Name (Synonyms) | Correlation | |
---|---|---|
drug360 | Hydroxychloroquine Wiki | 0.23 |
drug627 | Placebo oral tablet Wiki | 0.19 |
drug616 | Placebo Wiki | 0.17 |
drug375 | Hydroxychloroquine Sulfate Wiki | 0.16 |
drug46 | Anakinra Wiki | 0.13 |
drug691 | Remdesivir Wiki | 0.13 |
drug558 | No intervention Wiki | 0.12 |
drug634 | Plasma Wiki | 0.12 |
drug92 | BCG Vaccine Wiki | 0.12 |
drug60 | Ascorbic Acid Wiki | 0.12 |
drug771 | Standard of Care Wiki | 0.12 |
drug304 | Favipiravir Wiki | 0.11 |
drug632 | Placebos Wiki | 0.11 |
drug478 | Lopinavir/ritonavir Wiki | 0.11 |
drug480 | Losartan Wiki | 0.11 |
drug230 | Convalescent plasma Wiki | 0.11 |
drug883 | Usual Care Wiki | 0.11 |
drug750 | Single Dose of Hydroxychloroquine Wiki | 0.10 |
drug552 | Nitric Oxide Wiki | 0.10 |
drug364 | Hydroxychloroquine + azithromycin Wiki | 0.10 |
drug656 | Prone positioning Wiki | 0.10 |
drug692 | Remdesivir placebo Wiki | 0.10 |
drug738 | Selinexor Wiki | 0.10 |
drug708 | Ruxolitinib Oral Tablet Wiki | 0.10 |
drug208 | Colchicine Wiki | 0.09 |
drug361 | Hydroxychloroquine (HCQ) Wiki | 0.08 |
drug934 | blood sample Wiki | 0.08 |
drug554 | Nitric Oxide Gas Wiki | 0.08 |
drug901 | Vitamin D Wiki | 0.08 |
drug429 | Interferon Beta-1B Wiki | 0.08 |
drug469 | Lopinavir / Ritonavir Wiki | 0.08 |
drug428 | Interferon Beta-1A Wiki | 0.08 |
drug82 | Azithromycin Wiki | 0.08 |
drug225 | Convalescent Plasma Wiki | 0.07 |
drug378 | Hydroxychloroquine Sulfate + Azythromycin Wiki | 0.07 |
drug906 | Web application users Wiki | 0.07 |
drug93 | BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki | 0.07 |
drug866 | Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule Wiki | 0.07 |
drug166 | CYNK-001 Wiki | 0.07 |
drug633 | Plaquenil 200Mg Tablet Wiki | 0.07 |
drug294 | Examine the impact of COVID-19 during pregnancy Wiki | 0.07 |
drug423 | Inhaled budesonide Wiki | 0.07 |
drug464 | Linagliptin Wiki | 0.07 |
drug667 | Quality of Life Wiki | 0.07 |
drug32 | Additional biological samples Wiki | 0.07 |
drug966 | hyperimmune plasma Wiki | 0.07 |
drug894 | Verapamil Wiki | 0.07 |
drug258 | Dexamethasone Wiki | 0.07 |
drug713 | SARILUMAB Wiki | 0.07 |
drug961 | hydroxychloroquine + azithromycin Wiki | 0.07 |
drug510 | Mid dose chloroquine or hydroxychloroquine Wiki | 0.07 |
drug836 | Thalidomide Wiki | 0.07 |
drug838 | The Vie Scope laryngoscope Wiki | 0.07 |
drug235 | Cordio App Wiki | 0.07 |
drug1017 | samling of oropharynx and nasopharynx Wiki | 0.07 |
drug903 | VivaDiag™ COVID-19 lgM/IgG Rapid Test Wiki | 0.07 |
drug314 | Follow-up at 14 days Wiki | 0.07 |
drug908 | Weekly Assessment Wiki | 0.07 |
drug936 | blood sampling Wiki | 0.07 |
drug194 | Chloroquine diphosphate Wiki | 0.07 |
drug2 | (Standard of Care) SoC Wiki | 0.07 |
drug806 | Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors Wiki | 0.07 |
drug534 | NSS Saline Placebo Wiki | 0.07 |
drug666 | Qualitative interviews (in 40 patients : 20 with COVID-19 and 20 without COVID-19) Wiki | 0.07 |
drug679 | Random Donor Plasma Wiki | 0.07 |
drug348 | High does chloroquine or hydroxychloroquine Wiki | 0.07 |
drug205 | Clopidogrel Wiki | 0.07 |
drug837 | 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 | 0.07 |
drug800 | Supportive Care Wiki | 0.07 |
drug819 | Taste and olfactory function evaluation Wiki | 0.07 |
drug1037 | trimethoprim/sulfamethoxazole Wiki | 0.07 |
drug858 | Toraymyxin PMX-20R (PMX Cartridge) Wiki | 0.07 |
drug976 | mRNA-1273 Wiki | 0.07 |
drug984 | mouthrinse without bêta-cyclodextrin and citrox Wiki | 0.07 |
drug794 | Streptokinase Wiki | 0.07 |
drug326 | Group A HCQ Wiki | 0.07 |
drug452 | Ketamine Wiki | 0.07 |
drug62 | Ascorbic Acid and Zinc Gluconate Wiki | 0.07 |
drug381 | Hydroxychloroquine Sulfate 200 milligram (mg) Tab Wiki | 0.07 |
drug493 | Matched Placebo Wiki | 0.07 |
drug566 | Normal Saline Infusion + Maximal intensive care Wiki | 0.07 |
drug448 | Ivermectin plus Nitazoxanide Wiki | 0.07 |
drug630 | Placebo: Emtricitabine/tenofovir disoproxil Placebo Wiki | 0.07 |
drug277 | Eicosapentaenoic acid gastro-resistant capsules Wiki | 0.07 |
drug717 | SARS-CoV-2 rS Wiki | 0.07 |
drug387 | Hydroxychloroquine Sulfate and Azithromycin Wiki | 0.07 |
drug89 | BAT Wiki | 0.07 |
drug465 | Linagliptin 5 MG Wiki | 0.07 |
drug867 | Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule Wiki | 0.07 |
drug501 | Melatonin 2mg Wiki | 0.07 |
drug983 | mouthrinse with bêta-cyclodextrin and citrox Wiki | 0.07 |
drug792 | Sterile Normal Saline for Intravenous Use Wiki | 0.07 |
drug282 | Emtricitabine/tenofovir disoproxil Wiki | 0.07 |
drug604 | Peginterferon Lambda-1a Wiki | 0.07 |
drug1032 | telehealth applications Wiki | 0.07 |
drug684 | Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki | 0.07 |
drug57 | Apo-Hydroxychloroquine Wiki | 0.07 |
drug544 | New screening strategy Wiki | 0.07 |
drug878 | Umifenovir Wiki | 0.07 |
drug367 | Hydroxychloroquine + placebo Wiki | 0.07 |
drug1041 | vv-ECMO + cytokine adsorption (Cytosorb adsorber) Wiki | 0.07 |
drug590 | PD-1 blocking antibody+standard treatment Wiki | 0.07 |
drug145 | CELLECTRA® 2000 Wiki | 0.07 |
drug354 | Human biological samples Wiki | 0.07 |
drug789 | Standards of Care Wiki | 0.07 |
drug997 | oral nutrition supplement (ONS) enriched in eicosapentaenoic acid, gamma-linolenic acid and antioxidants Wiki | 0.07 |
drug537 | Naltrexone Wiki | 0.07 |
drug973 | lopinavir/ritonavir group Wiki | 0.07 |
drug211 | Collection of samples Wiki | 0.07 |
drug183 | Centricyte 1000 Wiki | 0.07 |
drug351 | Hospital anxiety and depression scale Wiki | 0.07 |
drug395 | Hydroxychloroquine plus standard preventive measures Wiki | 0.07 |
drug937 | captopril 25mg Wiki | 0.07 |
drug403 | Hyperbaric oxygen therapy Wiki | 0.07 |
drug119 | Biological collection (patients co infected HIV Sras-CoV-2) Wiki | 0.07 |
drug408 | INO-4800 Wiki | 0.07 |
drug629 | Placebo solution Wiki | 0.07 |
drug372 | Hydroxychloroquine Oral Product Wiki | 0.07 |
drug841 | There is no intervention in this study Wiki | 0.07 |
drug516 | Monitoring Visit - Week 8 Wiki | 0.07 |
drug877 | Umbilical cord Wharton's jelly-derived human Wiki | 0.07 |
drug79 | Awake Proning Wiki | 0.07 |
drug734 | Satisfaction evaluation Wiki | 0.07 |
drug284 | Enoxaparin Wiki | 0.07 |
drug930 | bidirectional oxygenation mouthpiece Wiki | 0.07 |
drug839 | The standard Macintosh laryngoscope Wiki | 0.07 |
drug140 | Burnout Wiki | 0.07 |
drug475 | Lopinavir and Ritonavir Tablets Wiki | 0.07 |
drug61 | Ascorbic Acid and Folic Acid Wiki | 0.07 |
drug876 | Umbilical Cord Mesenchymal Stem Cells Wiki | 0.07 |
drug380 | Hydroxychloroquine Sulfate 200 MG [Plaquenil] Wiki | 0.07 |
drug621 | Placebo Vaccine Wiki | 0.07 |
drug910 | XPro1595 Wiki | 0.07 |
drug1002 | pirfenidone Wiki | 0.07 |
drug374 | Hydroxychloroquine SAR321068 Wiki | 0.07 |
drug1029 | standard treatment Wiki | 0.07 |
drug1013 | rapid salivary test Wiki | 0.07 |
drug315 | Fondaparinux Wiki | 0.07 |
drug915 | Zinc Wiki | 0.07 |
drug569 | Nutrition support Wiki | 0.07 |
drug154 | COVID-19 convalescent plasma Wiki | 0.07 |
drug373 | Hydroxychloroquine Pre-Exposure Prophylaxis Wiki | 0.07 |
drug227 | Convalescent Plasma Transfusion Wiki | 0.07 |
drug956 | high flow nasal cannula (HFNC) Wiki | 0.07 |
drug1038 | turkish physicians Wiki | 0.07 |
drug427 | Insulin regimen Wiki | 0.07 |
drug916 | Zinc Gluconate Wiki | 0.07 |
drug191 | Chloroquine Diphosphate Wiki | 0.07 |
drug859 | Tradipitant Wiki | 0.07 |
drug472 | Lopinavir / ritonavir tablets combined with Xiyanping injection Wiki | 0.07 |
drug431 | Interferon-Beta Wiki | 0.07 |
drug938 | care modalities Wiki | 0.07 |
drug80 | Ayurveda Wiki | 0.07 |
drug508 | Methylprednisolone Sodium Succinate Wiki | 0.07 |
drug358 | Hydoxychloroquine or Chloroquine Wiki | 0.07 |
drug581 | Oral placebo Wiki | 0.07 |
drug449 | Ivermectine Wiki | 0.07 |
drug90 | BAT + Calcifediol Wiki | 0.07 |
drug416 | Impact Event Score Wiki | 0.07 |
drug415 | Immunological profiling Wiki | 0.07 |
drug215 | Comprehensive treatment Wiki | 0.07 |
drug989 | no intervention Wiki | 0.07 |
drug575 | Odd/Even birth year intervention groups Wiki | 0.07 |
drug436 | Internet-delivered cognitive behavior therapy (ICBT) for dysfunctional worry related to the Covid-19 pandemic Wiki | 0.07 |
drug70 | Association of diltiazem and niclosamide Wiki | 0.07 |
drug868 | Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule Wiki | 0.07 |
drug780 | Standard screening strategy Wiki | 0.07 |
drug54 | Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients Wiki | 0.07 |
drug327 | Group B Control Wiki | 0.07 |
drug567 | Normal saline Wiki | 0.07 |
drug614 | Piclidenoson Wiki | 0.07 |
drug125 | Biosensors Wiki | 0.07 |
drug601 | Patient sampling Wiki | 0.07 |
drug409 | IV Deployment Of cSVF In Sterile Normal Saline IV Solution Wiki | 0.07 |
drug84 | Azithromycin 500 mg Wiki | 0.07 |
drug1026 | standard operating procedures Wiki | 0.07 |
drug715 | SARS-CoV-2 IgG Antibody Testing Kit Wiki | 0.07 |
drug573 | Observational Study Wiki | 0.07 |
drug424 | Inhaled nitric oxide gas Wiki | 0.07 |
drug939 | chlorine dioxide 3000 ppm Wiki | 0.07 |
drug412 | Imatinib Wiki | 0.07 |
drug78 | Aviptadil by intravenous infusion + maximal intensive care Wiki | 0.07 |
drug572 | Observational (registry) Wiki | 0.07 |
drug1011 | questionnair about Emerging Legal and Ehical Disputes Over Patient Confidentiality Wiki | 0.07 |
drug31 | Acetylsalicylic acid Wiki | 0.07 |
drug341 | Health Care Worker Survey Wiki | 0.07 |
drug165 | CT-imaging Wiki | 0.07 |
drug410 | Ibuprofen Wiki | 0.07 |
drug153 | COVID-19 barrier box Wiki | 0.07 |
drug985 | muscle ultrasound Wiki | 0.07 |
drug822 | Teleconsultation either by phone or by computer consultation Wiki | 0.07 |
drug830 | Telmisartan arm will receive 80 mg Telmisartan twice daily plus standard care. Wiki | 0.07 |
drug657 | Prone positioning (PP) Wiki | 0.07 |
drug463 | Liberase Enzyme (Roche) Wiki | 0.07 |
drug861 | Transfusion of COVID-19 convalescent plasma Wiki | 0.07 |
drug971 | laboratory biomarkers Wiki | 0.07 |
drug301 | Extra blood sample Wiki | 0.07 |
drug239 | Cytokine Adsorption Wiki | 0.07 |
drug578 | Online Survey Wiki | 0.07 |
drug988 | newborns from covid 19 positive mothers Wiki | 0.07 |
drug483 | Low-dose chloroquine/hydroxychloroquine Wiki | 0.07 |
drug451 | Kerecis Oral and Nasal Spray Wiki | 0.07 |
drug377 | Hydroxychloroquine Sulfate + Azithromycin Wiki | 0.07 |
drug481 | Low Dose Radiation Therapy Wiki | 0.07 |
drug932 | blood donation SMS Wiki | 0.07 |
drug514 | Monitoring Visit - Baseline Wiki | 0.07 |
drug297 | Experimental: Questionnaire without precaution information Wiki | 0.07 |
drug495 | Matrix-M Adjuvant Wiki | 0.07 |
drug959 | hospitalized children with Covid19 Wiki | 0.07 |
drug305 | Favipiravir + Standard of Care Wiki | 0.07 |
drug804 | Survey and Questionnaire Wiki | 0.07 |
drug854 | Tocilizumab Wiki | 0.07 |
drug426 | Injective placebo Wiki | 0.07 |
drug852 | To assess for development of IgG antibodies against SARS-CoV2 Wiki | 0.07 |
drug902 | Vitamins Wiki | 0.07 |
drug471 | Lopinavir / Ritonavir plus Ribavirin Wiki | 0.07 |
drug252 | Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days Wiki | 0.07 |
drug515 | Monitoring Visit - Week 4 Wiki | 0.07 |
drug353 | Human Biological samples Wiki | 0.07 |
drug274 | EUROIMMUN assay Wiki | 0.07 |
drug588 | Oxygen-ozone therapy, probiotic supplementation and Standard of care Wiki | 0.07 |
drug798 | Study Group Wiki | 0.07 |
drug869 | Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule Wiki | 0.07 |
drug843 | Thoracic CT Scan Wiki | 0.07 |
drug751 | Sirolimus 1 MG/ML Wiki | 0.07 |
drug829 | Telmisartan 40mg Wiki | 0.07 |
drug36 | Alferon LDO Wiki | 0.07 |
drug24 | ASC09/ritonavir group Wiki | 0.07 |
drug278 | Electric pad for human external pain therapy Wiki | 0.07 |
drug44 | Amiodarone Wiki | 0.07 |
drug95 | BLD-2660 Wiki | 0.07 |
drug368 | Hydroxychloroquine - Daily Dosing Wiki | 0.07 |
drug41 | Alteplase 50 MG [Activase] Wiki | 0.07 |
drug388 | Hydroxychloroquine Sulfate and Folic Acid Wiki | 0.07 |
drug870 | Two doses of placebo at the emergency vaccination schedule Wiki | 0.07 |
drug698 | Ribavirin Wiki | 0.07 |
drug352 | Huaier Granule Wiki | 0.07 |
drug51 | Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) Wiki | 0.07 |
drug631 | Placebo: Hydroxychloroquine Wiki | 0.07 |
drug879 | Unfractionated heparin Wiki | 0.07 |
drug676 | REGN3051 Wiki | 0.07 |
drug338 | HOME-CoV rule implementation Wiki | 0.07 |
drug921 | all treatment about COVID-2019 Wiki | 0.07 |
drug670 | Questionnaire with precaution information Wiki | 0.07 |
drug849 | Thymosin+standard treatment Wiki | 0.07 |
drug733 | Sarilumab SAR153191 Wiki | 0.07 |
drug749 | Simvastatin Wiki | 0.07 |
drug675 | REGN3048 Wiki | 0.07 |
drug147 | COPAN swabbing and blood sample collection Wiki | 0.07 |
drug744 | Serum test Wiki | 0.07 |
drug619 | Placebo 250 cc 24 hours continuous infusion for 15 days Wiki | 0.07 |
drug1014 | recombinant human interferon Alpha-1b Wiki | 0.07 |
drug49 | Angiotensin 1-7 Wiki | 0.07 |
drug741 | Serological test Wiki | 0.07 |
drug350 | Honey Wiki | 0.07 |
drug432 | Interferon-β 1a Wiki | 0.07 |
drug970 | isocaloric/isonutrigenous ONS Wiki | 0.07 |
drug637 | Point-of-Care Ultrasonography (POCUS) Wiki | 0.07 |
drug919 | a specifically designed self-administered questionnaire Wiki | 0.07 |
drug74 | Auto-questionnaires (patients co infected HIV Sras-CoV-2) Wiki | 0.07 |
drug67 | Assessment of Dietary Changes in Adults in the Quarantine Wiki | 0.07 |
drug535 | NaCl 0.9% Wiki | 0.07 |
drug112 | Best Available Therapy Wiki | 0.07 |
drug1028 | standard therapy Wiki | 0.07 |
drug418 | Individualised Ayurveda Wiki | 0.07 |
drug825 | Telephone survey Wiki | 0.07 |
drug645 | Powered Air purifying respirator Wiki | 0.07 |
drug564 | Non-convalescent Plasma (control plasma) Wiki | 0.07 |
drug1006 | prayer Wiki | 0.07 |
drug628 | Placebo plus standard preventive measures Wiki | 0.07 |
drug334 | HCQ + Intravenous Famotidine Wiki | 0.07 |
drug229 | Convalescent anti-SARS-CoV-2 plasma Wiki | 0.07 |
drug778 | Standard of care treatment Wiki | 0.07 |
drug791 | Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki | 0.07 |
drug696 | Retrospective data collection Wiki | 0.07 |
drug967 | iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System Wiki | 0.07 |
drug871 | Two doses of placebo at the routine vaccination schedule Wiki | 0.07 |
drug321 | Gargle/Mouthwash Wiki | 0.07 |
drug53 | Anti-Sars-CoV-2 Convalescent Plasma Wiki | 0.07 |
drug37 | Allogeneic NK transfer Wiki | 0.07 |
drug776 | Standard of care (SOC) Wiki | 0.07 |
drug1015 | remdesivir Wiki | 0.07 |
drug73 | Auricular neuromodulation Wiki | 0.07 |
drug164 | CT-V Wiki | 0.07 |
drug596 | PTSD Wiki | 0.07 |
drug457 | Lactated ringer's solution or sterile saline Wiki | 0.07 |
drug598 | Pacebo: Calcium citrate Wiki | 0.07 |
drug63 | Aspirin Wiki | 0.07 |
drug402 | Hyperbaric oxygen Wiki | 0.07 |
drug226 | Convalescent Plasma (anti-SARS-CoV-2 plasma) Wiki | 0.07 |
drug602 | Patients with the treatment agains COVID19 Wiki | 0.07 |
drug339 | Halo Oral Spray Wiki | 0.07 |
drug342 | Helmet non-invasive ventilation (NIV) Wiki | 0.07 |
drug710 | Ruxolitinib plus simvastatin Wiki | 0.07 |
drug905 | WJ-MSCs Wiki | 0.07 |
drug719 | SARS-Cov-2 infection Wiki | 0.07 |
drug291 | Escin Wiki | 0.07 |
drug376 | Hydroxychloroquine Sulfate (HCQ) Wiki | 0.07 |
drug568 | Normobaric oxygen therapy Wiki | 0.07 |
drug550 | Nitazoxanide 500 MG Wiki | 0.07 |
drug851 | Tirofiban Injection Wiki | 0.07 |
drug553 | Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki | 0.07 |
drug40 | Alteplase 100 MG [Activase] Wiki | 0.07 |
drug335 | HCQ + Placebo Wiki | 0.07 |
drug1036 | thymosin alpha 1 Wiki | 0.07 |
drug296 | Experimental drug Wiki | 0.07 |
drug547 | Nigella Sativa / Black Cumin Wiki | 0.07 |
drug479 | Lopinavir/ritonavir treatment Wiki | 0.07 |
drug509 | Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF) Wiki | 0.07 |
drug964 | hydroxychloroquine sulfate 200 MG Wiki | 0.07 |
drug273 | ECG Wiki | 0.07 |
drug340 | Halo Placebo Wiki | 0.07 |
drug379 | Hydroxychloroquine Sulfate 200 MG Wiki | 0.07 |
drug803 | Survey Wiki | 0.07 |
drug1042 | vv-ECMO only (no cytokine adsorption) Wiki | 0.07 |
drug445 | Isotretinoin Only Product in Oral Dose Form Wiki | 0.07 |
drug333 | HCQ & AZ Wiki | 0.07 |
drug707 | Ruxolitinib Wiki | 0.06 |
drug900 | Vitamin C Wiki | 0.06 |
drug190 | Chloroquine Wiki | 0.06 |
drug732 | Sarilumab Wiki | 0.06 |
drug671 | Questionnaires Wiki | 0.05 |
drug533 | NORS (Nitric Oxide Releasing Solution) Wiki | 0.05 |
drug117 | Bevacizumab Injection Wiki | 0.05 |
drug107 | Baricitinib Wiki | 0.05 |
drug455 | L-ascorbic acid Wiki | 0.05 |
drug946 | convalescent plasma Wiki | 0.05 |
drug752 | SivoMixx (200 billion) Wiki | 0.05 |
drug828 | Telmisartan Wiki | 0.05 |
drug995 | observational Wiki | 0.05 |
drug538 | Nasal swab Wiki | 0.05 |
drug762 | Standard Care Wiki | 0.05 |
drug87 | Azithromycin Tablets Wiki | 0.05 |
drug557 | No Intervention Wiki | 0.05 |
drug370 | Hydroxychloroquine - Weekly Dosing Wiki | 0.05 |
drug748 | Siltuximab Wiki | 0.05 |
drug644 | Povidone-Iodine Nasal Spray and Gargle Wiki | 0.05 |
drug317 | GLS-5300 Wiki | 0.05 |
drug386 | Hydroxychloroquine Sulfate Regular dose Wiki | 0.05 |
drug58 | Arbidol Wiki | 0.05 |
drug579 | Online questionnaire Wiki | 0.05 |
drug1018 | self-administered questionnaire Wiki | 0.05 |
drug1023 | standard care Wiki | 0.05 |
drug152 | COVID-19 Serology Wiki | 0.05 |
drug540 | Nasopharyngeal swab Wiki | 0.05 |
drug130 | Blood draw Wiki | 0.05 |
drug799 | Sulfonated tetra-anthracenyl porphyrin Wiki | 0.05 |
drug313 | Follow up Wiki | 0.05 |
drug192 | Chloroquine Sulfate Wiki | 0.05 |
drug330 | HB-adMSCs Wiki | 0.05 |
drug385 | Hydroxychloroquine Sulfate Loading Dose Wiki | 0.05 |
drug925 | anti-SARS-CoV-2 convalescent plasma Wiki | 0.04 |
drug169 | Camostat Mesilate Wiki | 0.04 |
drug960 | hydroxychloroquine Wiki | 0.04 |
drug220 | Control Wiki | 0.04 |
drug668 | Questionnaire Wiki | 0.04 |
drug753 | SnPP Protoporphyrin Wiki | 0.03 |
drug1003 | placebo Wiki | 0.03 |
drug507 | Methylprednisolone Wiki | 0.02 |
drug775 | Standard of care Wiki | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
D018352 | Coronavirus Infections NIH | 0.79 |
D014777 | Virus Diseases NIH | 0.41 |
D007239 | Infection NIH | 0.36 |
D003141 | Communicable Diseases NIH | 0.35 |
D013577 | Syndrome NIH | 0.24 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.19 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.19 |
D055371 | Acute Lung Injury NIH | 0.18 |
D011014 | Pneumonia NIH | 0.18 |
D011024 | Pneumonia, Viral NIH | 0.17 |
D003333 | Coronaviridae Infections NIH | 0.12 |
D058070 | Asymptomatic Diseases NIH | 0.10 |
D012327 | RNA Virus Infections NIH | 0.10 |
D013313 | Stress Disorders, Post-Traumatic NIH | 0.10 |
D012141 | Respiratory Tract Infections NIH | 0.09 |
D003924 | Diabetes Mellitus, Type 2 NIH | 0.08 |
D016638 | Critical Illness NIH | 0.07 |
D006470 | Hemorrhage NIH | 0.07 |
D008659 | Metabolic Diseases NIH | 0.07 |
D006929 | Hyperaldosteronism NIH | 0.07 |
D003428 | Cross Infection NIH | 0.07 |
D014552 | Urinary Tract Infections NIH | 0.07 |
D004700 | Endocrine System Diseases NIH | 0.07 |
D054990 | Idiopathic Pulmonary Fibrosis NIH | 0.07 |
D000309 | Adrenal Insufficiency NIH | 0.07 |
D012772 | Shock, Septic NIH | 0.07 |
D054559 | Hyperphosphatemia NIH | 0.07 |
D007154 | Immune System Diseases NIH | 0.07 |
D011649 | Pulmonary Alveolar Proteinosis NIH | 0.07 |
D007008 | Hypokalemia NIH | 0.07 |
D019446 | Endotoxemia NIH | 0.07 |
D019851 | Thrombophilia NIH | 0.07 |
D040921 | Stress Disorders, Traumatic NIH | 0.07 |
D016769 | Embolism and Thrombosis NIH | 0.07 |
D018805 | Sepsis NIH | 0.07 |
D004617 | Embolism NIH | 0.07 |
D008171 | Lung Diseases, NIH | 0.07 |
D001997 | Bronchopulmonary Dysplasia NIH | 0.07 |
D011565 | Psoriasis NIH | 0.07 |
D055501 | Macrophage Activation Syndrome NIH | 0.07 |
D009220 | Myositis NIH | 0.07 |
D044882 | Glucose Metabolism Disorders NIH | 0.07 |
D008595 | Menorrhagia NIH | 0.07 |
D009205 | Myocarditis NIH | 0.07 |
D012140 | Respiratory Tract Diseases NIH | 0.05 |
D030341 | Nidovirales Infections NIH | 0.05 |
D003139 | Common Cold NIH | 0.05 |
D000860 | Hypoxia NIH | 0.05 |
D011658 | Pulmonary Fibrosis NIH | 0.04 |
D011665 | Pulmonary Valve Insufficiency NIH | 0.04 |
D029424 | Pulmonary Disease, Chronic Obstructive NIH | 0.04 |
D004417 | Dyspnea NIH | 0.04 |
D003920 | Diabetes Mellitus, NIH | 0.04 |
D017563 | Lung Diseases, Interstitial NIH | 0.04 |
D012769 | Shock, NIH | 0.04 |
D008173 | Lung Diseases, Obstructive NIH | 0.04 |
D007249 | Inflammation NIH | 0.03 |
D006973 | Hypertension NIH | 0.03 |
D058186 | Acute Kidney Injury NIH | 0.03 |
D013927 | Thrombosis NIH | 0.03 |
D018450 | Disease Progression NIH | 0.03 |
D007251 | Influenza, Human NIH | 0.03 |
D053717 | Pneumonia, Ventilator-Associated NIH | 0.03 |
D004630 | Emergencies NIH | 0.02 |
D055370 | Lung Injury NIH | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0002090 | Pneumonia HPO | 0.08 |
HP:0000132 | Menorrhagia HPO | 0.07 |
HP:0002900 | Hypokalemia HPO | 0.07 |
HP:0000859 | Hyperaldosteronism HPO | 0.07 |
HP:0010444 | Pulmonary insufficiency HPO | 0.07 |
HP:0000846 | Adrenal insufficiency HPO | 0.07 |
HP:0002791 | Hypoventilation HPO | 0.07 |
HP:0000822 | Hypertension HPO | 0.05 |
HP:0002098 | Respiratory distress HPO | 0.05 |
There are 202 clinical trials
This 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 daysSevere 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 daysThis study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Measure: Time to recovery Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Change in National Early Warning Score (NEWS) from baseline Time: Day 1 through Day 29Description: 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 - 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: Clinical status using ordinal scale Time: Day 3 through Day 29Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs) Time: Day 1 through Day 29Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measure: Cumulative incidence of serious adverse events (SAEs) Time: Day 1 through Day 29Description: For any reason.
Measure: Discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: 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 - 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: Mean change in the ordinal scale Time: Day 1 through Day 29Description: 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 - 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: Percentage of subjects reporting each severity rating on an 8-point ordinal scale Time: Day 15Description: Date and cause of death (if applicable).
Measure: Subject 14-day mortality Time: Day 1 through Day 15Description: Date and cause of death (if applicable).
Measure: Subject 29-day mortality Time: Day 1 through Day 29Description: 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 - 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: Time to an improvement of one category using an ordinal scale Time: Day 1 through Day 29Description: 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 - 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: Time to an improvement of two categories using an ordinal scale Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Time to discharge or to a National Early Warning Score (NEWS) of = 2 and maintained for 24 hours, whichever occurs first Time: Day 1 through Day 29Since 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 weeksThis is a phase I, open-label, dose ranging clinical trial in males and non-pregnant females, 18 to 55 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity and immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc. mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike (S) protein of SARS-CoV-2. Enrollment will occur at one domestic site. Forty-five subjects will be enrolled into one of three cohorts and will receive an intramuscular (IM) injection of mRNA-1273 on Days 1 and 29 in the deltoid muscle. Subjects will be followed through 12 months post second vaccination (Day 394). The primary objective is to evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 3 dosages in healthy adults.
Description: Seroconversion is defined as a 4-fold change in antibody titer from baseline
Measure: Percentage of subjects who seroconverted Time: Day 1 to Day 57The 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 6 points. Alive at home 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 6 points. Alive at home 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: Positive PCR for Sars-Cov-2 at 10 days after enrollment
Measure: Presence of virus at day 10 in subset of 180 patients Time: 10 days after randomizationDescription: QTc interval value
Measure: Safety outcome on QTc 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 monthsOpen label, two-group, phase III randomised controlled trial in up to 4170 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 fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
Measure: COVID-19 disease incidence Time: Measured over the 6 months following randomisationDescription: Number of participants who were admitted to hospital or died (using self-reported questionnaire and/or medical/hospital records) in the context of a positive SARS-CoV-2 test
Measure: Severe COVID-19 disease incidence Time: Measured over the 6 months following randomisationDescription: Number of participants with COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
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 hospitalisation or death in the context of a positive SARS-Cov-2 test (PCR or serology)
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: fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
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 fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
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 fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
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 fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
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: fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)
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 febrile respiratory illness defined as fever (using self-reported questionnaire), plus 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: Febrile respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of episodes of febrile respiratory illness, defined as fever (using self-reported questionnaire), plus 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 febrile 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 febrile respiratory illness defined as fever (using self-reported questionnaire), plus 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 febrile respiratory illness Time: Measured over the 12 months following randomisationDescription: Number of days confined to bed (using self-reported questionnaire) due to febrile respiratory illness defined as fever (using self-reported questionnaire), plus 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 febrile 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 febrile respiratory illness: fever (using self-reported questionnaire), plus 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 febrile 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 febrile respiratory illness (using self-reported questionnaire and/or medical/hospital records)
Measure: Hospitalisation duration with febrile 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 reported in Australian dollars (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 Objectives: Phase 2: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe COVID-19 Phase 3: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe or critical COVID-19 Secondary Objectives: Phase 2 and Phase 3 - 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) - Evaluate the 28-day mortality rate - 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) - Grade 4 neutropenia (ANC<500/mmˆ3) with concurrent severe or life-threatening bacterial, invasive fungal, or opportunistic infection - 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) - Invasive bacterial or fungal infections of clinical significance with confirmed diagnosis based on the investigator's assessment with appropriate diagnostic workups and consultations
Description: Resolution of fever is defined as body temperature: ≤36.6 C (axilla) or ≤37.2 C (oral), or ≤37.8 C (rectal or tympanic).
Measure: Phase 2: Time to resolution of fever for at least 48 hours without antipyretics or until discharge, whichever is sooner Time: Baseline to Day 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 3: The percentage of patients reporting each severity rating on the 7-point ordinal scale Time: Baseline to Day 15Description: Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
Measure: Phase 2: The time to improvement in oxygenation Time: Baseline to Day 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 2: Mean change in 7-point ordinal scale from baseline to Day 15 Time: Baseline to Day 15Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 2: Clinical status using the 7-point ordinal scale at Day 15 Time: Baseline to Day 15Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 2: Time to improvement of two categories from admission using the 7-point ordinal scale Time: Baseline to Day 29Description: 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: Phase 2 and 3 : Time to resolution of fever Time: Baseline to Day 29Description: Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2) for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
Measure: Phase 2 and 3 : Time to improvement in oxygenation 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 increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2) for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
Measure: Phase 2 and 3: Time to resolution of fever and improvement in oxygenation 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: Phase 2 and 3: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: Phase 2 and 3: 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: Phase 2 and 3: Mean change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS2 Time: Baseline to days 3, 5, 8, 11, 15, and 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 period.
Measure: Phase 2 and 3:Days with fever 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: Phase 2 and 3: Alive off supplemental oxygen at day 29 Time: Baseline to Day 29Description: Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.
Measure: Phase 2 and 3: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: Phase 2 and 3: Days of supplemental oxygen use Time: Baseline to Day 29Description: For those not requiring these interventions at baseline.
Measure: Phase 2 and 3: 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: Phase 2 and 3: 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 60Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 3: Mean change in the 7-point ordinal scale from baseline to days 3, 5, 8, 11, 15, and 29 (or until discharge) Time: baseline to days 3, 5, 8, 11, 15, and 29 (or until discharge)Description: The ordinal scale is an assessment of the clinical status. Scores range 1-7. Lower score is worse.
Measure: Phase 3: Clinical status using the 7-point ordinal scale at days 3, 5, 8, 11,15, and 29 Time: Days 3, 5, 8, 11,15, and 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Phase 3: Time to improvement of two categories from admission using the 7-point ordinal scale Time: Baseline to Day 29The 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 60 patients, of whom 20 will be cell-treated while the remaining 40 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 Méary 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 monthThe 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 interventionThe 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 Metro Detroit, 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: 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: Reduction in the number of COVID-19 infections in healthcare workers. 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 daysSARS-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 patients with severe COVID-19 compared to placebo.
Description: The ViVi or Vienna Vaccine Safety Initiative Disease Severity Score ranges from 0 to 22 with the disease severity indicated by increasing score. It is used to score disease severity and risk in patients with influenza-like illness and/or other forms of acute respiratory infections (e.g. RSV, adenovirus metapneumovirus, rhinovirus and other respiratory viral pathogens), including in infants and children. The Investigator will ask yes/no questions to the patient, and the mobile application will automatically calculate the score.
Measure: Change in Vienna Vaccine Safety Initiative (ViVI) Disease Severity Score Time: Up to Day 28The 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: 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 yearsCOVID-19 infection is a respiratory infectious disease caused by a virus called SARS-CoV-2 . This virus is transmitted from person to person through close contacts or respiratory droplets. Symptoms usually start 4 or 5 days after exposure. Some common symptoms include fever, dry cough, feeling tired, muscle aches, and trouble breathing. Although it may affect all organs in our body, it mainly attacks our lungs' ability to help us breathe. There are currently no FDA approved medications to treat COVID-19 infection. Patients are given medications to help alleviate the symptoms. When patients are admitted to the hospital, they are given medications to reduce fever, relieve pain and supplement oxygen. In severe cases, patients are put on a ventilator, a machine designed to to support the lungs. There are a number of drugs undergoing clinical study to see if they are effective in treating the COVID-19 virus. At Maimonides Medical Center, the investigators are taking the appropriate steps to find an effective treatment for COVID-19. The COMBAT COVID-19 Pilot Study is designed for patients diagnosed with COVID-19 infection who require oxygen supplementation to be treated with colchicine to reduce the chance of needing a mechanical ventilator. Colchicine is an FDA approved medication that is used to treat inflammatory disorders such as Gout and Familial Mediterranean Fever. It has also been used to treat other inflammatory conditions such as inflammation around the heart and been demonstrated to help patients who have had an acute heart attack. Colchicine is a readily available drug which is usually well tolerated by patients. The investigators believe that colchicine may reduce the inflammation in the lungs. If so, the lungs may be able heal at a quicker pace and we hope that this may reduce the need for mechanical ventilation. The research will be a randomized trial, patient will be randomly selected to be in either the colchicine treatment group or the standard medicines group. The treatment group will receive colchicine for 14 days or until the day of discharge. The standard medicines group will receive the usual medical therapy as determined by attending physician.
Description: Percentage of patients requiring escalation of supplemental oxygen beyond low-flow nasal cannula (.8L/min)
Measure: Percentage of Patients requiring supplemental oxygen Time: 1 day to 1 monthThis 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: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR
Measure: Rate of 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 fever
Measure: Time to Clinical Improvement of fever 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 achieved clinical improvement of fever
Measure: Rate of Clinical Improvement of fever 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 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: 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 achieve pulmonary clearance
Measure: Rate of Pulmonary Clearance Time: Up to 28 daysDescription: 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: 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 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. We expect the outcomes to 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 days