time: From date of randomization until the date of clinical follow-up assessed up to 3 months.The purpose of the COVIDNOCHE trial (HFNO versus CPAP Helmet Evaluation in COVID-19 Pneumonia) is to evaluate the comparative effectiveness of standard care non-invasive respiratory support (helmet CPAP versus HFNO) for acute hypoxemic respiratory failure from COVID-19 pneumonia on ventilator-free days (primary outcome) and other clinical outcomes measured up to 90 days.
Description: VFD is the number of days alive and free of mechanical ventilation in the first 28 days after study enrollment. Death before 28 days will be assigned a VFD equal to 0 to penalize non-survival. In cases of repeated intubation and extubation, periods free from invasive ventilation and lasting at least 24 consecutive hours will be calculated and summed. Timing of intubation and extubation will be captured in hours, and the number of hours a patient received invasive ventilation will be used to calculate duration of ventilation.
Measure: Ventilator-Free Days (VFD) Time: 28 daysDescription: Days spent in the ICU and hospital after time of enrollment
Measure: ICU and Hospital Length of Stay Time: 28 daysDescription: Incidence and time to intubation in days after the time of enrollment
Measure: Intubation Time: 28 daysDescription: Incidence of RRT after the time of enrollment
Measure: Renal Replacement Therapy (RRT) Time: 28 daysDescription: Death from any cause during after the time of enrollment
Measure: Mortality Time: 28 days, 90 daysDescription: Changes in Borg Dyspnea Score after time of enrollment
Measure: Dyspnea Time: 1 hourRECOVERY is a randomised trial investigating whether treatment with either Lopinavir-Ritonavir, Hydroxychloroquine, Corticosteroids, Azithromycin or Tocilizumab prevents death in patients with COVID-19.
Description: For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality.
Measure: All-cause mortality Time: Within 28 days after randomisationDescription: To assess the effects of study treatment on number of days stay in hospital
Measure: Duration of hospital stay Time: Within 28 days after randomisationDescription: To assess the effects of study treatment on number of patients who needed ventilation and the number of days it was required
Measure: Need for (and duration of) ventilation Time: Within 28 days after randomisationDescription: To assess the effects of study treatment on number of patients who needed renal replacement therapy
Measure: Need for renal replacement Time: Within 28 days after randomisationAgent Name and Study Duration ArtemiC is a medical spray comprised of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (=Boswellia) (15 mg/ml) and vitamin C (60 mg/ml) in micellar formulation for spray administration. Patients will receive up to 6 mg Artemisinin, 20 mg Curcumin, 15 mg Frankincense and 60 mg vitamin C given daily as an add-on therapy (in addition to standard care) in two divided doses, on Days 1 and 2. Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care. Patient follow-up will last 2 weeks. During this time, patients will be monitored for adverse events. Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy. Placebo, composed of the same solvent but without active ingredients, will be given in the placebo group as add-on therapy, 2 times a day, on Days 1 and 2. Overall rationale A preparation of ArtemiC, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus SARS-CoV-2. It is readily available in light of its status as a food supplement. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed. Leading among these considerations are well established immuno-modulatory activities of the active ingredients as established in vitro and in vivo and published over the years. These activities as apparent, for example, in diminishing activity of TNF alpha and IL-6 levels are acknowledged to be relevant to the pathophysiology processes involved in the progressive form of COVID-19. The active agents have in addition prominent anti-oxidant, anti-inflammatory as well as anti-aggregant and anti-microbial activities. Based on these activities and observations in animal models, together with clinical experience of the separate ingredients and in various combinations in other contexts it is proposed to evaluate their effect in the context of COVID-19. Study Purpose This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19. Methodology 50 adult patients who suffer from COVID-19 infection studied in parallel groups treated with active agent or placebo as add on to standard care. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.
Description: patient will be assessed using a scoring table for changes in clinical signs
Measure: Time to clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of = 2 Maintained for 24 Hours in comparison to routine treatment Time: 24 hoursDescription: Adverse events caused by the study drug will be assessed
Measure: Percentage of participants with definite or probable drug related adverse events Time: 14 daysThe study is a prospective, randomized, controlled investigation designed for comparison of two groups for the reduction of respiratory distress in a CoViD-19 population, using gammaCore Sapphire (nVNS) plus standard of care (active) vs. standard of care alone (SoC), the control group. The gammaCore® (nVNS) treatments will be used acutely and prophylactically. The active and control groups will be diseased and severity matched. The primary objective is to reduce initiation of mechanical ventilation in patients with CoViD-19 compared to the control group. Secondary objectives are to evaluate cytokine trends/prevent cytokine storms, evaluate supplemental oxygen requirements, decrease mortality of CoViD-19 patients and to delay the onset of mechanical ventilation.
Description: measure the change (in hours) between the control group and treatment group
Measure: change in initiation of mechanical ventilation in patients with CoViD-19 compared to the control group. Time: From the time of randomization until the time of initiation of mechanical ventilation, assessed up to day of discharge or death, whichever occurs first, assessed up to 3 monthsDescription: measure the changes in the serum/plasma concentrations of TH1 and TH2-type cytokines
Measure: evaluate cytokine trends Time: From the time of initial blood draw until the time of final blood draw, assessed up to date of mechanical ventilation, death, or discharge from hospital, whichever occurs first,assessed up to 3 monthsDescription: compare the difference in oxygen requirements (liters/min) between the control group and active group for patients admitted to the hospital for CoViD-19.
Measure: evaluate supplemental oxygen requirements Time: From the time of randomization, assessed up to time of mechanical ventilation, day of discharge or death, whichever occurs first,assessed up to 3 monthsDescription: measure the change (in hours) to death between control group and treatment group
Measure: decrease mortality of CoViD-19 patients Time: From the time or randomization until the date of death from any cause, assessed up to day of discharge or death,assessed up to 3 monthsDescription: measure the change (in hours) to time of mechanical ventilation between control group and treatment group
Measure: delay onset of ventilation Time: From the time of randomization until the time of initiation of mechanical ventilation, assessed up to day of discharge or death, whichever occurs first,assessed up to 3 monthsA weekly questionnaire is sent to patients and parents of patients who are vulnerable for infections. Possible symptoms of COVID19 are asked for and use of healthcare services and testing for COVID19. Weekly reports are being send to the national institutions to update advice given to this group.
Description: To describe frequency of cough, fever, diarrhoea, shortness of breath, sore throat, blocked nose, red eyes, headache, joint pain, muscle pain, fatigue, chills, nausea, vomiting, diarrhoea over a year
Measure: To describe COVID19 infection in children/adults who are vulnerable for infection in an outpatients setting Time: 1 yearDescription: Patient/parent reported positive tests for COVID19
Measure: Number of children/adults tested positive for COVID19 Time: 1 yearDescription: Patient/parent reported admissions in hospital because of COVID19
Measure: Number of children/adults admitted in hospital because of COVID19 Time: 1 yearDescription: Patient/parent reported effect of COVID19 on daily activities
Measure: To assess the impact of COVID19 infection on the daily activities of immunosuppressed adults and children Time: 1 yearThe study aims to evaluate the reduction in severity and progression of lung injury with inhaled ibuprofen in patients with severe acute respiratory syndrome due to SARS-CoV-2 virus.
Description: Time to clinical improvement: defined as time from inhaled Ibuprofen first dose to an improvement of three points from the status on a seven-category ordinary scale
Measure: Change in the scale of ordinary COVID results at 7, 14 and 28 days in patients with acute respiratory infection, induced by SARS-CoV-2, treated with inhaled Ibuprofen. Time: 7, 14 and 28 daysDescription: Negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart
Measure: Change to Negativization of the swab to the following treatment points on day 7, day 14, 21 and 28 after treatment with inhaled Ibuprofen. Time: 7, 14 and 28 daysDescription: NEWS2 score 20 points is the maximum and indicates that the patient needs emergent assessment by a clinical team or critical care team and usually transfer to higher level of care.
Measure: Average score of National Early Warning (NEWS2) between days 1, 7, 14 and 28. Time: 1, 7, 14 and 28Description: qSOFA, score for sepsis, a maximum value of 3 indicates high risk qSOFA Scores 2-3 are associated with a 3- to 14-fold increase in in-hospital mortality. Assess for evidence of organ dysfunction with blood testing including serum lactate and calculation of the full SOFA Score. Patients meeting these qSOFA criteria should have infection considered even if it was previously not.
Measure: Average change in quick sepsis-related organ failure assessment score (qSOFA) score between day 1, 7, 14 and 28. Time: 1, 7, 14 and 28 daysAzithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2; ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019.
Description: the number of patients with virological cure
Measure: Number of patients with virological cure Time: 6 monthsThe vital signs are critical in assessing the severity and prognosis of infections, such as Covid-19. The devices used today for measuring the vital signs have to be in physical contact with the patients. There is an apparent risk of transferring infections from one patient to the next (or to healthcare professionals). This project aims to evaluate a new camera-based system for contactless measurement of vital signs as well as an artificial intelligence (AI) predicting hospitalization or death within 30 days. This particular study will evaluate the new system's ability without interfering with standard care of the patient.
Description: Body temperature will be measured with the new camera based method as well as with a conventional ear thermometer. Both measurements will estimate the body temperature in degrees Celsius. The agreement between body temperature estimated with the new method and the reference method will be made using the statistical methods Bland-Altman plots and limits of agreement as the outcome.
Measure: Agreement between the new camera based method and reference standard to estimate body temperature Time: Two minutes between measurementsDescription: Heart rate will be measured with the new camera based method as well as with a conventional apparatus for measuring pulse rate. Both measurements will estimate the heart rate in beats per minute. The agreement between body temperature estimated with the new method and the reference method will be made using the statistical methods Bland-Altman plots and limits of agreement as the outcome.
Measure: Agreement between the new camera based method and reference standard to estimate heart rate Time: Two minutes between measurementsDescription: Blood oxygen saturation will be measured with the new camera based method as well as with a conventional apparatus for measuring blood oxygen saturation. Both measurements will estimate the blood oxygen saturation in percent (ranging from 0-100%). The agreement between blood oxygen saturation estimated with the new method and the reference method will be made using the statistical methods Bland-Altman plots and limits of agreement as the outcome.
Measure: Agreement between the new camera based method and reference standard to estimate blood oxygen saturation Time: Two minutes between measurementsDescription: Systolic blood pressure will be measured with the new camera based method as well as with a conventional apparatus for measuring systolic blood pressure. Both measurements will estimate the systolic blood pressure in mm Hg. The agreement between systolic blood pressure estimated with the new method and the reference method will be made using the statistical methods Bland-Altman plots and limits of agreement as the outcome.
Measure: Agreement between the new camera based method and reference standard to estimate systolic blood pressure Time: Two minutes between measurementsDescription: Diastolic blood pressure will be measured with the new camera based method as well as with a conventional apparatus for measuring diastolic blood pressure. Both measurements will estimate the diastolic blood pressure in mm Hg. The agreement between diastolic blood pressure estimated with the new method and the reference method will be made using the statistical methods Bland-Altman plots and limits of agreement as the outcome.
Measure: Agreement between the new camera based method and reference standard to estimate diastolic blood pressure Time: Two minutes between measurementsDescription: Respiratory rate will be measured with the new camera based method as well as manually using a stethoscope. Both measurements will estimate the respiratory rate in breath per minute. The agreement between respiratory rate estimated with the new method and the reference method will be made using the statistical methods Bland-Altman plots and limits of agreement as the outcome.
Measure: Agreement between the new camera based method and reference standard to estimate respiratory rate Time: Two minutes between measurementsDescription: An artificial intelligence (AI) algorithm will use 75% of patient observations of vital signs for training and the remaining 25% will be used to test the AIs predictive capabilities to predict hospital admission within 30 days. For each patient the AI will produce a probability (0-100%) for hospital admission within 30 days. These probabilities will undergo a receiver operating (ROC) analysis where area under curve (AUC) with 95% confidence interval will be the reported outcome measure.
Measure: Prediction of hospital admission using vital signs estimated using reference standard methods Time: Hospital admission for any cause up until 30 days after inclusionDescription: An artificial intelligence (AI) algorithm will use 75% of patient observations of vital signs for training and the remaining 25% will be used to test the AIs predictive capabilities to predict death within 30 days. For each patient the AI will produce a probability (0-100%) for death within 30 days. These probabilities will undergo a receiver operating (ROC) analysis where area under curve (AUC) with 95% confidence interval will be the reported outcome measure.
Measure: Prediction of death using vital signs estimated using reference standard methods Time: Death for any cause up until 30 days after inclusionDescription: An artificial intelligence (AI) algorithm will use 75% of patient observations of vital signs for training and the remaining 25% will be used to test the AIs predictive capabilities to predict hospital admission within 30 days. For each patient the AI will produce a probability (0-100%) for hospital admission within 30 days. These probabilities will undergo a receiver operating (ROC) analysis where area under curve (AUC) with 95% confidence interval will be the reported outcome measure.
Measure: Prediction of hospital admission using vital signs estimated using the new camera based method Time: Hospital admission for any cause up until 30 days after inclusionDescription: An artificial intelligence (AI) algorithm will use 75% of patient observations of vital signs for training and the remaining 25% will be used to test the AIs predictive capabilities to predict death within 30 days. For each patient the AI will produce a probability (0-100%) for hospitalization within 30 days. These probabilities will undergo a receiver operating (ROC) analysis where area under curve (AUC) with 95% confidence interval will be the reported outcome measure.
Measure: Prediction of death using vital signs estimated using the new camera based method Time: Death for any cause up until 30 days after inclusionDescription: An artificial intelligence (AI) algorithm will use 75% of patient observations of raw camera data for training and raw data from the remaining 25% of patients will be used to test the AIs predictive capabilities to predict hospital admission within 30 days. For each patient the AI will produce a probability (0-100%) for hospital admission within 30 days. These probabilities will undergo a receiver operating (ROC) analysis where area under curve (AUC) with 95% confidence interval will be the reported outcome measure.
Measure: Prediction of hospital admission using raw camera data Time: Hospital admission for any cause up until 30 days after inclusionDescription: An artificial intelligence (AI) algorithm will use 75% of patient observations of raw camera data for training and raw data from the remaining 25% of patients will be used to test the AIs predictive capabilities to predict death within 30 days. For each patient the AI will produce a probability (0-100%) for death within 30 days. These probabilities will undergo a receiver operating (ROC) analysis where area under curve (AUC) with 95% confidence interval will be the reported outcome measure.
Measure: Prediction of death using raw camera data Time: Death for any cause up until 30 days after inclusionIt has been suggested that ibuprofen might be associated with more severe cases of coronavirus infections, based on the observation that severe COVID cases had been exposed to ibuprofen, resulting in a warning by the French authorities. This was attributed to: 1. a suggestion that ibuprofen might upregulate ACE-2 thereby increasing the entrance of COVID-19 into the cells, 2. an analogy with bacterial soft-tissue infections where more severe infections on NSAIDs are attributed to an immune-depressive action of NSAIDs, or to belated treatment because of initial symptom suppression, 3. fever is a natural response to viral infection, and reduces virus activity: antipyretic activity might reduce natural defenses against viruses. However fever reduction in critically ill patients had no effect on survival. However, these assertions are unclear: upregulation of ACEII would increase the risk of infection, not necessarily its severity, and would only apply to the use of NSAIDs before the infection, i.e. chronic exposure. It would be irrelevant to the infection once the patients are infected, i.e., to symptomatic treatment of COVID-19 infection. Anti-inflammatory effect masking the early symptoms of bacterial infections resulting in later antibiotic or other treatment is not applicable: there is no treatment of the virus that might be affected by masking symptoms. Antipyretic effect increasing the risk or the severity of infection would apply equally to all antipyretic agents including paracetamol, which share the same mechanism of action for fever reduction. EMA remains prudent about this assertion In addition, excess reliance on paracetamol while discouraging the use of ibuprofen might increase the risk of hepatic injury from paracetamol overdose. Paracetamol is the prime drug associated with liver injury and transplantation, in voluntary and inadvertent overdose or even at normal doses. This might be increased by COVID-related liver function alterations. It is therefore proposed to conduct a case-control study in a cohort of patients admitted to hospital in France with COVID-19 infection.
Description: Describe medications including ibuprofen used prior to admission associated with worse infection in COVID-19 patients in France. Thanks to a questionnaire created for the study, with 5 questions on existing pathology, drugs administrated symptom onset and when, hospitalisation. Each questions have a multiple choice.
Measure: Describe medications used prior to admission associated with worse infection in COVID-19 patients in France. Time: At inclusion dayDescription: Quantify medications including ibuprofen used prior to admission associated with worse infection in COVID-19 patients in France. Thanks to a questionnaire created for the study, with 5 questions: existing pathology, drugs administrated symptoms onset and when, hospitalisation. Each questions have a multiple choice.
Measure: Quantify medications used prior to admission associated with worse infection in COVID-19 patients in France. Time: At inclusion dayDescription: Describe patient characteristics thanks to the same questionnaire.
Measure: Describe other patient characteristics with worse infection in COVID-19 patients in France. Time: At inclusion dayDescription: Quantify patient characteristics thanks to the same questionnaire.
Measure: Quantify other patient characteristics with worse infection in COVID-19 patients in France. Time: At inclusion dayThe Malaysian COVID-19 Anosmia Study is a nationwide multicentre observational study to investigate the prevalence and characteristics of olfactory and gustatory/taste disturbances in COVID-19 infection in Malaysia, and to evaluate the predictive value of screening for these symptoms in COVID-19 infection. This study consists of two phases: the first phase is a cross-sectional study and the second phase is a case-control study. The case-control study is described here (the cross-sectional study is described in a separate ClinicalTrials.gov record).
Description: In the patient-reported online questionnaire, subjects will be asked regarding whether they experienced symptoms of olfactory and/or taste disturbances
Measure: Presence or absence of olfactory and taste disturbances in study participants Time: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infectionDescription: The relationship between case & control status and each exposure variable will be estimated by odds ratios and their 95% confidence intervals using conditional logistic regression models.
Measure: Adjusted odds ratio of olfactory & taste disturbances in COVID-19 infection Time: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked regarding other symptoms they experienced when they were diagnosed with COVID-19/within the past 2 weeks of answering the questionnaire (e.g. headache, nasal congestion, fever, chills, cough, dyspnoea, gastrointestinal symptoms, eye & ear symptoms)
Measure: Clinical manifestations of study participants Time: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked regarding their pre-existing health conditions (for example, obesity, diabetes, hypertension, cardiac conditions, previous head trauma, chronic rhinosinusitis, etc.)
Measure: Other pre-existing health conditions Time: BaselineDescription: PPV reflects the probability that the presence of olfactory and taste disturbances will have a positive diagnosis of COVID-19. This is derived from dividing the number of patients with olfactory & taste disturbances with COVID-19 infection over the total number of patients with olfactory and taste disturbances, and multiplying by 100%
Measure: Positive predictive value (PPV) of olfactory and taste disturbances in predicting diagnosis of COVID-19 infection Time: BaselineDescription: NPV reflects the probability that the absence of olfactory and taste disturbances will have a negative diagnosis of COVID-19. This is derived from dividing the number of patients without olfactory & taste disturbances and without COVID-19 infection over the total number of patients with no olfactory and taste disturbances, and multiplying by 100%
Measure: Negative predictive value (NPV) of olfactory and taste disturbances in predicting absence of COVID-19 infection Time: BaselineDescription: The percentage of true positives, i.e. the proportion of patients with olfactory and taste disorders with COVID-19 infection. This can be calculated by dividing the number of subjects with olfactory & taste disturbances who have COVID-19 infection with the number of patients with olfactory & taste disturbances, and multiplying by 100%
Measure: Sensitivity of olfactory and taste disturbances in predicting COVID-19 infection Time: BaselineDescription: The percentage of true negatives, i.e. the proportion of patients without olfactory and taste disorders who do not have COVID-19 infection. This can be calculated by dividing the number of subjects without olfactory & taste disturbances who do not have COVID-19 infection with the number of patients without olfactory & taste disturbances, and multiplying by 100%
Measure: Specificity of olfactory and taste disturbances in predicting COVID-19 infection Time: BaselineThe effective medical treatment against COVID-19 infection is still unknown. Chloroquine phosphate is a well-known antimalarial drug which has been on the market for many years. Recently, in vitro study shown that Chloroquine is effective at both entry and at post-entry stages of the COVID-19 infection of Vero E6 cells with promising results. Chloroquine is also an immune-modifier and could distribute to the whole body including lung. Also, chloroquine is cheap and safe, and could be a promising agent against COVID-19 infection. However, only hydroxychloroquine (HCQ) with the extra hydroxyl group is available in Taiwan. Therefore, hydroxychloroquine instead become the best choice for the treatment candidate, since it shows higher in vitro potency (EC50) against COVID-19 with lower toxicity while retaining the original effect which compared with chloroquine.
Description: To evaluate the efficacy of HCQ, with respect to the time to negatively RT-PCR assessments in COVID-19 patients.
Measure: Time to negatively RT-PCR Time: 14 daysDescription: To evaluate the efficacy of HCQ in the aspect of virologic assessments in COVID-19 patients
Measure: Virologic assessment Time: 14 daysDescription: To evaluate the safety and tolerability of HCQ
Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Time: 28 daysThe purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Organicell Flow for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.
Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician
Measure: Incidence of any infusion associated adverse events Time: 60 DaysDescription: Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Measure: Incidence of Severe Adverse Events Time: 60 DaysDescription: Measured at day 60 or at hospital discharge, whichever comes first.
Measure: All Cause Mortality Time: 60 DaysDescription: Number of participants that are alive at 60 days post first infusion follow up
Measure: Survival Rate Time: 60 DaysDescription: Measure IL-6, IL-2, TNF-alpha from serum of blood samples
Measure: Cytokine Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab
Measure: D-dimer Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: CRP from serum of blood samples
Measure: C-reactive protein Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: Viral load by real time RT methodology using blood samples or nose / throat swab
Measure: Quantification of the COVID-19 Time: Day 0, Day 4, Day 8Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.
Measure: Improved Organ Failure Time: Day 30Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.
Measure: Chest Imaging Changes Time: Day o, Day 30We have to be aware of the challenge and concerns brought by 2019-nCoV to our healthcare workers. Front-line healthcare workers can become infected in the management of patients with COVID-19; the high viral load in the atmosphere, and infected medical equipment are sources for the spread of SARS-CoV-2. If prevention and control measures are not in place, these healthcare workers are at great risk of infection and become the inadvertent carriers to patients who are in hospital for other diseases. Nowadays a question that has not yet been clarified by science has been arises: is hydroxychloroquine associated with zinc effective as a prophylaxis for asymptomatic healthcare workers involved in the treatment of suspected or confirmed cases of COVID-19?
Description: Proportion of participants in whom there was a clinical finding of COVID-19, defined as the occurrence of signs and symptoms suggestive of this disease, corroborated by the detection of SARS-CoV-2 through specific examination (RT-PCR) or by serology for antibodies specific (IgM and IgG).
Measure: Proportion of participants in whom there was a clinical finding of COVID-19. Time: Day 50Description: Number of symptomatic COVID-19 infections.
Measure: Symptomatic COVID-19 infections. Time: Day 50Description: Proportion of Healthcare Workers who developed mild, moderate, or severe forms of COVID-19.
Measure: Healthcare Workers who developed mild, moderate, or severe forms of COVID-19. Time: Day 50Description: Measurement of the QT interval through electrocardiogram evaluation.
Measure: Measurement of the QT interval. Time: Day 0, day 15 and day 50Description: Proportion of Healthcare Workers who evolved with widening of the corrected QT interval or with changes in heart rate on the ECG.
Measure: Widening of the corrected QT interval or with changes in heart rate on the ECG. Time: Day 15 and day 50.Description: Comparison of baseline (visit 1) and final (visit 4) values of hematological and biochemical parameters.
Measure: Comparison of hematological and biochemical parameters. Time: Day 50Description: Proportion of occurrence of adverse events reported by Healthcare Workers or verified by the attending physician, or even observed in laboratory tests.
Measure: Occurrence of adverse events. Time: Day 50Since December 2019, the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic has spread around the world. The people most exposed to this virus remain the healthcare personnel who are on the front line in the fight against this pandemic. Due to the delayed nature of the pandemic in Reunion island and its insular geographical situation, the study of the voluntary medical personnel will allow the investigators to establish a longitudinal follow-up of the anomalies of the lipidic balance in relation to the exposure to the SARS-Cov virus. 2. During bacterial infections, the lipid profiles are profoundly modified with very significant reductions in plasma cholesterol levels, LDL-C but especially HDL-C whose concentrations are particularly low. Lipid profiles are altered during viral infections, for example, the severity of dengue is inversely correlated with total cholesterol and LDL-C but not with HDL-C levels, according to a recent meta-analysis. The hepatitis C virus circulates in serum linked to lipoproteins rich in triglycerides and HDL can facilitate its entry into cells via Scavenger receptor class B type 1 (SRB1). Likewise, it has been shown that apoA1 can bind to the dengue virus and increase its infectivity by promoting its entry into cells, also via SRB1. At the moment, nothing is known about the lipid profiles in subjects with SARS-CoV-2. The investigator hypothesize that a drop in plasma HDL-C levels and a change in their size during infection could justify future therapeutic approaches aimed at supplementing the subjects most at risk of pulmonary complications. In a model of Pseudomonas aeruginosa pneumonia in mice, investigators have shown that the injection of reconstituted HDL allowed to limit the pulmonary inflammation and the deleterious consequences of the infection. The investigator propose to study not only the lipid profiles in subjects who are infected with SARS-CoV-2 but also the polymorphisms of genes involved in the regulation of lipoprotein levels like that of Cholesterol Ester-Transfer Protein (CETP) depending on the developed forms, symptomatic or not.
Description: lipid profile
Measure: Change of lipid profile during exposure to SARS-Cov-2 Time: at the end of the study, maximum 1 yearDescription: HDL-cholesterol size
Measure: HDL-cholesterol size Time: at the end of the study, maximum 1 yearDescription: circulating plasma cytokine levels
Measure: circulating plasma cytokine levels Time: at the end of the study, maximum 1 yearDescription: ACE2 gene polymorphisms
Measure: ACE2 gene polymorphisms Time: at the end of the study, maximum 1 yearPilot study of tolerability and efficacy of transfusion of 200mL of convalescent plasma in patients with COVID-19 respiratory disease.
Description: For intubated patients improvement in PaO2/FiO2
Measure: Improvement in respiratory disease Time: day 1 post transfusionDescription: For intubated patients improvement in PaO2/FiO2
Measure: Improvement in respiratory disease Time: day 3 post transfusionDescription: For intubated patients improvement in PaO2/FiO2
Measure: Improvement in respiratory disease Time: day 5 post transfusionDescription: For intubated patients improvement in PaO2/FiO2
Measure: Improvement in respiratory disease Time: day 7 post transfusionDescription: For intubated patients improvement in PaO2/FiO2
Measure: Improvement in respiratory disease Time: day 14 post transfusionDescription: For intubated patients improvement in PaO2/FiO2
Measure: Improvement in respiratory disease Time: day 28 post transfusionDescription: For non intubated patients time to intubation post transfusion
Measure: Improvement in respiratory disease Time: 7 daysDescription: ICU length of stay
Measure: ICU Length of Stay Time: 28 daysDescription: Hospital length of stay
Measure: Length of Stay Time: 28 daysDescription: Duration of time on ventilator
Measure: Ventilator days Time: 28Description: Adverse transfusion events
Measure: Tolerability of convalescent plasma Time: During transfusion, 1 day post-transfusionDescription: Improvement in Chest X Ray
Measure: Radiographic improvement Time: 3 days post transfusionDescription: Improvement in Chest X Ray
Measure: Radiographic improvement Time: 28 days post transfusionIn December 2019, the first patients infected with the 2019 novel coronavirus (2019-nCoV) were diagnosed in Wuhan. The clinical presentation and course of Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2) infection is poorly understood in older patients and is certainly different from the general population. This project is designed to better understand and to determine clinical, biological and radiological markers of poor adverse outcomes in hospitalized older patients diagnosed with COVID-19.
Description: We measure functional score of comorbidities
Measure: To evaluate the relative contributions of comorbidities on intra-hospitalized death Time: 1 monthDescription: We measure Functional Independence Measure scale
Measure: To evaluate the relative contributions of functional characteristics on intra-hospitalized death Time: 1 monthDescription: We describe the role fo geriatric syndrome such as delirium, falls
Measure: To explore specific clinical profiles that may influence COVID-19 disease outcomes in the elderly based on geriatrics syndromes Time: 1 monthIn December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. The aim of the study is to investigate the influence of extracorporeal cytokine adsorption on interleukin-6-levels and time to successful ECMO explantation under controlled conditions in patients with particularly severe COVID-19 disease requiring extracorporeal membrane oxygenation.
Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)
Measure: IL-6 reduction by 75% or more after 72 hours as compared to the baseline measurement Time: 72 hoursDescription: time to successful ECMO-explantation within 30 days after randomization
Measure: time to successful ECMO-explantation Time: 30 daysDescription: Ventilator free days (VFD) in the first 30 days after randomization, where invasive mechanical ventilation (IMV), non-invasive ventilation (NIV) and ECMO are defined as ventilator days. VFD=0, if the patient dies in the first 30 days after randomization
Measure: Ventilator free days (VFD) Time: 30 daysDescription: Time to extubation from ventilation and explantation from ECMO. Death under ventilation and/or ECMO will be analyzed as a competing event. The time will be censored at the time of last visit for surviving patients under ventilation and/or ECMO.
Measure: Time to extubation from ventilation and explantation from ECMO Time: 30 daysDescription: Overall survival time, defined as time from randomization to death. The time will be censored at the time of last visit for surviving patients.
Measure: Overall survival time Time: 30 daysDescription: Days on intensive care unit (ICU)
Measure: Days on intensive care unit (ICU) Time: 30 daysDescription: Vasopressor dosage of adrenaline, noradrenaline, vasopressin, and dobutamine at 24, 48,72 h
Measure: Vasopressor dosage Time: 24, 48, 72 hoursDescription: Total fluid[ml] substitution and fluid balance [ml] at 24, 48, 72 h
Measure: Fluid substitution and fluid balance Time: 24, 48, 72 hoursDescription: Serum lactate at 24, 48, 72 h
Measure: Serum lactate Time: 24, 48, 72 hoursDescription: Urine output at 24, 48, 72 h
Measure: Urine output Time: 24, 48, 72 hoursDescription: Willebrand factor at 24, 48, 72 h
Measure: Willebrand factor Time: 24, 48, 72 hoursDescription: d-dimers at 24, 48, 72 h
Measure: d-dimers Time: 24, 48, 72 hoursDescription: interleukin-6 levels at 24, 48, 72 h
Measure: interleukin-6 levels Time: 24, 48, 72 hoursDescription: Sequential Organ Failure Assessment Score at 24, 48, 72 h (values from 6 to 24, where the higher values explain higher disease severity)
Measure: SOFA-Score Time: 24, 48, 72 hoursDescription: serious complications or malfunctions related to the CytoSorb device
Measure: serious adverse device effects Time: 30 daysDescription: unintended air in the ECMO system during operation of the device
Measure: adverse event of special interest: air in the ECMO system Time: 30 daysDescription: unintended blood-clotting in the ECMO system during operation of the device
Measure: adverse event of special interest: blood-clotting in the ECMO system Time: 30 daysDescription: major bleeding events
Measure: adverse event of special interest: bleeding complications Time: 30 daysNasal High Flow oxygen therapy (NHF) is commonly used as first line ventilatory support in patients with acute hypoxemic respiratory failure (AHRF). It's use has been initially limited in Covid-19 patients presenting with AHRF. The aim of the study is to describe the use of NHF in Covid-19-related AHRF and report the changes in the respiratory-oxygenation index (termed ROX index) over time in these patients.
Description: values of ROX index during ICU stay
Measure: Changes in ROX index Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: percentage of patients requiring intubation
Measure: NHF failure Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: level of flow used with NHF
Measure: NHF flow Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: level of inspired fraction in oxygen used with NHF
Measure: NHF inspired fraction in oxygen Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: level of pulse oxymetry during NHF therapy
Measure: oxygenation Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: respiratory rate during NHF therapy
Measure: respiratory status Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: defining the values of ROX index associated with intubation
Measure: prediction of intubation Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsDescription: defining the values of ROX index associated with NHF success (no intubation required)
Measure: prediction of NHF success Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 monthsIt is clear now that SARS-CoV-2 could use angiotensin-converting enzyme 2 (ACE2), the same receptor as SARS-CoV Transmembrane protease serine type 2 (TMPRSS2), a protease belonging to the type II transmembrane serine protease family, cleaves the coronavirus spike protein Serine proteases are inhibited by a diverse group of inhibitors, The best-studied serpins are antithrombin and alpha 1-antitrypsin
Description: Time to clinical improvement, from the point of randomization to two-point improvement on a seven-point ordinal scale or discharged alive from hospital, whichever comes first. Ordinal Scale - 1, Ambulatory with normal activities; 2, Ambulatory with limitation of normal activities; 3, not requiring supplemental oxygen; 4, requiring supplemental oxygen by mask or nasal prongs; 5, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, requiring ECMO, invasive mechanical ventilation, or both; and 7, death
Measure: clinical improvement Time: we will follow the patient daily starting from the day 0 which is the first day of giving drug for 3 weeks or till clinical improvement and discharge from the hospital or till death whichever comes first.Demographics of pregnant COVID persons under investigation and those who were positive from March-May 2020. Looking at demographics including age, socio-economic status and pregnancy outcomes in these groups.
Description: increased risk of preterm birth, preeclampsia, etc.
Measure: Pregnancy Outcome Time: through study completion, approximately 1 yearThe aim of this study is to reduce COVID-19 related pulmonary complications in adult patients undergoing all types of elective or emergency surgery in a COVID-19 exposed environment. A Trial in Low and Middle Income Countries (LMICs) and A Trial in High Income Countries (HICs)
Description: The primary outcome is any one of the following COVID-19 specific, inpatient, postoperative pulmonary complications: Pneumonia Acute respiratory distress syndrome (ARDS) Death
Measure: Pneumonia free survival; acute respiratory distress syndrome (ARDS) free survival; or death Time: From randomisation until discharge from hospital, average less than 30 daysDescription: Pneumonia will be presented and analysed separately as a secondary outcome measure as well as within the composite primary outcome measure.
Measure: Rate of Pneumonia Time: From randomisation until discharge from hospital, average less than 30 daysDescription: ARDs will be presented and analysed separately as a secondary outcome measure
Measure: Rate of ARDs Time: From randomisation until discharge from hospital, average less than 30 daysDescription: Death will be presented and analysed separately as a secondary outcome measure
Measure: Death rate Time: From randomisation until discharge from hospital, average less than 30 daysDescription: Unexpected inability to extubate and wean patient from ventilation after general anaesthesia, or reintubation and ventilation by 30 days after surgery
Measure: Rate of unexpected ventilation Time: From operation until 30 days post operationDescription: Postoperative diagnosis of proven COVID-19 pulmonary complications
Measure: COVID-19 pulmonary complications Time: 30 days post-surgeryDescription: Overall SARS-CoV-2 infected rate (symptomatic and/or asymptomatic)
Measure: Overall SARS-CoV-2 infected rate Time: 30 days post-surgeryDescription: Duration of hospital stay (including time spent in intensive care, time ventilated)
Measure: Duration of hospital stay Time: 30 days post-surgeryDescription: Pulmonary function in keeping with the World Health Organisation (WHO) Solidarity Trial outcome scale
Measure: Pulmonary function Time: 30 days post-surgeryIntroduction There are currently no treatments with demonstrated efficacy for COVID-19 infection. Epidemiological evidence points to the existence of intrinsic protection factors which make young persons and women more resistant to the infection, whereas older patients with multiple illnesses, above all with heart disease, are at greatest risk. This trial proposes treatment initiated in the early stages of the disease, when clinical worsening is most likely, with intravenous Oxytocin (OT), an endogenous hormone currently safely used in clinical practice. The selection of this molecule is based on numerous experimental and clinical observations, which show its activity in modulating resistance to pathogens, in mitigating overall cardiovascular risk, and in acting on the production of Nitric Oxide (ON) in the lungs, which is emerging as a key therapeutic factor for the improvement of respiratory function in patients with SARS-COVID 19. Finally, OT is physiologically produced by the human body, especially in the female sex and in the age ranges that coincide with most resistant patients. In routine clinical practice, OT exhibits an excellent therapeutic index, in absence of significant adverse effects. Primary aim To assess the effects of Oxytocin in addition to standard therapy, with respect to Standard of Care (SoC), in reducing the number of patients who enter a critical stage Secondary aim To describe: - Mortality 28 days after randomization - Time to mechanical ventilation during the study - Duration of dependency on oxygen supply - Length of stay - Temporal trend of clinical improvement (7-category ordinal scale) - Safety analysis
Description: Proportion of cases who during 14 days exhibit one of the following conditions (the most severe): respiratory failure that requires mechanical ventilation organ failure that requires intensive care monitoring and treatment death
Measure: Proportion of cases who during 14 exhibit one of the following conditions Time: 14 daysDescription: Mortality 28 days after randomization
Measure: Mortality 28 days after randomization Time: 28 daysCoronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. At this time, there are no specific vaccines or treatments for COVID-19. However, there are many ongoing clinical trials evaluating potential treatments Drugs used to treat malaria infection has shown to be beneficial for many other diseases, including viral infections. In this Clinical trial, Investigators will evaluate the effect of Artemisinin / Artesunate on morbidity of COVID-19 patients in decreasing the course of the disease and viral load in symptomatic stable positive swab COVID-19 patients. Investigators are hypothesizing that due to the antiviral properties of this drug it will help as a treatment for the COVID -19 patients. In improving their condition and clearing the virus load,
Description: absence of the virus shedding evidenced by negative swabs
Measure: length of stay in hospital Time: within the first 6 days interventionDescription: reduction of morbidity and mortality
Measure: number of ICU admission Time: 14 daysDescription: finding the time that the symptoms disappear
Measure: resolution of symptoms Time: 6 days - 10 dayMolecular testing (e.g PCR) of respiratory tract samples is the recommended method for the identification and laboratory confirmation of COVID-19 cases. Recent evidence reported that the diagnostic accuracy of many of the available RT-PCR tests for detecting SARS-CoV2 may be lower than optimal. Of course, the economical and clinical implications of diagnostic errors are of foremost significance and in case of infectious outbreaks, namely pandemics, the repercussions are amplified. False positives and false-negative results may jeopardize the health of a single patient and may affect the efficacy of containment of the outbreak and of public health policies. In particular, false-negative results contribute to the ongoing of the infection causing further spread of the virus within the community, masking also other potentially infected people.
Description: assess if inpatients who presented with pneumonia but had a negative test for Covid-19 are positive at the serology for SARS-CoV-2.
Measure: Serology Time: 3 weeksDescription: to find if the combination of CT scan and serology could help us in the identification of those patients who were initially negative at laboratory testing alone.
Measure: Efficacy of CT scan and Serology Time: 3 weeksDescription: the efficacy of different pharmaceutical treatments against Covid-19
Measure: Efficacy of different pharmaceutical treatments Time: 3 weeksThe "COVIDOR" epidemiological study. Our study would be the first at the community level in Orleans Métropole, aiming to determine the link between a positive IgM level on the serological test and a healthy carrier of covid-19 in agents in contact with the public. It would provide epidemiological surveillance of anti-covid-19 immunity in the community
Description: Covid-19 attack rate by measuring the frequency of anti-covid-19 IgM in each of the territorial structures
Measure: o study the prevalence of Covid-19 infection, coronavirus (SARS coronavirus-2) in territorial agents in the 3 structures Department, 45 and CDG Orleans Metropolitan Time: 15 minutesDescription: Search for a correlation of covid-19 immunity based on the officer's position, if he is in contact with the public.
Measure: Determine if there is a relationship between the profession carried out by the agents of the territorial community of Orleans metropolis, the Department, the Loiret Management Center and contamination by covid-19 Time: average 1 yearProspective nationwide cohort study of pregnant women enrolled early in gestation and followed for Covid-19 exposure and infection, with follow up of obstetrical outcomes and infant development through the first year of life.
Description: Determine the prevalence of SARS-CoV-2 infection throughout pregnancy in women whose pregnancy was documented at a SART member clinic in the United States between November 2019-December 2020. The investigators will use patient-reported information on infection symptoms as well as serological testing to capture both symptomatic and asymptomatic infections. Deliverable: By instituting the first prospectively tracked U.S.-based pregnancy cohort with precisely timed conception, the investigators will provide foundational, urgent data regarding the epidemiology of SARS-CoV-2 infection at varying gestational ages, across the real-time evolution of the COVID-19 pandemic and in the setting of various public health measures to reduce infection spread.
Measure: Prevalence of SARS-CoV-2 infection throughout pregnancy in women Time: Up to 9 monthsDescription: Determine the incidence of SARS-CoV-2 infection throughout pregnancy in women whose pregnancy was documented at a SART member clinic in the United States between November 2019-December 2020. The investigators will use patient-reported information on infection symptoms as well as serological testing to capture both symptomatic and asymptomatic infections. Deliverable: By instituting the first prospectively tracked U.S.-based pregnancy cohort with precisely timed conception, the investigators will provide foundational, urgent data regarding the epidemiology of SARS-CoV-2 infection at varying gestational ages, across the real-time evolution of the COVID-19 pandemic and in the setting of various public health measures to reduce infection spread.
Measure: Incidence of SARS-CoV-2 infection throughout pregnancy in women Time: Up to 9 monthsDescription: Determine risk ratios of adverse obstetric outcomes in women infected with SARS-CoV-2 during early pregnancy onward compared to non-infected pregnant women. The investigators will focus on timing of infection (gestational month) and extent of COVID-19 symptoms as potential predictors of risk. Deliverable: The investigators will provide critical information about the maternal and fetal implications of SARS-CoV-2 infection at specific time points in pregnancy, compared to non-exposed pregnancies, and enable evidence-based obstetric surveillance protocols.
Measure: Risk ratios of adverse obstetric in women infect with SARS-CoV-2 during early pregnancy onward compared to non-infected pregnant women Time: Up to 9 monthsDescription: Determine risk ratios of adverse neonatal outcomes in women infected with SARS-CoV-2 during early pregnancy onward compared to non-infected pregnant women. The investigators will focus on timing of infection (gestational month) and extent of COVID-19 symptoms as potential predictors of risk. Deliverable: The investigators will provide critical information about the maternal and fetal implications of SARS-CoV-2 infection at specific time points in pregnancy, compared to non-exposed pregnancies, and enable evidence-based obstetric surveillance protocols.
Measure: Risk ratios of adverse neonatal outcomes in women infected with SARS-CoV-2 during early pregnancy onward compared to non-infected pregnant women Time: Up to 1.5 yearsDescription: Identify clinical, behavioral and sociodemographic determinants that predict risk of (a) maternal infection during pregnancy and (b) severe infection symptomatology (hospitalization, ICU admission). Deliverable: The investigators will provide novel findings that identify high-risk groups warranting more aggressive social avoidance measures during pregnancy.
Measure: Clinical, behavioral, and sociodemographic determinants Time: Up to 27 monthsCOVID-19 has adversely affected the healthcare system across the world. The world was not prepared for global outbreak of infectious diseases. The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is enabling researchers worldwide to acquire a large amount of clinical data regarding coronavirus disease (COVID-19). The COVID-19 infection severely affects the respiratory system in the critical cases and results in mortalities. The affected people experience a dry cough, fever, breathing problems, diarrhea, muscle pain, and sore throat. Besides that, some of the evidence from Italy, South Korea, China, and Spain suggest that the COVID-19 cases also lose their senses of smell and taste resulting in alterations in those patients. The objective of this proposed study is to determine whether COVID-19 cases have Olfactory and gustatory dysfunctions as a hallmark indicator and can be used as diagnostic tools for the isolation of suspected people. Investigators are presenting a prospective proportional case-control study that is conducted to investigate the COVID-19 cases with anosmia and /or Ageusia in a university hospital in Riyadh, Saudi Arabia. The sample size of this case series would be 250 cases of suspected COVID-19 patients. The cases included in the study are analyzed prospectively to determine if the cases had a history of anosmia and /or Ageusia, and then tested for the alteration of these senses through a panel of standardized odors/taste strips. That is looked at statistically allowing us to confirm the proposed effectiveness of these tests as a diagnostic tool.
Description: to how extent alteration of smell and taste senses is related to covid19 status
Measure: correlation of anosmia and ageusia to covid19 positive patients Time: from 1/06/2020 to 31/12/2020Description: to determine the range of sense affection ranging from total loss to mild form
Measure: objective assessment of severity of smell and taste senses alterations in covid19 patients Time: from 1/06/2020 to 31/12/2020the retrospective observation study, the first line to care CAVID-19
Description: The isolated person and first-line care person who taking JGF
Measure: the number confirmed COVID-19 cases Time: 8 weeksDescription: The isolated person and first-line care person who taking JGF
Measure: The person with COVID-19 like symptoms Time: 8 weeksDescription: The isolated person and first-line care person who taking JGF
Measure: The improving rate of COVID-19 like symptoms Time: 8 weeksDescription: The isolated person and first-line care person who taking JGF
Measure: The satisfaction% to taking JGF Time: 8 weeksTo demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 22. Respiratory failure is defined as non-invasive ventilation or high-flow oxygen, intubation and mechanical ventilation, or ventilation with additional organ support (e.g., pressors, RRT, ECMO).
Description: To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 29. Respiratory failure is defined as endotracheal intubation and mechanical ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, noninvasive positive pressure ventilation, clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision making is driven solely by resource limitation
Measure: Proportion of subjects that are alive without respiratory failure at Day 29. Time: Day 29Description: Improvement on the WHO Ordinal Scale for Clinical Improvement (8-point ordinal scale)
Measure: WHO clinical Improvement Time: Day15 Day 22 and Day 29Description: Proportion of subjects with normalization of fever and oxygen saturation through
Measure: Normalization of Fever and Oxygen Time: Day 15, Day 22, and Day 29Description: Percentage of subjects discharged from hospital
Measure: Discharge from Hospital Time: Day 15 and Day 22Description: Proportion of patients alive and free of respiratory failure
Measure: Patients alive and free of respiratory failure Time: Day 15, and Day 22Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused mass mortality in the last 3 months that necessitates urgent development of new therapeutical agents. So far there is no effective anti-viral drug to reduce viral load that has critical importance to prevent progress into severe viral pneumonia and systemic hyper inflammation state. This project is to offer a biologic agent based on T cell derived exosomes. This is a novel approach using our proprietary protocols for drug development. This clinical trial is to test the safety and efficacy of this new agent following targeted delivery by metered dose inhaler. The project have received proper approvals from the Turkish Ministry of Health and Erciyes University, Kayseri Turkey. Turk-Patent Application Number: PCT/TR2020/050302
Description: Safety Assessment
Measure: Adverse reaction (AE) and severe AE (SAE) Time: 28 daysDescription: Time to Clinical Recovery (TTCR)
Measure: Efficacy Assessment Time: 28 daysDescription: Efficacy Assessment
Measure: The Rate of Recovery Without Mechanical Ventilator Time: 28 daysCombination Therapy with Isotretinoin and Tamoxifen may provide Complete Protection against Severe Acute Respiratory Syndrome Coronavirus Abstract: The COVID-19 pandemic caused by SARS-COV-2 has infected over 2,000,000 people causing over 150,000 deaths.Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 and for which there are currently no approved treatments.The principal investigator reported according to previous research data that combination therapy with Isotretinoin and tamoxifen may be provide Complete Protection against Severe Acute Respiratory Syndrome Coronavirus, ACE2-expressing cells can act as home cells and are prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication. A study demonestrated that patients with hypertension and diabetes mellitus may be at higher risk of SARS-CoV-2 infection, as these patients are often treated with ACE inhibitors (ACEIs) or angiotensin II type-I receptor blockers (ARBs), which have been previously suggested to increase ACE2 expression currently being investigated in clinical trials for treating COVID-19 (chloroquine, thalidomide, methylprednisolone, losartan, lopinavir and ritonavir, from clinicaltrials.gov), none of which was found to significantly alter ACE2 expression (P>0.1) Moreover, another study demonstrated that isotretinoin is a Potential papain like protease (PLpro) inhibitors which is a protein encoded by SARS-CoV-2 genes and considered one of the proteins that should be targeted in COVID-19 treatment by performing target-based virtual ligand screening. As Investigators discussed before in their previous clinical trial (NCT04353180) that Isotretinoin is the strongest down-regulator of ACE2. and the principal investigator expects that Isotretinoin can inhibit or downrgulat ACE2 by direct interaction and binding with the transmembrane ACE2, Suggesting its therapeutic potential in preventing the entry of COVID 2019 to the host cell. The second combined drug is tamoxifen, A study demonstrated that tamoxifen causes redistribution of weak base chemotherapeutics from acidic organelles to the nucleus in drug-resistant cells. Agents that disrupt organelle acidification (e.g., monensin, bafilomycin A1) cause a similar redistribution. Measurement of cellular pH in several cell lines reveals that tamoxifen inhibits acidification of endosomes and lysosomes without affecting cytoplasmic pH, Tamoxifen decreased the rate of vesicular transport though the recycling and secretory pathways. Organellar acidification is required for many cellular functions, and its disruption could account for many of the side effects of tamoxifen. A sudy demonstrated that the phagocytosis is inhabited by tamoxifen and chloroquine in retinal epithelial cells and Also, a study demonstrated that Tamoxifen have weak base property and increase endolysosomal pH and alter endosomal dynamics. Importantly, TAM treatment enhanced survival of mice injected with a lethal dose of STx1 or STx2,The protective effect was independent of estrogen receptors but dependent on the weak base property of TAM, which allowed TAM to increase endolysosomal pH and alter endosomal dynamics. A study demonstrated that Tamoxifen have antimalarial effect via treating mice infected with P. berghei, which show lower levels of parasitaemia and do not develop signs of cerebral malaria, Tamoxifen is found to prevent lung fibrosis and reduce serum TGFβ-1 levels. A study Reported that Tamoxifen have endosomal and lysosomal cysteine proteases inhibitory effect better than chloroquine , Cathepsins are endosomal and lysosomal cysteine proteases that play important roles in protein degradation in various cellular processes including both the endocytic pathway and autophagy. The role of cathepsins in viral infection was first identified by Huang et al and they found that one cysteine proteases inhibitor E64d and a specific cathepsin L inhibitor Z-FY(t-Bu)-DMK are able to block the SARS-CoV infection. A study demonestrated that Cathepsin D was more sensitive to tamoxifen than to chloroquine. Tamoxifen exposures decreased the cathepsin D activity at less than 10 pM concentrations. The effect of chloroquine started at concentration of 15 pM,The third drug Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections it contains in its structure sulfonamides . More than one study demonstrated that sulfonamides elevate endosomal and lysosomal pH, down-regulate cell surface receptors, and impair recycling of internalized transferrin receptors to the plasma membrane. Finally, the principal investigator expects strong inhibition of COVID-19 by this triple therapy. Keywords: COVID 2019 , Isotretinoin , Tamoxofin, ACE2,.Endosomal and Lysosomal pH.
Description: Proportion of lung injury score decreased or increased after treatment
Measure: lung injury score Time: at 7 daysDescription: lymphocyte counts
Measure: Absolute lymphocyte counts Time: at day 7 and 14Description: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon
Measure: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon Time: at day 7 and 14Description: Serum level of COVID19 RNA
Measure: Serum level of COVID19 RNA Time: at day 7 and 14Description: less than 250 ng/mL, or less than 0.4 mcg/mL of blood sample
Measure: d-dimers Time: at 3-5 daysDescription: (if pos. at baseline)
Measure: Time to first negative SARS-CoV-2 PCR in NP swap Time: 14 daysSAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra.
Description: Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment
Measure: Proportion of patients with a positive SARS-CoV-2 PCR Time: 7 days post-treatmentDescription: Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab
Measure: Mean viral load Time: Baseline and on days 4, 7, 14 and 21Description: Proportion of patients with fever and cough at days 4, 7, 14 and 21 as well as proportion of patients progressing to severe disease or death during the trial
Measure: Fever and cough progression Time: Up to and including day 21Description: Proportion of participants with positive IgG at day 21
Measure: Seroconversion at day 21 Time: Up to and including day 21Description: Proportion of drug-related adverse events
Measure: Proportion of drug-related adverse events Time: 7 days post treatmentDescription: Levels in median fluorescence intensity (MFI) of IgG, IgM and IgA against the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 in plasma, measured by a Luminex assay
Measure: Levels of IgG, IgM and IgA Time: Up to and including day 28Description: Frequency (% over total PBMC) of innate immune cells (myeloid and plasmacytoid dendritic cells, NK cell, classical, intermediate and pro-inflammatory macrophages) measured in cryopreserved PBMC by flow cytometry
Measure: Frequency of innate immune cells Time: Up to and including day 7Description: Frequency of CD4+ T and CD8+ T cells (% over total CD4+T and CD8+ T) expressing any functional marker upon in vitro stimulation of PBMC with SARS-CoV-2 peptides, measured by flow cytometry
Measure: Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T cells Time: Up to and including day 7Description: Concentration (all in pg/mL) of epidermal growth factor (EGF), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1RA, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p40/p70), IL-13, IL-15, IL-17, IFN-γ induced protein (IP-10), monocyte chemoattractant protein (MCP-1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1β in plasma measured by a Luminex assay using a commercially available kit (Cytokine Human Magnetic 30-Plex Panel from ThermoFisher)
Measure: Results from cytokine Human Magnetic 30-Plex Panel Time: Up to and including day 28The Malaysian COVID-19 Anosmia Study is a nationwide multicentre observational study to investigate the prevalence and characteristics of olfactory and gustatory/taste disturbances in COVID-19 infection in Malaysia, and to evaluate the predictive value of screening for these symptoms in COVID-19 infection. This study consists of two phases: the first phase is a cross-sectional study and the second phase is a case-control study. The cross-sectional study is described here (the case-control study is described in a separate ClinicalTrials.gov record).
Description: In the patient-reported online questionnaire, subjects will be asked regarding whether they experienced symptoms of olfactory and/or taste disturbances
Measure: Presence or absence of olfactory and taste disturbances in COVID-19 patients Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: Percentage of COVID-19 patients experiencing olfactory disturbances (anosmia or hyposmia)
Measure: Prevalence of olfactory disturbances in COVID-19 patients Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: Percentage of COVID-19 patients experiencing taste disturbances
Measure: Prevalence of taste disturbances in COVID-19 patients Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked regarding other symptoms they experienced when they were diagnosed with COVID-19 (e.g. headache, nasal congestion, fever, chills, cough, dyspnoea, gastrointestinal symptoms, eye & ear symptoms)
Measure: Clinical manifestations of study participants Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked regarding their pre-existing health conditions (for example, obesity, diabetes, hypertension, cardiac conditions, previous head trauma, chronic rhinosinusitis, etc.)
Measure: Other pre-existing health conditions Time: Prior to diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked to rate their sense of smell and taste before their diagnosis of COVID-19 infection
Measure: Rating of baseline sense of smell & taste in COVID-19 patients prior to diagnosis of their infection Time: Prior to 2 weeks preceding the diagnosis of COVID-19 infection (Baseline)Description: In the patient-reported online questionnaire, subjects will be asked to rate their sense of smell and taste at the time of diagnosis of COVID-19 infection
Measure: Rating of sense of smell & taste in COVID-19 patients at time of diagnosis of their infection Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked to rate their sense of smell and taste at the time of answering questionnaire survey
Measure: Rating of sense of smell & taste in COVID-19 patients at time of answering questionnaire survey Time: Up to 6 monthsModerate to severe cases of SARS-associated ARDS based on inclusion/ exclusion criteria and the decision made in multi- disciplinary team are treated with 0.5 Gy whole lung radiation.
Description: PaO2 / FiO2
Measure: Change from baseline blood oxygenation Time: 28 daysDescription: Total days the patient is admitted to hospital
Measure: Number of Hospital stay days Time: 28 daysDescription: Total days the patient is admitted to ICU
Measure: Number of ICU stay days Time: 28 daysDescription: Total number of intubations performed after the treatment
Measure: Number of intubation events Time: 28 daysDescription: Changes in WBC count
Measure: WBC Time: 28 daysDescription: Changes in Platelets count
Measure: Platelets Time: 28 daysDescription: Changes in ESR measurement
Measure: ESR Time: 28 daysDescription: Changes in CRP serum level
Measure: CRP Time: 28 daysDescription: Changes in IL-6 serum level
Measure: IL-6 Time: Day 1Description: Changes in IL-6 serum level
Measure: IL-6 Time: Day 4Description: Changes in IL-6 serum level
Measure: IL-6 Time: Day 7Description: Changes in IL-6 serum level
Measure: IL-6 Time: Day 14Description: any radiological change in CT scan
Measure: Chest CT scan Time: Day 1Description: any radiological change in CT scan
Measure: Chest CT scan Time: Day 7Description: any radiological change in CT scan
Measure: Chest CT scan Time: Day 14Description: any radiological change in CT scan
Measure: Chest CT scan Time: Day 28A prospective case-control pilot study to evaluate the possible effect of a probiotic mixture in the improvement of symptoms, the reduction in the number of days of hospitalization and the increase in the percentage of patients with negative PCR after infection with the coronavirus SARS-CoV-2.
Description: Percentage of patients with discharge to ICU.
Measure: Cases with discharge to ICU. Time: 30-daysDescription: Percentage of patients with home discharge.
Measure: Patients with home discharge. Time: 30-daysDescription: Percentage of deaths.
Measure: Mortality. Time: 30-daysDescription: Number of adverse events that occur during the treatment period, attributable or not to the intervention product.
Measure: Treatment safety assessed by number of adverse events. Time: 30-daysDescription: Number of new cases of positive SARS-Cov-2 infection by PCR analysis.
Measure: New cases of SARS-Cov-2 infection among healthcare personnel caring for the patients. Time: 30-daysDescription: Percentage of patients with negative PCR for SARS-CoV-2.
Measure: Patients with negative PCR result for SARS-CoV-2 infection. Time: 30-daysProne position (PP) has been proved to be effective in severe ARDS patients. On the other hand, High flow nasal cannula (HFNC) may prevent intubation in hypoxemic Acute respiratory failure (ARF) patients. Our hypothesis is that the combination of PP and HFNC in patients with COVID19 induced ARDS may decrease the need of mechanical ventilation. Primary outcome: Therapeutic failure within 28 days of randomization (death or intubation). Secondary outcomes: to analyze PP feasibility and safety in HFNC patients and to analyze effectiveness in terms of oxygenation. Methods: multicentric randomized study including patients with COVID19 induced ARDS supported with HFNC. Experimental group will received HFNC and PP whereas observation group will received standard care. Optimization of non-invasive respiratory management of COVID19 induced ARDS patients may decrease the need of invasive mechanical ventilation and subsequently ICU and hospital length of stay.
Description: Therapeutic failure: death or intubation
Measure: Therapeutic failure death or intubation Time: 28 days within randomizationDescription: Comfort measurement using a visual-analog scale. Presence of complications related with prone position and the use of high-flow nasal cannula: Skin ulcers. Intravascular lines displacement HFNC related events (hot air feeling, nasal lesions)
Measure: Feasibility and safety of prone position in HFNC patients Time: 28 days within randomizationDescription: Evolution of the oxygenation (SpO2/FiO2) in prone position. Efficacy Length of HFNC therapy Length of ICU stay Length of mechanical ventilation (in those who require intubation) ICU and hospital mortality
Measure: Efficacy of prone position in HFNC patients Time: 28 days within randomizationThe most severe manifestations of COVID-19 include respiratory failure, coagulation problems, and death. Inflammation and blood clotting are believed to play an important role in these manifestations. Research in humans has shown that dipyridamole can reduce blood clotting. This research study is being conducted to learn whether 14 days of treatment with dipyridamole will reduce excessive blood clotting in COVID-19. This study will enroll participants with confirmed coronavirus (SARS-CoV)-2 infection that are admitted to University of Michigan. Eligible participants will be randomized to receive dipyridamole or placebo for 14 days in the hospital. In addition, data will be collected from the medical record, and there will also be blood draws during the hospitalization.
Description: Increase in plasma D-dimer level compared with baseline at enrollment.
Measure: Change in D-dimer Time: baseline, up to approximately 28 days after last study drug administrationDescription: Global composite rank score of death, mechanical ventilation, oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2), and World Health Organization (WHO) Ordinal score.
Measure: Global composite rank score Time: up to approximately 28 days after last study drug administrationThe objectives of the study, are to describe detection of SARS-CoV-2 in the semen of COVID-19 positive patients, the duration of positive semen and to investigate the impact on semen quality, thereby providing insights into the early impact on male reproductive function.
Description: detection of SARS-CoV-2 in the semen of men positive for SARS-CoV-2 on nasopharyngeal swab
Measure: detection of SARS-CoV-2 in the semen Time: within 7 days after positive testing for SARS-CoV-2Description: in case of a positive SARS-CoV-2 semen sample, for how long stays the virus present in semen
Measure: duration of SARS-CoV-2 presence in semen Time: from first positive semen testing until first negative semen testing, upto 15 weeksDescription: viscosity of semen will be assessed macroscopically
Measure: semen viscosity Time: from first until last semen analysis, upto 15 weeksDescription: semen volume
Measure: semen volume Time: from first until last semen analysis, upto 15 weeksDescription: semen pH
Measure: semen pH Time: from first until last semen analysis, upto 15 weeksDescription: Sperm motility assesment, according to the WHO guidelines of 2010
Measure: Sperm motility Time: from first until last semen analysis, upto 15 weeksDescription: Sperm morphology assesment, according to the WHO guidelines of 2010
Measure: Sperm morphology Time: from first until last semen analysis, upto 15 weeksDescription: Sperm density assesment, according to the WHO guidelines of 2010
Measure: Sperm density Time: from first until last semen analysis, upto 15 weeksThis study aims to use the regenerative and repair abilities of stem cells to fight against the harmful effects of the novel coronavirus Covid-19 and therefore develop a treatment strategy. It is known that fatalities from this virus is largely caused by its damage to lungs and other organs. As the disease progresses, these organs fail and lead to mortality. Our hope is that the stem cell transplantation from healthy donors will repair the damage caused by the virus and result in a healthy recovery.
Description: Improvement of clinical symptoms related to Covid-19 infection (fever, pneumonia, shortness of breath)
Measure: Clinical improvement Time: 3 monthsDescription: Improvement of lungs assessed by CT Scan
Measure: Lung damage improvement Time: 3 monthsDescription: Negative, measured by RT-PCR laboratory tests for the virus
Measure: Sars-Cov-2 viral infection laboratory test Time: 3 monthsDescription: Cell types and numbers
Measure: Blood test Time: 3 monthsSARS-CoV-2 has now crossed the 1 million number of cases and tens of thousands of deaths. It´s R0 has been calculated between 2 and 5.7 solely based on clinical symptoms but it is estimated to lickely be higher. Seroloic evidence of infection has not been analyzed.
Description: Identify the presence of IgM and IgG antibodies from intradomestic contacts of patients with PCR for detected SARS-CoV-2 .
Measure: Identify antibodies Time: 1 dayDescription: Determine the sensitivity of IgM and IgG antibody detection by ELISA in direct eastern contacts of patients with PCR for detected SARS-CoV-2.
Measure: Determine antibody sensitivity Time: 1 dayDescription: Determine the presence of IgM antibodies by ELISA in direct eastern contacts of patients with detected SARS-CoV-2 PCR.
Measure: IgM determination Time: 1 dayDescription: Determine the presence of IgG antibodies by ELISA in direct eastern contacts of patients with detected SARS-CoV-2 PCR.
Measure: IgG determination Time: 1 dayCOVID-19 is highly infectious and transmission of the virus is thought to be similar to that of influenza which can be transferred through droplets released when a person coughs, sneezes or talks. Studies have shown that nasal rinsing and mouth washes may be an important way to deliver treatments that could reduce the amount of a virus that is present in the nose and mouth. This also could mean that there is less virus available to pass on to others. We want to see if the use of nose rinses and mouth washes using Povidone-Iodine will reduce the the amount of virus in the nose and throat of people who have tested positive for COVID-19 disease and also reduce the spread of infection within their household.
Description: viral load as measured by real time polymerase chain reaction (PCR)
Measure: Change in viral load in the oral and nasopharyngeal cavity Time: Day 0, 2, 3, 7, 14Description: Visual analogue score 1-5 per symptom via a smartphone app
Measure: Symptom severity in primary participants and co-residents Time: Days 0 to 14Short description of the protocol intended for the lay public. Include a brief statement of the study hypothesis (Limit : 5000 characters) The management of critically-ill patients with organ failure due to COVID-19 represents a major healthcare burden. While endothelial inflammation has been reported in these patients, the pathophysiological mechanisms remain incompletely elucidated.
Pragmatic randomized clinical trial of patients admitted to the hospital with confirmed COVID-19 infection and elevated D-Dimer. Randomization 1:1 - Group 1 will undergo a routine full anticoagulation (oral or parenteral when needed) strategy; and group 2 will receive usual standard of care with prophylactic anticoagulation
Description: The primary objective will be analyzed using the win ratio approach comparing every participant of treatment group to every participant of control group to determine a winner.
Measure: Hierarchical composite endpoint composed of mortality, number of days alive, number of days in the hospital and number of days with oxygen therapy at the end of 30 days. Time: In 30 daysDescription: It will be considered the main safety endpoint
Measure: Incidence of Major bleeding and clinically relevant non-major bleeding by the ISTH criteria Time: In 30 daysProne positioning is an established intervention in mechanically ventilated acute respiratory distress syndrome (ARDS) patients, with demonstrated reductions in mortality. Preliminary data suggest that awake proning in patients with COVID-19 treated with high-flow nasal oxygenation (HFNO) improves gas exchanges, and might be associated with a reduced need of mechanical ventilation, and reduced mortality. Further investigation in a formal randomized-controlled trial is need.
Description: Total time spent in prone position, as recorded by nursing or respiratory therapists
Measure: Time in prone position Time: Up to 28 days post randomizationDescription: Daily evolution of oxygenation
Measure: Oxygenation (SpO2/FiO2 ratio) Time: Until HFNC weaning, or up to 14 days after randomization, whichever is firstThis is a Phase I open-label interventional study which will test the efficacy of ResCure™ in the treatment of patients with COVID-19 infection.
Description: Number of days from COVID-19 diagnosis to recovery via RT-PCR
Measure: The rate of recovery of mild or moderate COVID-19 in patients using ResCure™ Time: 12 WeeksDescription: Reduction and/or progression of symptomatic days, reduction of symptom severity
Measure: Reduction or progression of symptomatic days Time: 12 WeeksDescription: Pulse from baseline to 12 weeks
Measure: Assess the safety of ResCure™ via pulse Time: 12 WeeksDescription: Oxygen saturation from baseline to 12 weeks
Measure: Assess the safety of ResCure™ via oxygen saturation Time: 12 WeeksDescription: EKG from baseline to 12 weeks
Measure: Assess the safety of ResCure™ via EKG Time: 12 WeeksDescription: Assess Adverse Events and Serious Adverse Events due to ResCure™
Measure: Assess Tolerability of ResCure™ Time: 12 WeeksThe present study aims to assess the impact of exercise training, physical activity, and sedentary lifestyle on clinical outcomes in surviving patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, this study will evaluate cross-sectionally and through a questionnaire in Portuguese and English on the internet, whether physically active patients have better outcomes for the disease such as shorter hospital stay, lesser symptoms, lesser need for mechanical ventilation, and medications.
Description: Number of hospitalizations required due to COVID-19
Measure: Number of hospitalizations Time: Up to 6 months after hospital discharge and/or full recovery from the disease (asymptomatic)Description: Symptoms such as fever, cough, shortness of breathe, and muscle pain due to COVID-19
Measure: Percentage of symptoms of the disease Time: Up to 6 months after hospital discharge and/or full recovery from the disease (asymptomatic)Description: Length of hospital stay required due to COVID-19
Measure: Length of hospital stay Time: Up to 6 months after hospital discharge and/or full recovery from the disease (asymptomatic)Description: Need for mechanical ventilation during hospitalization due to COVID-19
Measure: Percentage of mechanical ventilation Time: Up to 6 months after hospital discharge and/or full recovery from the disease (asymptomatic)COVID-19 patients with a severely symptomatic progression with development of an Acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 need prolonged intensive care treatment involving pharmacological immobilization, sedation and mechanical ventilation, leaving them at a very high risk for developing Critical illness myopathy (CIM). CIM is associated with increased mortality and significant consequences for recovery and the ability to return to normal daily life. Up to date, there are no studies investigating the mid- or long-term course of the novel COVID-19 disease. The present study therefore aims to evaluate the clinical outcome of patients with ARDS due to SARS-CoV-2 with special attention to the development of CIM and its underlying causes. To provide the possibility of early diagnosis of CIM, critically ill patients will be regularly screened for muscle membrane alterations using (Muscle velocity recovery cycles) MRVC measurements. The primary endpoint is the incidence of CIM in patients with ARDS due to SARS-CoV-2, diagnosed according to the current diagnostic criteria.
Description: Short Form (36) Health Survey (SF-36)
Measure: Short Form (36) Health Survey (SF-36) Time: 3 monthsDescription: Mortality
Measure: Mortality Time: 90 daysDescription: Modified Rankin Scale (mRS); (0=no Symptoms at all, 6=dead)
Measure: Modified Rankin Scale (mRS) Time: 90 daysDescription: Duration of mechanical ventilation in days
Measure: Duration of mechanical ventilation in days Time: 3 monthsDescription: Barthel Index (80-100= patient should be able to live independently, <20=total dependence)
Measure: Barthel Index Time: 3 monthsDescription: Beck's Depression Inventory II (BDI-II)
Measure: Beck's Depression Inventory II (BDI-II) Time: 3 monthsDescription: Essener Questionnaire for Coping with a Disease (EFK); (0=no burden of disease, 180-strong burden of disease)
Measure: Essener Questionnaire for Coping with a Disease (EFK) Time: 3 monthsDescription: Number of patients with Critical Illness Myopathy
Measure: Number of patients with Critical Illness Myopathy Time: day 10The role of ECMO in the treatment of patients with severe COVID-19 (Acute Respiratory Distress Syndrome (ARDS) and/or acute refractory heart failure) is not yet known. The present study will aim to report the results of the ECMO management of the most severe forms of COVID-19 through the first French ECMO registry.
Description: Hospital mortality
Measure: Hospital mortality Time: up to 90 daysDescription: Mortality Day 28
Measure: Mortality Day 28 Time: Day 28Description: Mortality Day 90
Measure: Mortality Day 90 Time: Day 90Description: Ventilator-free days
Measure: Ventilator-free days Time: Day 28Description: ICU-free days
Measure: Intensive care unit-free days Time: Day 28Description: Hospital-free days
Measure: Hospital-free days Time: Day 28The purpose of this open label, randomized, study is to obtain information on the safety and efficacy of 80 ppm Nitric Oxide given in addition to the standard of care of patients with COVID-19 caused by SARS-CoV-2.
Description: Time to deterioration measured by need for NIV, HFNC or intubation need for high flow nasal cannula (HFNC) or need for intubation
Measure: Time to deterioration Time: 14 DaysDescription: Time to non-invasive ventilation
Measure: Time to non-invasive ventilation Time: 14 DaysDescription: Time to HFNC
Measure: Time to HFNC Time: 14 DaysDescription: Time to intubation
Measure: Time to intubation Time: 14 daysDescription: Time to patient having stable oxygen saturation (SpO2) greater than 92%
Measure: Time to patient having stable oxygen saturation (SpO2) greater than 92% Time: 14 daysDescription: Need for supplemental oxygen
Measure: Need for supplemental oxygen Time: 14 daysDescription: Change in viral load
Measure: Change in viral load Time: 30 daysDescription: Duration of the Hospital Length of Stay (LOS)
Measure: Duration of the Hospital Length of Stay (LOS) Time: 14 daysRecent information appearing from different countries suggest that treatment of Coronavirus disease 2019 (COVID-19) with hydroxychloroquine or with a combination of hydroxychloroquine and azithromycin has either an indifferent effect on viral replication or substantial cardiotoxicity. This is a clinical trial aiming to prove that addition of oral clarithromycin to treatment regimen of COVID-19 is associated with early clinical improvement and attenuation of the high inflammatory burden of the host. The study will not comprise a placebo-comparator group since this is considered inappropriate in an era of a pandemic with substantial global mortality.
Description: This is defined on day 8 (End of Treatment - EOT). Patients with upper respiratory tract infection by SARS-CoV-2 meet the study primary endpoint if they were not admitted to hospital or their symptoms did not progress to lower respiratory tract infection. Patients who develop by day 8 severe respiratory failure do not meet the study primary endpoint.
Measure: Clinical outcome negative for two parameters(hospital admission/disease progression) Time: Day 1 to Day 8Description: This is defined on day 8 (EOT visit). Patients with lower respiratory tract infection by SARS-CoV-2 meet the primary endpoint if they present at least 50% decrease of the score of respiratory symptoms from the baseline. This score is the sum of scoring for the symptoms of cough, dyspnea, purulent sputum expectoration and pleuritic chest pain. Patients who develop by day 8 severe respiratory failure do not meet the study primary endpoint. Score ranges from 0 (no symptoms) to 9 (worst for all symptoms).
Measure: At least 50% decrease of the score of respiratory symptoms from the baseline Time: Day 1 to Day 8Description: Evaluation of need of hospitalization, SARS-CoV-2 infection progression from upper to lower respiratory tract infection, between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of two parameters with historical comparators from Hellenic Sepsis Study Group Database Time: Day 1 to Day 8Description: Respiratory score evaluation as described above between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of the score of respiratory symptoms with historical comparators from Hellenic Sepsis Study Group Database Time: Day 1 to Day 8Description: Comparison of clinical data (need of hospitalization, the infection progression of SARS-CoV-2 from upper to lower respiratory tract infections) in enrolled patients between baseline and study visit day 4 Patients who develop by day 4 severe respiratory failure do not meet the study secondary endpoint.
Measure: Clinical outcome negative for two parameters(hospital admission/disease progression) on day 4 Time: Day 4Description: This is defined on day 4 (5th visit). Patients with lower respiratory tract infection by SARS-CoV-2 meet the secondary endpoint if they present at least 50% decrease of the score of respiratory symptoms from the baseline. This score is the sum of scoring for the symptoms of cough, dyspnea, purulent sputum expectoration and pleuritic chest pain. Patients who develop by day 4 severe respiratory failure do not meet the study secondary endpoint. Score ranges from 0 (no symptoms) to 9 (worst for all symptoms).
Measure: At least 50% decrease of the score of respiratory symptoms from the baseline on day 4 Time: Day 4Description: Evaluation of range of enrolled patients who develop severe respiratory failure between baseline and day 14 (TOC VISIT). Severe respiratory failure is defined by presence of all of the following pO2/FiO2 less than 150 Need for mechanical or non-mechanical ventilation (CPAP)
Measure: Range of development of severe respiratory failure Time: Day 1 to Day 14Description: Evalution of hospital readmission until day 14 (TOC VISIT) from enrollement defined as either need of re-hospitalization for discharged patients or any need for hospitalization of out-patients.
Measure: Range of hospital readmission until day 14 Time: Day 1 to Day 14Description: Comparison of Real Time - Polymerase Chain Reaction (RT-PCR) results for SARS-CoV-2 viral load in rhinopharyngeal samples of enrolled patients at days 1, 4 and 8
Measure: Change of viral load in respiratory secretions from baseline on day 8 Time: Day 1 to Day 8Description: Change of cytokine production of monocytes in enrolled patients with upper/lower respiratory tract infection at days 1 and 8 (EOT) visit; monocytes will be stimulated for 24 hours with SARS-CoV-2 purified antigens for the production of TNFα. This will be analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of function of monocytes at days 1 and 8 Time: Day 1 to Day 8Description: Change of cytokine production of Th1 cells in enrolled patients with upper/lower respiratory tract infection at days 1 and 8 (EOT) visit; Th1 cells will be stimulated for 24 hours with SARS-CoV-2 purified antigens for the production of IFNγ. This will be analyzed separately for patients with upper and with lower respiratory tract infection.
Measure: Change of function of Th1 cells at days 1 and 8 Time: Day 1 to Day 8Description: Change of cytokine production of Th2 cells in enrolled patients with lower respiratory tract infection at days 1 and 8 (EOT) visit; Th2 cells will be stimulated for 24 hours with SARS-CoV-2 purified antigens for the production of IL6. This will be analyzed separately for patients with upper and with lower respiratory tract infection.
Measure: Change of function of Th2 cells at days 1 and 8 Time: Day 1 to Day 8Description: Change of the serum levels of interleukin-6 (IL-6) of enrolled patients between day 1 and day 8 (EOT VISIT); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of serum interleukin-6 (IL-6) cytokine levels between days 1 and 8 Time: Day 1 to day 8Description: Change of the serum levels of interleukin-8 (IL-8) of enrolled patients between day 1 and day 8 (EOT VISIT); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of serum interleukin-8 (IL-8) cytokine levels between days 1 and 8 Time: Day 1 to day 8Description: Change of the serum levels of human beta defensin-2 (hBD-2) of enrolled patients between day 1 and day 8 (EOT VISIT); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of serum human beta defensin-2 (hBD-2) between days 1 and 8 Time: Day 1 to day 8Description: Change of rhinopharynx levels of interleukin-6 (IL-6) of enrolled patients between day 1, day 4 and day8 (EOT visit); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of cytokine levels interleukin-6 (IL-6) at the rhinopharynx between days 1,4 and 8 Time: Day 1 to day 8Description: Change of rhinopharynx levels of interleukin-1 (IL-1) of enrolled patients between day 1, day 4 and day8 (EOT visit); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of interleukin-1 (IL-1) cytokine levels at the rhinopharynx between days 1,4 and 8 Time: Day 1 to day 8Description: Comparison of the Interleukin-10/Tumor Necrosis Factor α (IL-10/TNFα) ratio in enrolled patients at days 1 and 8; this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of the IL-10/TNFα ratio between days 1 and 8 Time: Day 1 to Day 8In December 2019, Coronavirus infection (COVID-19) was identified as causing serious respiratory infection in humans. Initially COVID-19 was propagated by infected symptomatic individuals; currently the disease is disseminated by asymptomatic COVID-19 positive subjects. The prevalence of asymptomatic COVID-19 individuals is unknown. Due its physiologic immune suppression, pregnancy is a vulnerable time for severe respiratory infections including COVID-19. Limited information is available regarding the impact of COVID-19 in pregnancy and the prevalence and demographic profile of asymptomatic pregnant women. Despite reports of 15-20% positive COVID-19 tests in women admitted to Labor and Delivery, professional obstetric medical societies still recommend not prioritizing testing of patients who are asymptomatic. In the USA, COVID-19 symptomatic patients come predominantly from lower income, Black and Latino communities. No data are available on the rate and demographic distribution of asymptomatic positive COVID-19 pregnant women. To minimize the risk of inadvertent exposure asymptomatic individuals, recently our institution started COVID-19 testing in all admitted pregnant women. The investigators expect to gain knowledge on the impact of COVID-19 in pregnant women especially if asymptomatic and compare to other respiratory infections.
Description: Rate of asymptomatic pregnant women who test positive for COVID-19 at the time of hospital admission
Measure: Asymptomatic COVID-19 positive pregnant women Time: Through completion of the study, an average of 1 yearDescription: Rate of Hispanic pregnant women among those asymptomatic COVID-19 positive on admission
Measure: Asymptomatic Hispanic COVID-19 positive pregnant women Time: Through completion of the study, an average of 1 yearDescription: Rate of asymptomatic positive pregnant women who later will develop COVID-19 related symptoms
Measure: Follow up of asymptomatic COVID-19 positive pregnant women Time: Through completion of the study, an average of 1 yearDescription: Prevalence of COVID-19 positive newborns from infected mothers
Measure: COVID-19 positive newborns Time: Through completion of the study, an average of 1 yearDescription: Rate of COVID-19 positive pregnant women who develop respiratory / multi-organ complications requiring admission to Medicine or Intensive Care units / maternal death related to COVID-19
Measure: Severe COVID-19 disease in pregnant women Time: Through completion of the study, an average of 1 yearThe objective of the study is to assess the efficacy and safety of Baricitinib in the treatment of patients with COVID-19 pneumonia. This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof of concept phase will lead to favourable results, an open-label, Phase II, randomized controlled trial will be then designed and performed to confirm the results obtained in the proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on a limited number of patients in the use of a drug new to the current condition being treated.
Description: A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)
Measure: Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria) Time: 8 daysDescription: Absence of death within 8 days from enrollment
Measure: Response to treatment: survival Time: 8 daysDescription: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days Time: 8 daysDescription: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)
Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days Time: 15 daysDescription: To quantify mortality within 8 and 15 days
Measure: Mortality Time: 8 days and 15 daysDescription: SpO2 will be assessed with the median and 25th-75th percentiles
Measure: Peripheral capillary oxygen saturation (SpO2) Time: 8 days; 15 daysDescription: PaO2/FiO2 will be assessed with the median and 25th-75th percentiles
Measure: Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2) Time: 8 days; 15 daysDescription: Number of patients over the number of patients enrolled
Measure: To assess the rate of patients admitted to the intensive care unit Time: 8 days; 15 daysDescription: Median number of days and 25th-75th percentiles
Measure: To measure the length of hospital stay Time: 8 days; 15 daysDescription: To quantify 28-day mortality
Measure: 28-day mortality Time: 28 daysDescription: Number of patients readmitted over the number patients enrolled
Measure: To quantify the rate of re-admission within 28 days Time: 28 daysDescription: Number, type, and severity of adverse events
Measure: To quantify the cumulative incidence and severity of adverse events Time: 28 daysDescription: Serial serum assessments from baseline up to 15 days
Measure: Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels; Time: 15 daysDescription: Serial serum assessments from baseline up to 15 days
Measure: TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels Time: 15 daysDescription: Serial assessments from baseline up to 15 days for viral load persistence
Measure: Viral load analyses Time: 15 daysThis is a 30 patient, Phase 1/2a multi-center pilot study to test the safety and to describe the preliminary efficacy of intravenous administration of allogenic human cord tissue mesenchymal stromal cells (hCT-MSC) as an investigational agent, under U.S. IND 19968 to patients with acute respiratory distress syndrome (ARDS) due to COVID-19 infection (COVID-ARDS). The key secondary endpoints are 28 day survival, an increase in PaO2/FiO2 ratio by 50% at 96 hours, days to hospital discharge to home or rehab, and number of days requiring mechanical ventilation. Patients will be eligible for treatment with 3 daily consecutive doses of hCT-MSC at 1 million cells/kg (max dose 100 million cells), 18-30 hours apart, if they have a confirmed diagnosis of COVID-19 and meet clinical and radiographic criteria for ARDS. Results from the first 10 patients will be compared with concurrent outcomes utilizing standard of care treatments in participating hospitals and in published reports in the medical literature. Results from the additional 20 patients will be combined with the first 10 and analyzed. The trial is relying on focused eligibility of the participants (patients with ARDS), single cohort with short trial time (4 weeks), and simple assessment of clinical outcome (survival, improvement of ARDS). This is a sequential design in the sense that after the first 10 patients are evaluated a decision will be made by the PIs and the Data Safety Monitoring Board whether to proceed with the exploratory randomized portion of the study.
Description: Incidence of infusion reactions measured by any one of the following: fever, anaphlyaxis, rash, hypertension, hypotension, tachycardia, nausea, vomiting, or any other new or worsening symptoms associated with the infusion.
Measure: Safety of the Investigational Product Time: 24 hoursDescription: Incidence of later reactions attributed to the investigational product as measured by any one of the following: rash, infection, allergic reaction, or any other symptoms associated with infusion of the investigational product.
Measure: Safety of the Investigational Product Time: 28 daysDescription: Formation of new anti-PRA antibodies as measured by an antibody screen test at 28 days post first infusion of the investigational product.
Measure: Safety of the Investigational Product Time: 28 daysDescription: Survival after 28 days after the first dose of MSCs
Measure: Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs Time: 28 daysDescription: Increase in PaO2/FiO2 ratio by 50%
Measure: Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs Time: 3 days after MSCsDescription: The number of days from hospitalization to discharge to home
Measure: Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs Time: 90 daysDescription: The number of ventilator free days
Measure: Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs Time: 90 daysDescription: A 50% decrease in opacities by CT chest one week post initiation of MSC therapy
Measure: Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs Time: 7 daysDescription: The number of days requiring oxygen support
Measure: Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs Time: 90 daysDescription: Changes in viral load after MSCs measured by routine PCR testing from baseline to 4 days, 7 days and 28 days after MSCs
Measure: Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs Time: baseline, day 4, day 7, and day 28Description: Number of patients able to be on the randomized portion of this study
Measure: Describe the potential for MSC therapy to favorably alter the course of COVID-ARDs Time: 90 daysCoronavirus has already infected 4,673,809 people and killed 312,646 people worldwide, and no specific treatment or a vaccine against it has yet proven to be effective. Ozone therapy has become o promising tool for both prevention and treatment of COVID-19 infection by various possible mechanisms. The oxidative stress created by ozone in the body to stimulate the peripheral phagocytic cells, activate the antioxidant system, and restore the immune system is thought to be effective for the prevention of COVID-19 infection. In recent years, ozone therapy has become a popular alternative method for chronic pain management of various diseases such as fibromyalgia, knee osteoarthritis, and rheumatic diseases. As a result of this, there were many individuals who had received ozone therapy before the outbreak of COVID-19. This study aimed to investigate the preventive effect of ozone therapy against COVID-19 infection in these individuals.
Description: It involved questions about age, gender, height, weight, occupation, comorbidities, and concurrent medications, in addition to a detailed query for COVID-19 infection
Measure: The survey that was taken by telephone calls Time: Day 0Professionals and residents of nursing homes are one of the most vulnerable groups in this public health crisis of COVID-19, since they have the highest rate of positives for COVID-19, despite the restriction measures carried out, such as prohibition of family visits to these centers, the infection occurs by cross transmission with the care staff of the centers, or with other residents. At the moment, there are no clinical trials to test the hypothesis that hydroxychloroquine is effective in coronavirus treatment. Although what has been observed is a better prognosis in infected patients, since this drug inhibits the replication of the virus and its expansion to other tissues. This study is a clinical trial to test the effectiveness of hydroxychloroquine as a preventive drug for SARS-CoV-2 infection. This drug will be applied to 1050 people residing in nursing home care and 880 professionals who work in close contact with these people and who have not yet contracted the infection. This project will be carried out in the territories of Madrid, Navarra, Aragon and Andalusia (Spain). Hydroxychloroquine is a widely known drug that is used in two scenarios, against autoimmune diseases, such as lupus or rheumatoid arthritis, and as an antimalarial drug. It is also intended to demonstrate that the presumed reduction in viral load that would be obtained with hydroxychloroquine prophylaxis, would have no effect in development of immunity against the virus. This fact can create a new paradigm for the de-escalation of the confinement to which the population has been subjected to stop the virus spread, allowing the development of general immunity in controlled populations until reaching total immunity. In addition to testing the effect of this drug, a non-pharmacological intervention based on a safety record will be tested in the management of infection on nursing home, to assess its effectiveness in detecting risk areas or bad practices carried out in this vulnerable environment. The study is led by researchers of the Institute of Biomedicine of Malaga (Spain), and has obtained a financing of 1,024,199 euros from Carlos III Health Institute (Spain). The period of execution of the clinical trial is one year, and with this intervention, the intention is to reduce cross-infection in residents by a minimum threshold of 15%, as well as to decrease infection in the professionals.
Description: Discrete quantitative variable. Residents with active viral load (diagnosed by polymerase chain reaction test) will be considered infected.
Measure: Number of secondary cases of SARS-CoV2 infection among residents at six days Time: This outcome will be evaluated at six days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Discrete quantitative variable. Residents with active viral load (diagnosed by polymerase chain reaction test) will be considered infected.
Measure: Number of secondary cases of SARS-CoV2 infection among residents at 14 days Time: This outcome will be evaluated at 14 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Discrete quantitative variable. Residents with active viral load (diagnosed by polymerase chain reaction test) will be considered infected.
Measure: Number of secondary cases of SARS-CoV2 infection among residents at 28 days Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable
Measure: SARS-CoV-2 infection in nursing home staff who provide direct care at six days Time: This outcome will be evaluated at six days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable
Measure: SARS-CoV-2 infection in nursing home staff who provide direct care at 14 days Time: This outcome will be evaluated at 14 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable
Measure: SARS-CoV-2 infection in nursing home staff who provide direct care at 28 days Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous qualitative variable (1: Death 0: Survival)
Measure: Mortality Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Continous variable. It will be evaluated with the AIDS Clinical Trials Group method: investigation of medications not taken in a period of 4 days prior to the interview)% adherence = (total prescribed galenic units for that period-total units not taken) / total prescribed galenic units for that period
Measure: Compliance with treatment Time: It will be evaluated during the five days that the chemoprophylaxis with hydorxychloroquine is administeredDescription: Dichotomous categorical variable. The participant presents symptoms compatible with SARS-CoV-2 infection. High temperature, cephalea, dyspnea,diarrhea, vomiting, arthro-myalgia, pharynx pain, abdominal pain, anosmia, cough.
Measure: Symptoms of SARS-CoV-2 infection at six days Time: This outcome will be evaluated at 6 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable. The participant presents symptoms compatible with SARS-CoV-2 infection. High temperature, cephalea, dyspnea,diarrhea, vomiting, arthro-myalgia, pharynx pain, abdominal pain, anosmia, cough.
Measure: Symptoms of SARS-CoV-2 infection at 14 days Time: This outcome will be evaluated at 14 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable. The participant presents symptoms compatible with SARS-CoV-2 infection. High temperature, cephalea, dyspnea,diarrhea, vomiting, arthro-myalgia, pharynx pain, abdominal pain, anosmia, cough.
Measure: Symptoms of SARS-CoV-2 infection at 28 days Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable. Participant requires hospital admission attributable to SARS-CoV-2 infection
Measure: Hospitalization Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Polycotomic categorical variable. Collected by clinical interview and also monitored simultaneously by external trial monitors
Measure: Adverse events at six days Time: This outcome will be evaluated at six days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Polycotomic categorical variable. Collected by clinical interview and also monitored simultaneously by external trial monitors
Measure: Adverse events at 14 days Time: This outcome will be evaluated at 14 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Polycotomic categorical variable. Collected by clinical interview and also monitored simultaneously by external trial monitors
Measure: Adverse events at 28 days Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquine