Name (Synonyms) | Correlation | |
---|---|---|
drug616 | Placebo Wiki | 0.27 |
drug360 | Hydroxychloroquine Wiki | 0.20 |
drug627 | Placebo oral tablet Wiki | 0.15 |
drug558 | No intervention Wiki | 0.14 |
drug691 | Remdesivir Wiki | 0.14 |
drug632 | Placebos Wiki | 0.13 |
drug771 | Standard of Care Wiki | 0.13 |
drug707 | Ruxolitinib Wiki | 0.13 |
drug375 | Hydroxychloroquine Sulfate Wiki | 0.12 |
drug478 | Lopinavir/ritonavir Wiki | 0.12 |
drug883 | Usual Care Wiki | 0.11 |
drug46 | Anakinra Wiki | 0.11 |
drug225 | Convalescent Plasma Wiki | 0.10 |
drug854 | Tocilizumab Wiki | 0.10 |
drug634 | Plasma Wiki | 0.10 |
drug92 | BCG Vaccine Wiki | 0.10 |
drug60 | Ascorbic Acid Wiki | 0.10 |
drug304 | Favipiravir Wiki | 0.09 |
drug480 | Losartan Wiki | 0.08 |
drug1003 | placebo Wiki | 0.08 |
drug230 | Convalescent plasma Wiki | 0.08 |
drug826 | Telerehabilitation Wiki | 0.08 |
drug750 | Single Dose of Hydroxychloroquine Wiki | 0.08 |
drug552 | Nitric Oxide Wiki | 0.08 |
drug762 | Standard Care Wiki | 0.08 |
drug557 | No Intervention Wiki | 0.08 |
drug364 | Hydroxychloroquine + azithromycin Wiki | 0.08 |
drug656 | Prone positioning Wiki | 0.08 |
drug396 | Hydroxychloroquine sulfate Wiki | 0.08 |
drug1016 | retrospective analysis Wiki | 0.08 |
drug692 | Remdesivir placebo Wiki | 0.08 |
drug738 | Selinexor Wiki | 0.08 |
drug579 | Online questionnaire Wiki | 0.08 |
drug1023 | standard care Wiki | 0.08 |
drug775 | Standard of care Wiki | 0.08 |
drug130 | Blood draw Wiki | 0.08 |
drug708 | Ruxolitinib Oral Tablet Wiki | 0.08 |
drug460 | Leronlimab (700mg) Wiki | 0.08 |
drug184 | ChAdOx1 MERS Wiki | 0.08 |
drug195 | Chloroquine or Hydroxychloroquine Wiki | 0.08 |
drug208 | Colchicine Wiki | 0.08 |
drug900 | Vitamin C Wiki | 0.08 |
drug732 | Sarilumab Wiki | 0.07 |
drug361 | Hydroxychloroquine (HCQ) Wiki | 0.06 |
drug925 | anti-SARS-CoV-2 convalescent plasma Wiki | 0.06 |
drug934 | blood sample Wiki | 0.06 |
drug554 | Nitric Oxide Gas Wiki | 0.06 |
drug901 | Vitamin D Wiki | 0.06 |
drug429 | Interferon Beta-1B Wiki | 0.06 |
drug469 | Lopinavir / Ritonavir Wiki | 0.06 |
drug428 | Interferon Beta-1A Wiki | 0.06 |
drug82 | Azithromycin Wiki | 0.06 |
drug674 | RBA-2 Wiki | 0.06 |
drug570 | Observation of behavior and COVID-19 infection will be conducted. Wiki | 0.06 |
drug378 | Hydroxychloroquine Sulfate + Azythromycin Wiki | 0.06 |
drug906 | Web application users Wiki | 0.06 |
drug860 | Traditional Chinese Medicine Prescription Wiki | 0.06 |
drug55 | Antibody-Rich Plasma from COVID-19 recovered patients Wiki | 0.06 |
drug93 | BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki | 0.06 |
drug523 | MuscleSound Ultrasound Wiki | 0.06 |
drug866 | Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule Wiki | 0.06 |
drug166 | CYNK-001 Wiki | 0.06 |
drug633 | Plaquenil 200Mg Tablet Wiki | 0.06 |
drug933 | blood draw Wiki | 0.06 |
drug294 | Examine the impact of COVID-19 during pregnancy Wiki | 0.06 |
drug423 | Inhaled budesonide Wiki | 0.06 |
drug730 | Sampling salivary Wiki | 0.06 |
drug464 | Linagliptin Wiki | 0.06 |
drug832 | Tested for SARS-CoV-2 (regardless of the result) Wiki | 0.06 |
drug667 | Quality of Life Wiki | 0.06 |
drug32 | Additional biological samples Wiki | 0.06 |
drug966 | hyperimmune plasma Wiki | 0.06 |
drug992 | non-RAS blocking antihypertensives Wiki | 0.06 |
drug609 | Personalized health education Wiki | 0.06 |
drug894 | Verapamil Wiki | 0.06 |
drug258 | Dexamethasone Wiki | 0.06 |
drug713 | SARILUMAB Wiki | 0.06 |
drug961 | hydroxychloroquine + azithromycin Wiki | 0.06 |
drug510 | Mid dose chloroquine or hydroxychloroquine Wiki | 0.06 |
drug836 | Thalidomide Wiki | 0.06 |
drug838 | The Vie Scope laryngoscope Wiki | 0.06 |
drug658 | Prospective oberservational registry Wiki | 0.06 |
drug137 | Bromhexine Hydrochloride Tablets Wiki | 0.06 |
drug528 | NA (no intervention) Wiki | 0.06 |
drug235 | Cordio App Wiki | 0.06 |
drug1017 | samling of oropharynx and nasopharynx Wiki | 0.06 |
drug903 | VivaDiag™ COVID-19 lgM/IgG Rapid Test Wiki | 0.06 |
drug863 | Treatment and prophylaxis Wiki | 0.06 |
drug314 | Follow-up at 14 days Wiki | 0.06 |
drug462 | Levamisole and Isoprinosine Wiki | 0.06 |
drug908 | Weekly Assessment Wiki | 0.06 |
drug289 | Equipment with smartwatch throughout hospital stay on the general ward Wiki | 0.06 |
drug948 | conventional management of patients Wiki | 0.06 |
drug936 | blood sampling Wiki | 0.06 |
drug706 | Routine care for COVID-19 patients Wiki | 0.06 |
drug194 | Chloroquine diphosphate Wiki | 0.06 |
drug2 | (Standard of Care) SoC Wiki | 0.06 |
drug806 | Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors Wiki | 0.06 |
drug534 | NSS Saline Placebo Wiki | 0.06 |
drug612 | Physical Therapy Wiki | 0.06 |
drug666 | Qualitative interviews (in 40 patients : 20 with COVID-19 and 20 without COVID-19) Wiki | 0.06 |
drug679 | Random Donor Plasma Wiki | 0.06 |
drug394 | Hydroxychloroquine plus Nitazoxanide Wiki | 0.06 |
drug801 | Surgery Wiki | 0.06 |
drug174 | Candesartan Wiki | 0.06 |
drug348 | High does chloroquine or hydroxychloroquine Wiki | 0.06 |
drug527 | N95 respirator Wiki | 0.06 |
drug205 | Clopidogrel Wiki | 0.06 |
drug453 | Ketogenic diet Wiki | 0.06 |
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 | 0.06 |
drug800 | Supportive Care Wiki | 0.06 |
drug636 | Plasma Donation Wiki | 0.06 |
drug220 | Control Wiki | 0.06 |
drug1010 | quesionnair Wiki | 0.06 |
drug587 | Oxygen Therapy Wiki | 0.06 |
drug819 | Taste and olfactory function evaluation Wiki | 0.06 |
drug1037 | trimethoprim/sulfamethoxazole Wiki | 0.06 |
drug458 | Leflunomide Wiki | 0.06 |
drug848 | Thromboprophylaxis Wiki | 0.06 |
drug858 | Toraymyxin PMX-20R (PMX Cartridge) Wiki | 0.06 |
drug711 | SAB-301 Wiki | 0.06 |
drug976 | mRNA-1273 Wiki | 0.06 |
drug459 | Lenzilumab Wiki | 0.06 |
drug1040 | vaccine candidate MVA-MERS-S Wiki | 0.06 |
drug984 | mouthrinse without bêta-cyclodextrin and citrox Wiki | 0.06 |
drug794 | Streptokinase Wiki | 0.06 |
drug586 | Oxygen Wiki | 0.06 |
drug326 | Group A HCQ Wiki | 0.06 |
drug452 | Ketamine Wiki | 0.06 |
drug62 | Ascorbic Acid and Zinc Gluconate Wiki | 0.06 |
drug381 | Hydroxychloroquine Sulfate 200 milligram (mg) Tab Wiki | 0.06 |
drug493 | Matched Placebo Wiki | 0.06 |
drug566 | Normal Saline Infusion + Maximal intensive care Wiki | 0.06 |
drug448 | Ivermectin plus Nitazoxanide Wiki | 0.06 |
drug630 | Placebo: Emtricitabine/tenofovir disoproxil Placebo Wiki | 0.06 |
drug277 | Eicosapentaenoic acid gastro-resistant capsules Wiki | 0.06 |
drug115 | Best standard of care Wiki | 0.06 |
drug717 | SARS-CoV-2 rS Wiki | 0.06 |
drug387 | Hydroxychloroquine Sulfate and Azithromycin Wiki | 0.06 |
drug89 | BAT Wiki | 0.06 |
drug465 | Linagliptin 5 MG Wiki | 0.06 |
drug867 | Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule Wiki | 0.06 |
drug501 | Melatonin 2mg Wiki | 0.06 |
drug983 | mouthrinse with bêta-cyclodextrin and citrox Wiki | 0.06 |
drug792 | Sterile Normal Saline for Intravenous Use Wiki | 0.06 |
drug282 | Emtricitabine/tenofovir disoproxil Wiki | 0.06 |
drug497 | Medical Mask Wiki | 0.06 |
drug502 | MenACWY Wiki | 0.06 |
drug604 | Peginterferon Lambda-1a Wiki | 0.06 |
drug1032 | telehealth applications Wiki | 0.06 |
drug754 | Social media & news consumption Wiki | 0.06 |
drug684 | Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki | 0.06 |
drug57 | Apo-Hydroxychloroquine Wiki | 0.06 |
drug702 | Rivaroxaban Wiki | 0.06 |
drug1001 | pathogen reduced SARS-CoV-2 convalescent plasma Wiki | 0.06 |
drug565 | Normal (9%) Saline Wiki | 0.06 |
drug544 | New screening strategy Wiki | 0.06 |
drug878 | Umifenovir Wiki | 0.06 |
drug461 | Levamisole Wiki | 0.06 |
drug817 | TJ003234 Wiki | 0.06 |
drug203 | Clinical diagnosis of COVID-19 by a health care professional Wiki | 0.06 |
drug367 | Hydroxychloroquine + placebo Wiki | 0.06 |
drug1041 | vv-ECMO + cytokine adsorption (Cytosorb adsorber) Wiki | 0.06 |
drug108 | Baricitinib (janus kinase inhibitor) Wiki | 0.06 |
drug678 | Ramipril 2.5 MG Oral Capsule Wiki | 0.06 |
drug531 | NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells Wiki | 0.06 |
drug590 | PD-1 blocking antibody+standard treatment Wiki | 0.06 |
drug145 | CELLECTRA® 2000 Wiki | 0.06 |
drug354 | Human biological samples Wiki | 0.06 |
drug694 | Remestemcel-L® Wiki | 0.06 |
drug789 | Standards of Care Wiki | 0.06 |
drug997 | oral nutrition supplement (ONS) enriched in eicosapentaenoic acid, gamma-linolenic acid and antioxidants Wiki | 0.06 |
drug891 | Vazegepant (BHV-3500) Wiki | 0.06 |
drug537 | Naltrexone Wiki | 0.06 |
drug520 | Multifrequency Bioimpedance Spectroscopy Wiki | 0.06 |
drug973 | lopinavir/ritonavir group Wiki | 0.06 |
drug257 | Determination of physical activity, quality of life, stress levels of isolated people at home with the danger of coronavirus. Wiki | 0.06 |
drug211 | Collection of samples Wiki | 0.06 |
drug551 | Nitazoxanide Tablets Wiki | 0.06 |
drug265 | Discontinuation of ARB/ACEI Wiki | 0.06 |
drug183 | Centricyte 1000 Wiki | 0.06 |
drug351 | Hospital anxiety and depression scale Wiki | 0.06 |
drug395 | Hydroxychloroquine plus standard preventive measures Wiki | 0.06 |
drug937 | captopril 25mg Wiki | 0.06 |
drug403 | Hyperbaric oxygen therapy Wiki | 0.06 |
drug119 | Biological collection (patients co infected HIV Sras-CoV-2) Wiki | 0.06 |
drug649 | Pregnant women under investigation for Coronavirus or diagnosed with COVID-19 Wiki | 0.06 |
drug408 | INO-4800 Wiki | 0.06 |
drug629 | Placebo solution Wiki | 0.06 |
drug357 | Humanistic Care Wiki | 0.06 |
drug954 | favipiravir tablets+chloroquine phosphatetablets tablets Wiki | 0.06 |
drug372 | Hydroxychloroquine Oral Product Wiki | 0.06 |
drug841 | There is no intervention in this study Wiki | 0.06 |
drug516 | Monitoring Visit - Week 8 Wiki | 0.06 |
drug898 | Views and experiences of health care professionals working in intensive care units during the COVID-19 pandemic Wiki | 0.06 |
drug842 | Thiazide or Thiazide-like diuretics Wiki | 0.06 |
drug877 | Umbilical cord Wharton's jelly-derived human Wiki | 0.06 |
drug444 | Isotonic saline 0.9% Wiki | 0.06 |
drug530 | NK Cells Wiki | 0.06 |
drug79 | Awake Proning Wiki | 0.06 |
drug599 | Pathogen-specific aAPC Wiki | 0.06 |
drug603 | Peginterferon Lambda-1A Wiki | 0.06 |
drug965 | hyperbaric oxygen therapy (HBOT) Wiki | 0.06 |
drug734 | Satisfaction evaluation Wiki | 0.06 |
drug284 | Enoxaparin Wiki | 0.06 |
drug930 | bidirectional oxygenation mouthpiece Wiki | 0.06 |
drug839 | The standard Macintosh laryngoscope Wiki | 0.06 |
drug140 | Burnout Wiki | 0.06 |
drug475 | Lopinavir and Ritonavir Tablets Wiki | 0.06 |
drug61 | Ascorbic Acid and Folic Acid Wiki | 0.06 |
drug876 | Umbilical Cord Mesenchymal Stem Cells Wiki | 0.06 |
drug380 | Hydroxychloroquine Sulfate 200 MG [Plaquenil] Wiki | 0.06 |
drug797 | Study C Wiki | 0.06 |
drug621 | Placebo Vaccine Wiki | 0.06 |
drug655 | Prone position Wiki | 0.06 |
drug519 | MultiStem Wiki | 0.06 |
drug910 | XPro1595 Wiki | 0.06 |
drug1002 | pirfenidone Wiki | 0.06 |
drug374 | Hydroxychloroquine SAR321068 Wiki | 0.06 |
drug882 | Use of social media during COVID-19 Wiki | 0.06 |
drug1034 | this study is non- interventional Wiki | 0.06 |
drug978 | meplazumab for injection Wiki | 0.06 |
drug477 | Lopinavir/Ritonavir Wiki | 0.06 |
drug728 | Saline with Baby Shampoo Nasal Irrigation Wiki | 0.06 |
drug505 | Mesenchymal cells Wiki | 0.06 |
drug50 | Angiotensin receptor blocker Wiki | 0.06 |
drug1029 | standard treatment Wiki | 0.06 |
drug1013 | rapid salivary test Wiki | 0.06 |
drug315 | Fondaparinux Wiki | 0.06 |
drug915 | Zinc Wiki | 0.06 |
drug942 | cholecalciferol 50,000 IU Wiki | 0.06 |
drug569 | Nutrition support Wiki | 0.06 |
drug608 | Peripheral blood draw Wiki | 0.06 |
drug646 | Practice details Wiki | 0.06 |
drug154 | COVID-19 convalescent plasma Wiki | 0.06 |
drug373 | Hydroxychloroquine Pre-Exposure Prophylaxis Wiki | 0.06 |
drug218 | Continuation of ARB/ACEI Wiki | 0.06 |
drug227 | Convalescent Plasma Transfusion Wiki | 0.06 |
drug956 | high flow nasal cannula (HFNC) Wiki | 0.06 |
drug1038 | turkish physicians Wiki | 0.06 |
drug427 | Insulin regimen Wiki | 0.06 |
drug742 | Serology Wiki | 0.06 |
drug563 | Non-Interventional Wiki | 0.06 |
drug916 | Zinc Gluconate Wiki | 0.06 |
drug191 | Chloroquine Diphosphate Wiki | 0.06 |
drug859 | Tradipitant Wiki | 0.06 |
drug472 | Lopinavir / ritonavir tablets combined with Xiyanping injection Wiki | 0.06 |
drug431 | Interferon-Beta Wiki | 0.06 |
drug952 | exercise brochure Wiki | 0.06 |
drug251 | Data record Wiki | 0.06 |
drug938 | care modalities Wiki | 0.06 |
drug123 | Biomarkers expression Wiki | 0.06 |
drug660 | Psychological and physical rehabilitation based humanistic care Wiki | 0.06 |
drug80 | Ayurveda Wiki | 0.06 |
drug56 | Any drug used to treat Covid-19 Wiki | 0.06 |
drug665 | Q-NRG Metobolic Cart Device Wiki | 0.06 |
drug508 | Methylprednisolone Sodium Succinate Wiki | 0.06 |
drug358 | Hydoxychloroquine or Chloroquine Wiki | 0.06 |
drug581 | Oral placebo Wiki | 0.06 |
drug449 | Ivermectine Wiki | 0.06 |
drug90 | BAT + Calcifediol Wiki | 0.06 |
drug416 | Impact Event Score Wiki | 0.06 |
drug415 | Immunological profiling Wiki | 0.06 |
drug443 | Isoprinosine Wiki | 0.06 |
drug215 | Comprehensive treatment Wiki | 0.06 |
drug982 | monthly serologic IgM/G test Wiki | 0.06 |
drug989 | no intervention Wiki | 0.06 |
drug575 | Odd/Even birth year intervention groups Wiki | 0.06 |
drug436 | Internet-delivered cognitive behavior therapy (ICBT) for dysfunctional worry related to the Covid-19 pandemic Wiki | 0.06 |
drug70 | Association of diltiazem and niclosamide Wiki | 0.06 |
drug52 | Anti- SARS-CoV-2 Plasma Wiki | 0.06 |
drug868 | Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule Wiki | 0.06 |
drug780 | Standard screening strategy Wiki | 0.06 |
drug677 | Radiological Detection Wiki | 0.06 |
drug199 | Clazakizumab Wiki | 0.06 |
drug54 | Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients Wiki | 0.06 |
drug327 | Group B Control Wiki | 0.06 |
drug567 | Normal saline Wiki | 0.06 |
drug614 | Piclidenoson Wiki | 0.06 |
drug125 | Biosensors Wiki | 0.06 |
drug485 | MRx-4DP0004 Wiki | 0.06 |
drug601 | Patient sampling Wiki | 0.06 |
drug809 | Systemic indirect endovenous ozone therapy Wiki | 0.06 |
drug506 | Messaging Wiki | 0.06 |
drug409 | IV Deployment Of cSVF In Sterile Normal Saline IV Solution Wiki | 0.06 |
drug84 | Azithromycin 500 mg Wiki | 0.06 |
drug897 | Video-Based Wiki | 0.06 |
drug390 | Hydroxychloroquine and azithromycin treatment Wiki | 0.06 |
drug1026 | standard operating procedures Wiki | 0.06 |
drug308 | Fingolimod 0.5 mg Wiki | 0.06 |
drug715 | SARS-CoV-2 IgG Antibody Testing Kit Wiki | 0.06 |
drug573 | Observational Study Wiki | 0.06 |
drug969 | intradermal injection of BCG Vaccine Wiki | 0.06 |
drug926 | artus Influenza A/B RT-PCR Test Wiki | 0.06 |
drug424 | Inhaled nitric oxide gas Wiki | 0.06 |
drug955 | global survey Wiki | 0.06 |
drug928 | bacTRL-Spike Wiki | 0.06 |
drug939 | chlorine dioxide 3000 ppm Wiki | 0.06 |
drug412 | Imatinib Wiki | 0.06 |
drug78 | Aviptadil by intravenous infusion + maximal intensive care Wiki | 0.06 |
drug572 | Observational (registry) Wiki | 0.06 |
drug1011 | questionnair about Emerging Legal and Ehical Disputes Over Patient Confidentiality Wiki | 0.06 |
drug31 | Acetylsalicylic acid Wiki | 0.06 |
drug1004 | placebo for clazakizumab Wiki | 0.06 |
drug341 | Health Care Worker Survey Wiki | 0.06 |
drug165 | CT-imaging Wiki | 0.06 |
drug410 | Ibuprofen Wiki | 0.06 |
drug994 | observation Wiki | 0.06 |
drug153 | COVID-19 barrier box Wiki | 0.06 |
drug896 | Video based exercise Wiki | 0.06 |
drug940 | chloroquine Wiki | 0.06 |
drug941 | cholecalciferol 200,000 IU Wiki | 0.06 |
drug985 | muscle ultrasound Wiki | 0.06 |
drug822 | Teleconsultation either by phone or by computer consultation Wiki | 0.06 |
drug830 | Telmisartan arm will receive 80 mg Telmisartan twice daily plus standard care. Wiki | 0.06 |
drug541 | Natural Honey Wiki | 0.06 |
drug657 | Prone positioning (PP) Wiki | 0.06 |
drug463 | Liberase Enzyme (Roche) Wiki | 0.06 |
drug999 | oxygen treatment Wiki | 0.06 |
drug861 | Transfusion of COVID-19 convalescent plasma Wiki | 0.06 |
drug971 | laboratory biomarkers Wiki | 0.06 |
drug1000 | oxyhydrogen Wiki | 0.06 |
drug626 | Placebo oral capsule Wiki | 0.06 |
drug301 | Extra blood sample Wiki | 0.06 |
drug239 | Cytokine Adsorption Wiki | 0.06 |
drug716 | SARS-CoV-2 non-immune Plasma Wiki | 0.06 |
drug578 | Online Survey Wiki | 0.06 |
drug442 | Intravenous saline injection (Placebo) Wiki | 0.06 |
drug168 | Cambridge Validated Viral Detection Method Wiki | 0.06 |
drug988 | newborns from covid 19 positive mothers Wiki | 0.06 |
drug483 | Low-dose chloroquine/hydroxychloroquine Wiki | 0.06 |
drug947 | convalescent plasma from recovered COVID 19 donor Wiki | 0.06 |
drug922 | allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC) Wiki | 0.06 |
drug451 | Kerecis Oral and Nasal Spray Wiki | 0.06 |
drug377 | Hydroxychloroquine Sulfate + Azithromycin Wiki | 0.06 |
drug481 | Low Dose Radiation Therapy Wiki | 0.06 |
drug932 | blood donation SMS Wiki | 0.06 |
drug514 | Monitoring Visit - Baseline Wiki | 0.06 |
drug297 | Experimental: Questionnaire without precaution information Wiki | 0.06 |
drug885 | Usual care Wiki | 0.06 |
drug495 | Matrix-M Adjuvant Wiki | 0.06 |
drug959 | hospitalized children with Covid19 Wiki | 0.06 |
drug305 | Favipiravir + Standard of Care Wiki | 0.06 |
drug804 | Survey and Questionnaire Wiki | 0.06 |
drug27 | AZ Wiki | 0.06 |
drug488 | MVA-MERS-S_DF1 - High Dose Wiki | 0.06 |
drug426 | Injective placebo Wiki | 0.06 |
drug306 | Favipiravir tablets Wiki | 0.06 |
drug64 | Aspirin 100mg Wiki | 0.06 |
drug329 | HB-adMSC Wiki | 0.06 |
drug852 | To assess for development of IgG antibodies against SARS-CoV2 Wiki | 0.06 |
drug122 | Biological: COVID-19 convalescent plasma Wiki | 0.06 |
drug902 | Vitamins Wiki | 0.06 |
drug950 | daily syndromic surveillance Wiki | 0.06 |
drug471 | Lopinavir / Ritonavir plus Ribavirin Wiki | 0.06 |
drug252 | Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days Wiki | 0.06 |
drug515 | Monitoring Visit - Week 4 Wiki | 0.06 |
drug353 | Human Biological samples Wiki | 0.06 |
drug322 | General health education Wiki | 0.06 |
drug274 | EUROIMMUN assay Wiki | 0.06 |
drug588 | Oxygen-ozone therapy, probiotic supplementation and Standard of care Wiki | 0.06 |
drug571 | Observation of patients with known, suspected, or at risk for COVID-19 infection Wiki | 0.06 |
drug798 | Study Group Wiki | 0.06 |
drug643 | Povidone-Iodine 2% Wiki | 0.06 |
drug869 | Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule Wiki | 0.06 |
drug843 | Thoracic CT Scan Wiki | 0.06 |
drug751 | Sirolimus 1 MG/ML Wiki | 0.06 |
drug777 | Standard of care therapy Wiki | 0.06 |
drug829 | Telmisartan 40mg Wiki | 0.06 |
drug36 | Alferon LDO Wiki | 0.06 |
drug24 | ASC09/ritonavir group Wiki | 0.06 |
drug278 | Electric pad for human external pain therapy Wiki | 0.06 |
drug331 | HC Wiki | 0.06 |
drug767 | Standard Public Health measures Wiki | 0.06 |
drug44 | Amiodarone Wiki | 0.06 |
drug683 | Recombinant Human Interferon α2b Spray Wiki | 0.06 |
drug795 | Study A Wiki | 0.06 |
drug911 | Xiyanping injection Wiki | 0.06 |
drug639 | Postpartum women under investigation for Coronavirus or diagnosed with COVID-19 Wiki | 0.06 |
drug95 | BLD-2660 Wiki | 0.06 |
drug368 | Hydroxychloroquine - Daily Dosing Wiki | 0.06 |
drug41 | Alteplase 50 MG [Activase] Wiki | 0.06 |
drug103 | BVRS-GamVac Wiki | 0.06 |
drug687 | Recombinant human interferon α1β Wiki | 0.06 |
drug388 | Hydroxychloroquine Sulfate and Folic Acid Wiki | 0.06 |
drug870 | Two doses of placebo at the emergency vaccination schedule Wiki | 0.06 |
drug186 | ChAdOx1 nCoV-19 boost Wiki | 0.06 |
drug698 | Ribavirin Wiki | 0.06 |
drug352 | Huaier Granule Wiki | 0.06 |
drug51 | Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) Wiki | 0.06 |
drug726 | Saline Nasal Irrigation Wiki | 0.06 |
drug631 | Placebo: Hydroxychloroquine Wiki | 0.06 |
drug879 | Unfractionated heparin Wiki | 0.06 |
drug676 | REGN3051 Wiki | 0.06 |
drug212 | Combination of Lopinavir /Ritonavir and Interferon beta-1b Wiki | 0.06 |
drug811 | T89 Wiki | 0.06 |
drug11 | 2019-nCoV PCR Wiki | 0.06 |
drug338 | HOME-CoV rule implementation Wiki | 0.06 |
drug921 | all treatment about COVID-2019 Wiki | 0.06 |
drug740 | Sequencing Wiki | 0.06 |
drug974 | lopinavir/ritonavir tablets or Arbidol or chloroquine phosphate Wiki | 0.06 |
drug670 | Questionnaire with precaution information Wiki | 0.06 |
drug849 | Thymosin+standard treatment Wiki | 0.06 |
drug653 | Prone Wiki | 0.06 |
drug1005 | plasma therapy using convalescent plasma with antibody against SARS-CoV-2 Wiki | 0.06 |
drug733 | Sarilumab SAR153191 Wiki | 0.06 |
drug749 | Simvastatin Wiki | 0.06 |
drug675 | REGN3048 Wiki | 0.06 |
drug147 | COPAN swabbing and blood sample collection Wiki | 0.06 |
drug185 | ChAdOx1 nCoV-19 Wiki | 0.06 |
drug744 | Serum test Wiki | 0.06 |
drug737 | Self-prone position recommendation Wiki | 0.06 |
drug619 | Placebo 250 cc 24 hours continuous infusion for 15 days Wiki | 0.06 |
drug1014 | recombinant human interferon Alpha-1b Wiki | 0.06 |
drug49 | Angiotensin 1-7 Wiki | 0.06 |
drug741 | Serological test Wiki | 0.06 |
drug489 | MVA-MERS-S_DF1 - Low Dose Wiki | 0.06 |
drug350 | Honey Wiki | 0.06 |
drug432 | Interferon-β 1a Wiki | 0.06 |
drug970 | isocaloric/isonutrigenous ONS Wiki | 0.06 |
drug637 | Point-of-Care Ultrasonography (POCUS) Wiki | 0.06 |
drug606 | Pegylated interferon lambda Wiki | 0.06 |
drug919 | a specifically designed self-administered questionnaire Wiki | 0.06 |
drug74 | Auto-questionnaires (patients co infected HIV Sras-CoV-2) Wiki | 0.06 |
drug67 | Assessment of Dietary Changes in Adults in the Quarantine Wiki | 0.06 |
drug535 | NaCl 0.9% Wiki | 0.06 |
drug487 | MSCs-derived exosomes Wiki | 0.06 |
drug112 | Best Available Therapy Wiki | 0.06 |
drug641 | Povidone-Iodine Wiki | 0.06 |
drug312 | Fluvoxamine Wiki | 0.06 |
drug1028 | standard therapy Wiki | 0.06 |
drug418 | Individualised Ayurveda Wiki | 0.06 |
drug580 | Oral Wiki | 0.06 |
drug825 | Telephone survey Wiki | 0.06 |
drug177 | Carrimycin Wiki | 0.06 |
drug686 | Recombinant human angiotensin-converting enzyme 2 (rhACE2) Wiki | 0.06 |
drug104 | BVRS-GamVac-Combi Wiki | 0.06 |
drug642 | Povidone-Iodine 0.5% Wiki | 0.06 |
drug512 | Mindfulness-based "STOP touching your face" practice Wiki | 0.06 |
drug645 | Powered Air purifying respirator Wiki | 0.06 |
drug724 | STC-19 score Wiki | 0.06 |
drug953 | favipiravir Wiki | 0.06 |
drug564 | Non-convalescent Plasma (control plasma) Wiki | 0.06 |
drug1006 | prayer Wiki | 0.06 |
drug42 | Aluminum hydroxide Wiki | 0.06 |
drug96 | BM-MSCs Wiki | 0.06 |
drug1021 | serum inflammatory biomarkers Wiki | 0.06 |
drug628 | Placebo plus standard preventive measures Wiki | 0.06 |
drug59 | Arbidol Hydrochloride Granules Wiki | 0.06 |
drug334 | HCQ + Intravenous Famotidine Wiki | 0.06 |
drug229 | Convalescent anti-SARS-CoV-2 plasma Wiki | 0.06 |
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Name (Synonyms) | Correlation | |
---|---|---|
D045169 | Severe Acute Respiratory Syndrome NIH | 0.79 |
D014777 | Virus Diseases NIH | 0.35 |
D003141 | Communicable Diseases NIH | 0.29 |
D007239 | Infection NIH | 0.29 |
D013577 | Syndrome NIH | 0.22 |
D011014 | Pneumonia NIH | 0.20 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.16 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.15 |
D055371 | Acute Lung Injury NIH | 0.14 |
D011024 | Pneumonia, Viral NIH | 0.13 |
D003333 | Coronaviridae Infections NIH | 0.10 |
D058070 | Asymptomatic Diseases NIH | 0.08 |
D012327 | RNA Virus Infections NIH | 0.08 |
D013313 | Stress Disorders, Post-Traumatic NIH | 0.08 |
D012141 | Respiratory Tract Infections NIH | 0.07 |
D003924 | Diabetes Mellitus, Type 2 NIH | 0.06 |
D003920 | Diabetes Mellitus, NIH | 0.06 |
D016638 | Critical Illness NIH | 0.06 |
D006470 | Hemorrhage NIH | 0.06 |
D008659 | Metabolic Diseases NIH | 0.06 |
D003384 | Coxsackievirus Infections NIH | 0.06 |
D006929 | Hyperaldosteronism NIH | 0.06 |
D003428 | Cross Infection NIH | 0.06 |
D014552 | Urinary Tract Infections NIH | 0.06 |
D004700 | Endocrine System Diseases NIH | 0.06 |
D054990 | Idiopathic Pulmonary Fibrosis NIH | 0.06 |
D000309 | Adrenal Insufficiency NIH | 0.06 |
D012772 | Shock, Septic NIH | 0.06 |
D054559 | Hyperphosphatemia NIH | 0.06 |
D007154 | Immune System Diseases NIH | 0.06 |
D011649 | Pulmonary Alveolar Proteinosis NIH | 0.06 |
D007008 | Hypokalemia NIH | 0.06 |
D019446 | Endotoxemia NIH | 0.06 |
D019851 | Thrombophilia NIH | 0.06 |
D040921 | Stress Disorders, Traumatic NIH | 0.06 |
D016769 | Embolism and Thrombosis NIH | 0.06 |
D018805 | Sepsis NIH | 0.06 |
D004617 | Embolism NIH | 0.06 |
D000208 | Acute Disease NIH | 0.06 |
D008171 | Lung Diseases, NIH | 0.06 |
D001997 | Bronchopulmonary Dysplasia NIH | 0.06 |
D011565 | Psoriasis NIH | 0.06 |
D055501 | Macrophage Activation Syndrome NIH | 0.06 |
D009220 | Myositis NIH | 0.06 |
D007049 | Iatrogenic Disease NIH | 0.06 |
D044882 | Glucose Metabolism Disorders NIH | 0.06 |
D008595 | Menorrhagia NIH | 0.06 |
D009205 | Myocarditis NIH | 0.06 |
D006973 | Hypertension NIH | 0.05 |
D058186 | Acute Kidney Injury NIH | 0.05 |
D003863 | Depression, NIH | 0.05 |
D012140 | Respiratory Tract Diseases NIH | 0.04 |
D009369 | Neoplasms, NIH | 0.04 |
D007251 | Influenza, Human NIH | 0.04 |
D030341 | Nidovirales Infections NIH | 0.04 |
D003139 | Common Cold NIH | 0.04 |
D003289 | Convalescence NIH | 0.04 |
D000257 | Adenoviridae Infections NIH | 0.04 |
D000860 | Hypoxia NIH | 0.04 |
D019337 | Hematologic Neoplasms NIH | 0.03 |
D011658 | Pulmonary Fibrosis NIH | 0.03 |
D011665 | Pulmonary Valve Insufficiency NIH | 0.03 |
D029424 | Pulmonary Disease, Chronic Obstructive NIH | 0.03 |
D004417 | Dyspnea NIH | 0.03 |
D018184 | Paramyxoviridae Infections NIH | 0.03 |
D017563 | Lung Diseases, Interstitial NIH | 0.03 |
D001008 | Anxiety Disorders NIH | 0.03 |
D012769 | Shock, NIH | 0.03 |
D018357 | Respiratory Syncytial Virus Infections NIH | 0.03 |
D008173 | Lung Diseases, Obstructive NIH | 0.03 |
D007249 | Inflammation NIH | 0.03 |
D013927 | Thrombosis NIH | 0.02 |
D018450 | Disease Progression NIH | 0.02 |
D053717 | Pneumonia, Ventilator-Associated NIH | 0.02 |
D004630 | Emergencies NIH | 0.02 |
D055370 | Lung Injury NIH | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0002090 | Pneumonia HPO | 0.13 |
HP:0000132 | Menorrhagia HPO | 0.06 |
HP:0002665 | Lymphoma HPO | 0.06 |
HP:0002900 | Hypokalemia HPO | 0.06 |
HP:0000859 | Hyperaldosteronism HPO | 0.06 |
HP:0010444 | Pulmonary insufficiency HPO | 0.06 |
HP:0000846 | Adrenal insufficiency HPO | 0.06 |
HP:0002791 | Hypoventilation HPO | 0.06 |
HP:0000822 | Hypertension HPO | 0.04 |
HP:0002098 | Respiratory distress HPO | 0.04 |
There are 318 clinical trials
Triple 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 startSevere 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 purpose of this study is to understand how severe acute respiratory syndrome (SARS) spreads within families, if significant disease resulted, and how the body responds to SARS. The study will also explore the affects of SARS on genetics and the immune system (the body system that fights disease). Up to 1000 people residing in Beijing, China may be involved in this study. Adult survivors of SARS (numbering 200) and their family members including children age 4 and up will be asked to participate in the study. The study will recruit an additional 200 persons, who will be matched with SARs survivors of similar age, gender, health status, and housing/work location, and recruited as comparators. Blood will be taken from all volunteers and tested for the presence of SARS antibodies (proteins made by the body's immune system in response to something that can cause infection). Health and clinic/hospital visit records may be reviewed.
Severe acute respiratory syndrome (SARS) is a viral illness that affects the respiratory (breathing) system. The purpose of this study is to evaluate the safety and protective (immune) responses to different doses of a SARS vaccine given with or without an adjuvant. An adjuvant is a substance that may be added to a vaccine to improve the immune response so that less of the vaccine may need to be given. Study participants will include 72 volunteers, ages 18-40, living in the Houston, Texas area. The study will take place at Baylor College of Medicine. Participants will receive 2 injections of vaccine or placebo (substance made to look like the study vaccine but contains no medication) given 1 month apart. Participants will fill out a memory aid (diary) to document daily temperature and illness signs and symptoms for 7-9 days after each injection. During the 9 study visits, several blood samples will be collected. Participants will be in the study for up to 211 days, including screening.
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 study will be conducted using nasopharyngeal swab specimens collected prospectively from individuals suspected of having the signs and symptoms of an acute respiratory tract infection caused by a respiratory virus. A series of standard viral culture tests validated for routine use in the clinical laboratory, and/or a series of PCR-based Laboratory Developed Tests (PCR-LDT) validated by a central reference laboratory will be used to verify the performance of the investigational artus Influenza A/B RT-PCR test and the QIAGEN ResPlex II Advanced Panel test. From each specimen five (5) aliquots will be prepared: (a) one aliquot will be tested in real-time using the assigned viral culture reference methods; (b) one aliquot will be used to extract nucleic acid in real-time for investigational testing; (c) one aliquot of the specimen will be stored at --70C for subsequent shipment to the reference laboratory for PCR-LDT testing, (d) one aliquot will be archived at -70C for subsequent follow-up by the reference laboratory (e.g., bi-directional sequencing of positive specimens), and (e) any remaining specimen will be stored for the Fresh vs. Frozen Study. The extracted nucleic acid generated from the second aliquot (i.e., "b" above) will be split and subjected to testing by both the artus Influenza A/B RT-PCR test and the ResPlex II Advanced Panel test.
Description: The presence of Influenza A or Influenza B virus.
Measure: Detection of Respiratory Viruses Time: Specimens will be taken within 5 days of the appearance of symptoms.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 monthBackground: Middle East Respiratory Syndrome (MERS) is a newly discovered contagious and sometimes fatal respiratory virus. People often get MERS through close contact with an infected person. Scientists are worried that MERS may spread and cause more infections. There are no vaccines or treatments for MERS right now. Researchers think a new therapy called SAB-301 may be able to help. Antibodies are proteins the body makes to attack viruses. SAB-301 is made of antibodies made in cows to fight MERS. The antibodies are collected from plasma, the liquid part of cow blood. Objective: To evaluate the safety and tolerability of SAB-301 in healthy adults. Eligibility: Healthy people ages 18 60 who: Do not have chronic medical problems Do not take any medications (exceptions are acetaminophen, ibuprofen, vitamins, seasonal allergy meds and oral contraception) Do not have allergies to beef products Agree to use two forms of contraception while on study (both men and women) Design: Participants will be screened with: Medical history Physical examination Blood and urine tests Participants will have a return visit. They will have a physical exam and blood tests. They will be randomly assigned to receive either SAB-301 or a placebo which is given by infusion through an arm vein over 1 3 hours. They will be monitored at the clinic for 6 hours after the infusion. They will have additional blood draws. Participants will have 2-hour visits 1, 3, 7, 21, 42, and 90 days after the infusion. At each visit they will be evaluated and have blood and urine tests.
Description: Number of participants who experienced an adverse event
Measure: Number of Participants Having Adverse Events Time: 90 daysThis is a placebo-controlled clinical trial to assess the feasibility, efficacy and safety of a combination of lopinavir/ritonavir and Interferon beta-1b in hospitalized patients with MERS.
Description: Infections will be reported as per the NHSN 2016 definitions, as number of events per devise day or ICU day as appropriate.
Measure: Hospital-acquired infections as assessed by the NHSN 2016 definitions Time: Up to one year from enrollmentThis 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 26This is a clinical trial in which healthy volunteers will be administered an experimental MERS vaccine. The vaccine ChAdOx1 MERS will be administered alone both as a single administration and with a homologous prime-booster.
Description: The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. Change from baseline for safety laboratory measures will also be collected. Occurrence of serious adverse events will be collected during the whole study duration
Measure: Occurrence of solicited and unsolicited local and systemic adverse events Time: up to 28 days following vaccinationDescription: ELISA to quantify antibodies to MERS Spike protein antigen Ex vivo ELISpot responses to MERS Spike protein antigen
Measure: Measures of immunogenicity to the ChAdOx1 MERS vaccine Time: 12 monthsSARS-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 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a potentially fatal disease with a reported lethality of up to 40% that is under tight epidemiologic control by the World Health Organization (WHO) and currently without registered prevention or treatment option. In this phase I first-in-human clinical trial, healthy volunteers in two different dose cohorts will be vaccinated twice with the candidate vaccine MVA-MERS-S. A subgroup will additionally receive a late booster vaccination. The aim of the study is to assess the safety and tolerability of the candidate vaccine and to characterize its immunogenicity.
Description: The solicited local adverse events for this study include: Swelling, erythema, induration, hematoma and pain at site of injection The solicited systemic adverse events for this study include: Fever Chills Myalgia (described to the subject as generalized muscle aches) Arthralgia (described to the subject as generalized joint aches) Fatigue/Malaise Headache Gastrointestinal symptoms The reactogenicity (adverse events) will be assessed via a trained physician taking into account a patient diary. The severity of the adverse event will be measured as specified in the study protocol (grade 0=none, grade 1=mild, grade 2=moderate, grade 3=severe). The adverse event will furthermore be categorized in related vs. not related.
Measure: Occurrence of solicited local and systemic reactogenicity as defined by the study protocol Time: 14 days after each vaccinationDescription: The unsolicited adverse events will be assessed via a trained physician taking into account a patient diary. The severity of the adverse event will be measured as specified in the study protocol (grade 0=none, grade 1=mild, grade 2=moderate, grade 3=severe). The adverse event will furthermore be categorized in related vs. not related.
Measure: Occurrence of unsolicited adverse events Time: 28 days after each vaccinationDescription: The safety laboratory measures include: Troponin T Clinical Chemistry Hematology Urine
Measure: Change from baseline of safety laboratory measures as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 Time: Throughout the study up to conclusionDescription: Serious adverse events are defined as any untoward medical occurrence (whether considered to be related to investigational medicinal product or not) that at any dose: results in death is life-threatening requires inpatient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity is a congenital abnormality/birth defect is an Important Medical Event, i.e., an event that may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Measure: Occurrence of serious adverse events Time: Throughout the study up to conclusionDescription: Humoral immunity: The magnitude of MVA-MERS-S antibody responses as assessed by neutralization assay and ELISA
Measure: Measures of immunogenicity to the MVA-MERS-S vaccine Time: Throughout the study up to conclusionThe primary objective of this study is to evaluate the safety and tolerability of TAK-981 as a single agent in participants with advanced or metastatic solid tumors and lymphomas in dose escalation and cancer treatment expansions, and to assess change in acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load within 8 days of TAK-981 administration in COVID expansion.
Description: CRS will be graded as per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS.
Measure: Dose Escalation and Cancer Treatment Expansions: Number of Participants who Experience Cytokine Release Syndrome CRS) Time: Up to 36 monthsDescription: ORR is defined as percentage of participants who achieve complete response (CR) and partial response (PR) through the study (approximately 3 years), as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1) for participants with solid tumors and Response Evaluation Criteria in Lymphoma (RECIL) for participants with lymphoma.
Measure: Dose Escalation and Cancer Treatment Expansions: Overall Response Rate (ORR) Time: From the first dose until best response is achieved (up to approximately 3 years)Description: DOR will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.
Measure: Dose Escalation and Cancer Treatment Expansions: Duration of Response (DOR) Time: From the time of documentation of tumor response to the first recorded occurrence of disease progression (PD) or death from any cause (whichever occurs first), through end of study (up to approximately 3 years)Description: DCR is defined as percentage of participants who achieve stable disease (SD) or better greater than (>) 6 weeks during the study in response-evaluable population, as determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.
Measure: Dose Escalation and Cancer Treatment Expansions: Disease Control Rate (DCR) Time: From the first dose until best response is achieved (up to approximately 3 years)Description: PFS will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.
Measure: Dose Escalation and Cancer Treatment Expansions: Progression-free Survival (PFS) Time: From the date of the first dose administration to the date of first documentation of PD or death due to any cause whichever occurs first, through the end of the study (up to approximately 3 years)Description: TTR will be determined by the investigator according to RECIST V1.1 for participants with solid tumors and RECIL for participants with lymphoma.
Measure: Dose Escalation and Cancer Treatment Expansions: Time to Response (TTR) Time: From the date of first study drug administration to the date of first documented PR or better (up to approximately 3 years)Description: Severity Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 5.0.
Measure: COVID-19 Expansion: Number of Participants Based on Severity of TEAEs Time: Up to 9 monthsDescription: CRS will be graded as per ASTCT Consensus Grading for CRS.
Measure: COVID-19 Expansion: Number of Participants who Experience CRS Time: Up to 9 monthsDescription: NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.
Measure: COVID-19 Expansion: Change from Baseline in National Early Warning Score (NEWS) Time: Up to 9 monthsDescription: Percentage of participants will be reported based on severity rating on a 6-point ordinal scale, which will include: 1 (death); 2 (hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation, hospitalized); 3 (on non-invasive ventilation or high flow oxygen devices); 4 (hospitalized, requiring supplemental oxygen); 5 (hospitalized, not requiring supplemental oxygen); and 6 (not hospitalized).
Measure: COVID-19 Expansion: Percentage of Participants Reporting Each Hospitalization Severity Rating Time: Up to 9 monthsDescription: Change from Baseline in SARS-CoV-2 viral Load in nasopharyngeal or oropharyngeal samples will be determined by viral response. The nasopharyngeal swab will be collected from both nostrils or from the same nostril every time.
Measure: COVID-19 Expansion: Change From Baseline in SARS-CoV-2 Viral Load in Nasopharyngeal or Oropharyngeal Samples Time: Up to 9 monthsDescription: Time from the first dose of TAK-981 to viral load negativity (below level of detection).
Measure: COVID-19 Expansion: Time to Viral Ribonucleic Acid (RNA) Negativity in Nasopharyngeal or Oropharyngeal Samples Time: Up to 9 monthsDescription: Time from first dose of TAK-981 to participant's discharge or to NEWS score <=3. NEWS determines the degree of illness of participants and prompts critical care intervention. It will be based on the score allocated to respiratory rate, peripheral capillary oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate and level of consciousness.
Measure: COVID-19 Expansion: Time to Discharge or to a NEWS of Less Than or Equal to (<=) 3 and Maintained for 24 Hours Time: Up to 9 monthsLOVIT is a multicentre concealed-allocation parallel-group blinded randomized controlled trial to ascertain the effect of high-dose intravenous vitamin C compared to placebo on mortality or persistent organ dysfunction at 28 days in septic intensive care unit patients. Patients with COVID-19 are considered eligible for this study.
Description: Defined as death or dependency on mechanical ventilation, renal replacement, or vasopressors
Measure: Number of deceased participants or with persistent organ dysfunction Time: Both assessed at 28 daysDescription: Persistent organ dysfunction-free days in intensive care unit
Measure: Number of participants with persistent organ dysfunction-free days in intensive care unit Time: Up to day 28Description: Mortality at 6 months
Measure: Number of participants deceased at 6 months Time: 6 monthsDescription: Assessed by the questionnaire EuroQol-5D (EQ-5D-5L). The EQ-5D-5L essentially consists of 2 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. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'.
Measure: Score of health related quality of life in 6-month survivors Time: 6 monthsDescription: Assessed by serum lactate concentration
Measure: Global tissue dysoxia Time: Days 1, 3, 7Description: Assessed by the Sequential Organ Failure Assessment (SOFA) score. Used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on 6 different sub-scores, one each for the respiratory (PaO2/FiO2 mmHg), cardiovascular (mean arterial pressure OR administration of vasopressors required), hepatic (liver bilirubin (mg/dl) [μmol/L]), coagulation (platelets×103/µl), renal (kidneys creatinine (mg/dl) [μmol/L] (or urine output)) and neurological (Glasgow coma scale). The sub-score of eah system ranges from 0 (best) to +4 (worst).
Measure: Organ function (including renal function) Time: Days 1, 2, 3, 4, 7, 10, 14, 28Description: Assessed by interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP)
Measure: Rate of inflammation Time: Days 1, 3, 7Description: Assessed by procalcitonin (PCT)
Measure: Rate of infection Time: Days 1, 3, 7Description: Assessed by thrombomodulin (TM) and angiopoietin-2 (ANG-2)
Measure: Rate of endothelial injury Time: Days 1, 3, 7Description: Assessed by KDIGO (Kidney Disease: Improving Global Outcomes) criteria
Measure: Occurrence of stage 3 acute kidney injury Time: Up to day 28Description: clinician judgment of hemolysis, as recorded in the chart, OR hemoglobin drop of at least 25 g/L within 24 hours of a dose of investigational product PLUS 2 of the following: reticulocyte count >2 times upper limit of normal at clinical site lab; haptoglobin < lower limit of normal at clinical site lab; indirect (unconjugated) bilirubin >2 times upper limit of normal at clinical site lab; Lactate dehydrogenase (LDH) >2 times upper limit of normal at clinical site lab. Severe hemolysis: - hemoglobin < 75 g/L AND at least 2 of the above criteria AND requires 2 units of packed red blood cells
Measure: Acute hemolysis Time: Up to day 28Description: Core lab-validated glucose level of less than 3.8 mmol/L
Measure: Hypoglycemia Time: During the time participants receive the 16 doses of the investigational product and the 7 days following the last doseDescription: Assessed by chromatography-tandem mass spectrometry
Measure: Vitamin C volume of distribution Time: 6th dose of vitamin C (second dose on day 2) at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy)Description: Assessed by chromatography-tandem mass spectrometry
Measure: Vitamin C clearance Time: 6th dose of vitamin C (second dose on day 2) at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy)Description: Assessed by chromatography-tandem mass spectrometry
Measure: Vitamin C plasma concentration Time: 6th dose of vitamin C (second dose on day 2) at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy)The study will be a two center, randomized, double blind, placebo controlled study of the MVA MERS S_DF-1 candidate delivered by i.m. injection. To evaluate the MERS-S-specific antibody responses and safety profile induced by the two dosage levels of MVA-MERS-S_DF-1 the data will be compared to a placebo control group.
Description: Safety and reactogenicity will be assesssed by observation, questionaire and diary. Changes from baseline for safety laboratory measures will be monitored. Occurence of SAE will be collected throughout the entire study duration.
Measure: Frequency of adverse events associated with MVA-MERS-S_DF-1. Time: day 1, 14, 29, 42, 56, 84, 168, 336, 364Description: Magnitude of MERS-S-specific antibody re-sponses (ELISA and neutralization assays) monitored in a centralized approved laboratory
Measure: Immunogenicity Time: day 0, 14, 28, 42, 56, 70, 84, 168, 336, 364 (dependent on vaccination scheme)The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreak. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~34.5%. The aim of the study is to assess the safety and immunogenicity of heterologous adenoviral-based vaccine against MERS - BVRS-GamVac-Combi.
Description: Determination of Number of Participants With Adverse Events
Measure: Number of Participants With Adverse Events Time: through the whole study, an average of 180 daysDescription: Determination of Number of Participants With Serious Adverse Events
Measure: Number of Participants With Serious Adverse Events Time: through the whole study, an average of 180 daysDescription: Determination of Number of Participants with Solicited Local and Systemic Adverse Events
Measure: Number of Participants with Solicited Local and Systemic Adverse Events Time: through the whole study, an average of 180 daysDescription: Determination of antibody levels against the MERS-CoV glycoprotein S measured by an ELISA vs. baseline values (phase 1, phase 2) and placebo (phase 2)
Measure: Antibody levels against the MERS-CoV glycoprotein S measured by an enzyme-linked immunosorbent assay (ELISA) Time: Time Frame for group 1 phase 1: at days 0, 7, 14, 21, 28, 42, 56 and 90. Time Frame for group 2 phase 1 and phase 2: at days 0, 7, 14, 21, 28, 35, 42, 56 and 90Description: determination of specific T-cell- mediated response vs. baseline values and placebo
Measure: Assessment of antigen-specific cell-mediated immune response Time: at 0, 14 and 28 days from the start of vaccination compared to baseline values (phase 1, phase 2) and placebo (phase 2)Description: Determination of the neutralizing antibody titer for a virus in virus neutralization reaction vs. baseline values and placebo
Measure: Neutralizing antibody levels Time: at days 0, 14 and 28 from the start of vaccination compared to baseline valuesThe Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreak. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~34.5%. The aim of the study is to assess the safety and immunogenicity of adenoviral-based vaccine against MERS - BVRS-GamVac.
Description: Determination of Number of Participants With Adverse Events
Measure: Number of Participants With Adverse Events Time: through the whole study, an average of 180 daysDescription: Determination of Number of Participants With Serious Adverse Events
Measure: Number of Participants With Serious Adverse Events Time: through the whole study, an average of 180 daysDescription: Determination of Number of Participants with Solicited Local and Systemic Adverse Events
Measure: Number of Participants with Solicited Local and Systemic Adverse Events Time: through the whole study, an average of 180 daysDescription: Determination of antibody levels against the MERS-CoV glycoprotein S measured by an ELISA vs. baseline values (phase 1, phase 2) and placebo (phase 2)
Measure: Antibody levels against the MERS-CoV glycoprotein S measured by an enzyme-linked immunosorbent assay (ELISA) Time: at days 0, 7, 14, 21, 28, 42, 56 and 90Description: determination of specific T-cell- mediated response vs. baseline values (phase 1, phase 2) and placebo (phase 2)
Measure: Assessment of antigen-specific cell-mediated immune response Time: at 0 and 14 days from the start of vaccination compared to baseline values (day 0)Description: Determination of the neutralizing antibody titer for a virus in virus neutralization reaction vs. baseline values
Measure: Neutralizing antibody levels Time: at days 0, 14 and 28A phase Ib study to determine the safety and immunogenicity of the candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) vaccine ChAdOx1 MERS in healthy adult Middle Eastern volunteers
Description: The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. Change from baseline for safety laboratory measures will also be collected. Occurrence of serious adverse events will be collected during the whole study duration
Measure: Occurrence of solicited and unsolicited local and systemic adverse events Time: 28 days following the vaccinationDescription: ELISA to quantify antibodies to MERS Spike protein antigen Ex vivo ELISpot responses to MERS Spike protein antigen
Measure: Measures of immunogenicity to the ChAdOx1 MERS vaccine Time: 6.5 months following completion of the vaccination regimenIn late December 2019, several local health facilities reported clusters of patients with pneumonia of unknown cause that were epidemiologically linked to a seafood and wet animal wholesale market in Wuhan, Hubei Province, China. It is now confirmed that the etiology of this outbreak is a novel coronavirus, namely, 2019-nCoV. Of critical importance is rapid and simple diagnostic method to be used in clinical settings to timely inform and refine strategies that can prevent, control, and stop the spread of 2019-nCoV. Recombinase aided amplification (RAA) assay is a novel isothermal nucleic acid amplification technique in recent years, which has a variety of the advantages including high specificity and sensitivity, rapid detection (30 min), low cost, low equipment requirements and simple operation. The has successfully detected a variety of pathogens using this technique. To develop a RAA assay for 2019-nCoV with the advantages of high speed, simple operation and low cost, and overcomes the shortcomings of the existing molecular detection methods. The investigators established a real time reverse-transcription RAA (RT-RAA) assay for detection of 2019-nCoV. This assay was performed at 42°C within 30min using a portable real-time fluorescence detector, Recombinant plasmids containing conserved ORF1ab genes was used to analyze the specificity and sensitivity. Clinical specimens from patients who were suspected of being infected with 2019-nCoV were used to evaluate the performance of the assay. In parallel, The investigators also used the commercial RT-qPCR assay kit for 2019-nCoV as a reference.
Description: Detection sensitivity is greater than 95%
Measure: Detection sensitivity is greater than 95% Time: at baselineDescription: Detection specificity is greater than 95%
Measure: Detection specificity is greater than 95% Time: at baselineDescription: Consistent with existing universal reagent detection rates greater than 95%
Measure: Consistent with existing universal reagent detection rates greater than 95% Time: at baselineThe 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 21In December 2019, a pneumonia due to a novel coronavirus (2019-nCoV) emerged in the city of Wuhan, in China. In a few weeks, the number of confirmed cases of 2019-nCoV infection has dramatically increased, with almost 20'000 cases and more than 400 reported deaths on January, 31st 2020. Little is known on the rate of human-to-human transmission of this new coronavirus 2019-nCoV. In France, subjects with contact considered to be at high or moderate risk of viral transmission with a laboratory-confirmed 2019-nCoV case are being isolated at their home for 14 days and followed up by Santé Publique France or the Agence Régionale de Santé. Whether such subjects become spreaders of the virus, nor is the proportion of viral spreader who will develop a symptomatic infection. In this study, the investigators aim to evaluate the virological and clinical outcomes of subjects following a contact at high/moderate risk of 2019-nCoV transmission. The study population is represented by all subjects who had a contact with laboratory-confirmed 2019-nCoV cases and whose contact was considered to be at high/moderate risk of 2019-nCoV transmission, as defined with precise criteria emitted by the Health Ministry and Santé Publique France. Procedures added by the research: Nasopharyngeal swabs for determination of the presence of 2019-nCoV detected by Polymerase Chain Reaction (PCR). Blood sampling for determination of the presence of 2019-nCoV type M immunoglobulins or type G immunoglobulins by microneutralisation technique.
Description: PCR
Measure: Number of Participants with presence of 2019-nCoV in at least one of nasopharyngeal swab Time: 14 daysDescription: PCR
Measure: For each participant, time (days) between the last contact with the laboratory-confirmed 2019-nCoV case and the first positive PCR Time: 14 daysDescription: PCR
Measure: For each participant, time (days) between the first positive PCR and the first negative PCR Time: 14 daysDescription: Patient Reported Outcome
Measure: Number of Participants with presence of at least one of the following symptoms: fever > 38°C, asthenia/fatigue/malaise, headache, thrills/sweating, myalgia/aches, cough, dyspnea, Acute Respiratory Distress Syndrome, diarrhe Time: 14 daysDescription: microneutralisation assay
Measure: Number of Participants with positive serology in the 90 days following last contact Time: 90 daysBase 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 1The novel coronavirus pneumonia is a kind of new emerging respiratory infectious disease, characterized by fever, dry cough, and chest tightness, and caused by the infection of the 2019 novel coronavirus (2019-nCoV). In severe cases, there will be rapid respiratory system failure. The novel coronavirus pneumonia is extremely contagious and the disease progresses rapidly. It has become a urgent and serious public health event that threatens human life and health globally. Among them, severe pneumonia caused by novel coronavirus is characterized by extensive acute inflammation of the lungs and the patient is critically ill. At present, there is no effective treatment in clinical practice.Most of them should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions. This clinical trial is to inspect the safety and efficiency of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for severe pneumonia patients infected with 2019-nCoV.
Description: Evaluation of Pneumonia Improvement
Measure: Pneumonia severity index Time: From Baseline (0W) to 12 week after treatmentDescription: Evaluation of Pneumonia Improvement
Measure: Oxygenation index (PaO2/FiO2) Time: From Baseline (0W) to 12 week after treatmentDescription: Incidence of acute and chronic treatment-related adverse events in patients with novel coronavirus severe pneumonia receiving UC-MSCs infusion as assessed.
Measure: Side effects in the UC-MSCs treatment group Time: From Baseline (0W) to 96 week after treatmentDescription: Marker for efficacy of treatment
Measure: 28-days survival Time: Day 28Description: Markers of organ function(Score each criterion on a scale of 0 to 4, and the higher the score, the worse the prognosis.)
Measure: Sequential organ failure assessment Time: Day 28Description: Markers of Infection
Measure: C-reactive protein Time: From Baseline (0W) to 12 week after treatmentDescription: Markers of Infection
Measure: Procalcitonin Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: Lymphocyte count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD3+, CD4+ and CD8+ T celll count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD4+/CD8+ratio Time: From Baseline (0W) to 12 week after treatmentCompare the efficacy and safety of Bromhexine Hydrochloride Tablets combined with standard treatment/ standard treatment in patients with suspected and mild, or common novel coronavirus pneumonia (COVID-19). Random, open, group sequential design.
Description: Defined as random to fever, respiratory rate return to normal and cough remission over 48 hours.
Measure: Time to clinical recovery after treatment Time: within 14 days from the start of medicationDescription: Aggravation was defined as(one of them): respiratory distress, RR ≥ 30 times / min; SpO2 ≤ 93% in resting state; arterial partial pressure of oxygen (PaO2) /concentration of oxygen (FiO2) ≤ 300mmHg
Measure: Rate of aggravation Time: within 14 days from the start of medicationDescription: Clinical remission was defined as (one of them): sustained (more than 48 hours) alleviation of illness based on symptom (fever, cough, dyspnea, myalgia, diarrhea and so on) all being absent and no evidence for progression.
Measure: Clinical remission rate Time: within 14 days from the start of medicationDescription: oxygenation index
Measure: Dynamic changes of oxygenation index Time: within 14 days from the start of medicationDescription: time of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery
Measure: Time to cure Time: within 14 days from the start of medicationDescription: proportion of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery among infected patients
Measure: rate to cure Time: within 14 days from the start of medicationDescription: defervescence is defined as below 37 Celcius degrees(ear temperature)
Measure: Time to defervescence Time: within 14 days from the start of medicationThere 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 investigators conduct a randomized, open-label trial to evaluate and compare the safety and efficacy of Xiyanping injection in patients with 2019-nCoV pneumonia.
Description: From the beginning of study drug use to fever, respiratory rate, blood oxygen saturation to normal and cough relief, and maintained for at least 72 hours or more, calculated in hours
Measure: Clinical recovery time Time: Up to Day 14Description: From the beginning of research drug use to body temperature <37.3 ℃ (underarm) or mouth temperature ≤37.5 ° C, or anal or ear temperature ≤37.8 ° C, and maintained for 24h or more
Measure: Complete fever time Time: Up to Day 14Description: Cough score "day + night" from the beginning of study medication to cough ≤ 1 point, and maintained for 24 hours and above
Measure: Cough relief time Time: Up to Day 14Description: From the beginning of the study drug to two consecutive times (sampling interval of at least 1 day)
Measure: Virus negative time Time: Up to Day 14Description: Defined as the proportion of subjects exacerbated during treatment and meeting the diagnostic criteria for severe or critical neocoronavirus pneumonia
Measure: Incidence of severe or critical neocoronavirus pneumonia Time: Up to Day 14The 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 monthIn December 2019, a novel coronavirus infectious disease characterized by acute respiratory impairment due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan city of Hubei province in China. So far no specific antiviral therapy can be available for patients with SARS-CoV-2 infection. Although symptomatic and supportive care, even with mechanical ventilation or extracorporeal membrane oxygenation (ECMO), are strongly recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes. This pilot clinical trial will be performed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in severe patients with novel coronavirus pneumonia (NCP).
Description: Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)
Measure: Adverse reaction (AE) and severe adverse reaction (SAE) Time: Up to 28 daysDescription: Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)
Measure: Time to clinical improvement (TTIC) Time: Up to 28 daysDescription: Number of patients weaning from mechanical ventilation within 28 days
Measure: Number of patients weaning from mechanical ventilation Time: Up to 28 daysDescription: Duration (days) of ICU monitoring within 28 days
Measure: Duration (days) of ICU monitoring Time: Up to 28 daysDescription: Duration (days) of vasoactive agents using within 28 days
Measure: Duration (days) of vasoactive agents usage Time: Up to 28 daysDescription: Duration (days) of mechanical ventilation supply among survivors
Measure: Duration (days) of mechanical ventilation supply Time: Up to 28 daysDescription: Number of patients with improved organ failure within 28 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs
Measure: Number of patients with improved organ failure Time: Up to 28 daysDescription: Rate of mortality within 28 days
Measure: Rate of mortality Time: Up to 28 daysDescription: Records of daily sequential organ failure assessment (SOFA) score (From 0 to 24 points, higher scores mean a worse outcome)
Measure: Sequential organ failure assessment (SOFA) score Time: Every day for 28 daysDescription: Records of Blood routine test
Measure: Lymphocyte Count (10E9/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Coagulation function
Measure: D-dimer (mg/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Records of heart failure
Measure: pro-type B natriuretic peptide (pro-BNP) (pg/ml) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Record of serum cytokine
Measure: IL-1β (pg/ml) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Record of serum cytokine
Measure: IL-2R (ng/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Record of serum cytokine
Measure: IL-6 (ng/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Record of serum cytokine
Measure: IL-8 (ng/L) Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Computed tomography or X-ray
Measure: Chest imaging Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if availableDescription: Time to SARS-CoV-2 RT-PCR negativity in respiratory tract specimens
Measure: Time to SARS-CoV-2 RT-PCR negativity Time: Up to 28 daysThe 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 daysOutbreak of 2019 Novel Coronavirus infection quickly spread to the world. Confirmed patients were isolated and treated in our department. 2019 Novel Coronavirus was detected in multiple organ system. Clinical data was recorded to investigate the its relationship with viral detection.
Description: rate of positive results of detection 2019 Novel Coronavirus nucleic acid from urine, blood, anal swabs and pharyngeal swabs samples
Measure: Positive rate of 2019 Novel Coronavirus RNA Time: 28 daysDescription: If the patient will survive after comprehensive treatment
Measure: Survival rate Time: 28 daysSince december 2019, acute respiratory disease due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. There is no confirmed antivirus therapy for 2019-nCoV infection. Natural killer (NK) cells are innate lymphocytes that may serve as useful effectors against danger infection. The purpose of this clinical investigation is to evaluate the safety and efficiency of NK Cells in combination with standard therapy for pneumonia patients infected with 2019-nCoV.
Description: Evaluation of pneumonia improvement
Measure: Improvement of clinical symptoms including duration of fever Time: Measured from day 0 through day 28Description: Evaluation of pneumonia improvement
Measure: Improvement of clinical symptoms including respiratory frequency Time: Measured from day 0 through day 28Description: Safety evaluation
Measure: Number of participants with treatment-related adverse events evaluated with CTCAE,version 4.0 Time: Measured from day 0 through day 28Description: Marker for 2019-nCoV
Measure: Time of virus nucleic acid test negative Time: Measured from day 0 through day 28Description: Marker of immunological function
Measure: CD4+ and CD8+ T cell count Time: Measured from day 0 through day 28Description: Marker for efficacy of treatment
Measure: Rate of mortality within 28-days Time: Day 28Description: Recovery of lung injury
Measure: Size of lesion area by thoracic imaging Time: Measured from day 0 through day 28Although immune-inflammatory treatment is not routinely recommended to be used for SARS-CoV-2 pneumonia, according to the pathological findings of pulmonary oedema and hyaline membrane formation, timely and appropriate use of immune modulator together with ventilator support should be considered for the severe patients to prevent ARDS development. The sphingosine-1-phosphate receptor regulators Fingolimod (FTY720) is an effective immunology modulator which has been widely used in multiple sclerosis.The aim of this study was to determine whether the efficacy of fingolimod for a novel coronavirus disease (COVID-19).
Description: The lesion change on X-ray images from day 5 to baseline
Measure: The change of pneumonia severity on X-ray images Time: 5 day after fingolimod treatmentThis 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 29As of February 17th, 2020, China has 70635 confirmed cases of coronavirus disease 2019 (COVID-19), including 1772 deaths. Human-to-human spread of virus via respiratory droplets is currently considered to be the main route of transmission. The number of patients increased rapidly but the impact factors of clinical outcomes among hospitalized patients are still unclear.
Description: The primary outcome is the time to negative conversion of coronavirus
Measure: Time to negative conversion of severe acute respiratory syndrome coronavirus 2 Time: 1 monthDescription: The time of hospitalization.
Measure: Length of stay in hospital Time: 1 monthDescription: The rate of survival within hospitalization of these patients will be tracked.
Measure: Survival Time: 1 monthDescription: The rate of intubation within hospitalization of these patients will be tracked.
Measure: Intubation Time: 1 monthSince 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 weeksTo develop practical and effective clinical diagnosis and treatment schemes for the control of novel coronavirus pneumonia.
Description: Number of patients recover from novel coronavirus pneumonia
Measure: recovery Time: up to 24 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 57As of February 17th, 2020, China has 76396 confirmed cases of coronavirus disease 2019 (COVID-19), including 2348 deaths. Although the impact factors of clinical outcomes among hospitalized patients still need to be clarified, some of the therapeutic regimens have shown the potency in the treatment of severe cases. Investigators aim to evaluate the efficacy of psychological and physical rehabilitation based humanistic care in the treatment of COVID-2019.
Description: Time for recovery from admission to discharged
Measure: Recovery Time Time: 1 monthDescription: Self-rating depression scale will be finished from patients by a scale table designed by investigator
Measure: Self-rating depression scale Time: 1 monthDescription: Survival rate of the patient after treatment
Measure: Survival rate Time: 1 monthAs of February 17th, 2020, China has 76396 confirmed cases of coronavirus disease 2019 (COVID-19), including 2348 deaths. The impact factors of clinical outcomes among hospitalized patients still need to be clarified. The healthcare workers faced greater mental and physical pressure under long-term, high-intensity, high-risk working conditions. Investigators aim to evaluate the positive effect of humanistic care for healthcare workers participated in the treatment of COVID-19.
Description: Self-rating depression scale will be finished from healthcare workers by a scale table designed by investigator
Measure: Self-rating depression scale Time: 1 monthDescription: the incidence of post-traumatic stress disorder in healthcare workers
Measure: Incidence of PTSD Time: 1 monthThis is an open-label, randomized, blank-controlled treatment clinical study. The objective of this study is to investigate the effect of T89 on improving oxygen saturation and clinical symptoms in patients with Coronavirus Disease 2019 (COVID-19). In this study, estimated total of 120-240 male and female patients who have been diagnosed with non-critical type of coronavirus pneumonia (COVID-19) will be enrolled and randomly assigned to one of two study groups, the T89 treatment group and the blank control group, to T89 or nothing on the base of a recommended standard treatment for up to 14 days . The primary efficacy parameters include the time to oxygen saturation recovery to normal level (≥97%), the proportion of patients with normal level of oxygen saturation after treatment, and the total duration of oxygen inhalation, oxygen flow change by time, oxygen concentration change by time during treatment.
Description: From screening to the end of treatment, for all patients randomized, oxygen saturation will be assessed for 3 times daily, the time to oxygen saturation recovery to normal level (≥97%) will be calculated finally based on that record and compared between two groups.
Measure: The time to oxygen saturation recovery to normal level (≥97%) Time: Day -1 to 10Description: The proportion of patients with normal level of oxygen saturation(≥97%) after treatment will be calculated finally based on that record and compared between two groups.
Measure: The proportion of patients with normal level of oxygen saturation(≥97%) Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the symptoms will be assessed 2 times daily, and the time to achievement of remission for each symptom will be calculated finally based on the record and compared between two groups.
Measure: The degree of remission of symptoms of patients, including: fatigue, nausea, vomiting, chest tightness, shortness of breath, etc. Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, myocardial enzyme spectrum will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the myocardial enzyme spectrum recovery to normal will be calculated finally based on the record and compared between two groups.
Measure: The time to the myocardial enzyme spectrum recovery to normal after treatment Time: Day -1, 3, 7 and 10Description: From screening to the end of treatment, for all patients randomized, myocardial enzyme spectrum will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal myocardial enzyme spectrum after treatment will be calculated finally based on the record and compared between two groups.
Measure: The proportion of the patients with normal myocardial enzyme spectrum after treatment Time: Day -1, 3, 7 and 10Description: From screening to the end of treatment, for all patients randomized, 12-lead electrocardiogram will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the myocardial enzyme spectrum recovery to normal level will be calculated finally based on the record and compared between two groups.
Measure: The time to the electrocardiogram recovery to normal level after treatment Time: Day -1, 3, 7 and 10Description: From screening to the end of treatment, for all patients randomized, 12-lead electrocardiogram will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal electrocardiogram will be calculated finally based on the record and compared between two groups.
Measure: The proportion of the patients with normal electrocardiogram after treatment Time: Day -1, 3, 7 and 10Description: From screening to the end of treatment, for all patients randomized, the hemodynamics will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the hemodynamics recovery to normal will be calculated finally based on the record and compared between two groups.
Measure: The time to the hemodynamics recovery to normal after treatment Time: Day -1 and 10Description: From screening to the end of treatment, for all patients randomized, the hemodynamics will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal hemodynamics will be calculated finally based on the record and compared between two groups.
Measure: The proportion of the patients with normal hemodynamics after treatment Time: Day -1 and 10Description: From screening to the end of treatment, for all patients randomized, the clinical severity will be assessed 1 time daily. The time to exacerbation or remission of the disease will be calculated finally based on the record and compared between two groups.
Measure: The time to exacerbation or remission of the disease after treatment; Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the clinical severity will be assessed 1 time daily. The proportion of patients whose disease get aggravated or alleviated will be calculated finally based on the record and compared between two groups.
Measure: The proportion of the patients with exacerbation or remission of disease after treatment Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the need for additional treatment will be recorded and compared between two groups.
Measure: The proportion of patients who need other treatment (e.g. heparin, anticoagulants) due to microcirculation disorders Time: Day -1 to 10Description: For all patients, the mortality will be recorded in each group and the rate will be compared between two groups.
Measure: The all-cause mortality rate Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the proportion of patients with acidosis will be compared between two groups based on the hemodynamics results.
Measure: The proportion of patients with acidosis Time: Day -1 and 10Description: For all patients, the duration of hospitalization will be recorded in each group and compared between two groups.
Measure: The total duration of the patients in-hospital Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the total duration of oxygen inhalation during oxygen treatment will be assessed and compared, if applicable, between two groups.
Measure: The total duration of oxygen inhalation during treatment Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the oxygen flow rate during oxygen treatment will be assessed and compared, if applicable, between two groups.
Measure: The oxygen flow rate during treatment Time: Day -1 to 10Description: From screening to the end of treatment, for all patients randomized, the oxygen concentration during oxygen treatment will be assessed and compared, if applicable, between two groups.
Measure: The oxygen concentration during treatment Time: Day -1 to 10The novel coronavirus infectious disease ( COVID-19") induced by novel coronavirus(SARS-CoV-2) in December 2019 has outbreaked in Wuhan. It may lead to epidemic risk in global. As the COVID-19 is an emerging infectious disease, it has not scientifically recognized and has no effective drugs for treatment currently. Therefore, we will launch a scientific project "The efficacy and safety of carrimycin treatment in 520 patients with COVID-19 stratificated clinically: A multicenter, randomized (1:1), open-controlled (one of lopinavir/ritonavir tablets or Arbidol or chloroquine phosphate) study" . We try to establish the criteria for clinical cure and the early predictive model of COVID-19 progression. The primary efficiency outcomes were:(1) Fever to normal time (day); (2) Pulmonary inflammation resolution time (HRCT) (day); and (3)Negative conversion (%) of SARS-CoV-2 RNA at the end of treatment. The secondary efficiency outcomes and adverse events were observed.
Description: Fever to normal time (day)
Measure: Fever to normal time (day) Time: 30 daysDescription: Pulmonary inflammation resolution time (HRCT) (day)
Measure: Pulmonary inflammation resolution time (HRCT) (day) Time: 30 daysDescription: Negative conversion (%) of 2019-nCOVRNA in gargle (throat swabs) at the end of treatment
Measure: Negative conversion (%) of 2019-nCOVRNA in gargle (throat swabs) at the end of treatment Time: 30 daysCOVID-19 caused clusters of severe respiratory illness and was associated with 2% mortality. No specific anti-viral treatment exists. The mainstay of clinical management is largely symptomatic treatment, with organ support in intensive care for seriously ill patients. Cellular therapy, using mesenchymal stem cells has been shown to reduce nonproductive inflammation and affect tissue regeneration and is being evaluated in patients with ARDS. This clinical trial is to inspect the safety and efficiency of mesenchymal stem cells (MSCs) therapy for severe COVID-19.
Description: Evaluation of Pneumonia Improvement
Measure: Size of lesion area and severity of pulmonary fibrosis by chest CT Time: At Baseline , Day 6, Day 10, Day 14, Day 28 and Day 90Description: Evaluation of Pneumonia Improvement No limitation of activities, discharged from hospital =Score 1; Hospitalized, no oxygen therapy=Score 2; Oxygen by mask or nasal prongs-Score 3; Non-invasive ventilation or high-flow oxygen=Score 4; Mechanical ventilation or ECMO=Score 5; Death=Score 6.
Measure: mMRC (Modified Medical Research Council) dyspnea scale Time: Baseline , Day 7, Day 14, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Oxygenation index( PaO2/FiO2) Time: Baseline , Day 7, Day 14, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Duration of oxygen therapy(days) Time: Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Duration of hospitalization(days) Time: Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Blood oxygen saturation Time: Baseline , Day 7, Day 14, Day 28, Day 90Description: Marker of Immunological function
Measure: CD4+ T cell count and cytokine level Time: Baseline , Day 6, Day 10, Day 14, Day 21, Day 28, Day 90Description: Proportion of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measure: Side effects in the MSCs treatment group Time: Baseline , Day 3, Day 6,Day 10, Day 14, Day 21, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: 6-minute walk test Time: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Maximum vital capacity (VCmax) Time: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90Description: Evaluation of Pneumonia Improvement
Measure: Diffusing Capacity (DLCO) Time: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90Covid-19 has spread rapidly throughout the world causing widespread panic, death, and injury. While this virus is the provocateur, it is often the patient's own disproportionate immune response which deals the most devastating (and often fatal) damage. A specific part of the immune system, known as the complement, has been shown to cause such damage in other types of coronaviruses. In the SOLID-C19 study, Soliris (Eculizumab) will be used to modulate the activity of the distal complement preventing the formation of the membrane attack complex. By modulating this portion of the immune response, mortality can be halted while the patient has time to recover from the virus with supportive medical care.
The 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 daysObjects: The purpose of this study was to observe the characteristics of morbidity, disease progression and therapeutic effects of 2019-novel coronavirus pneumonia patients with different clinical types. Method: A single center, retrospective and observational study was used to collect COVID-19 patients admitted to Wuhan Infectious Diseases Hospital (Wuhan JinYinTan Hospital) from January 2020 to March 2020. The general information, first clinical symptoms, hospitalization days, laboratory examination, CT examination, antiviral drugs, immune enhancers, traditional Chinese medicine treatment and other clinical intervention measures were recorded, and the nutritional status and prognosis of the patients were recorded. confirm COVID-19 's disease progression, clinical characteristics, disease severity and treatment effects. To compare the characteristics of disease progression, clinical features, disease severity and therapeutic effect of different types of COVID-19. Outcomes: The characteristics of disease progression, clinical features, disease severity and therapeutic effect of different types of COVID-19. Conclusion: The characteristics of disease progression, clinical features and therapeutic effect of different types of COVID-19.
Description: The mortality of COVID-19 in 28 days
Measure: Mortality Time: 28 dayDescription: The time interval of COVID-19 form nucleic acid confirmed to the nucleic acid detection turn into negative.
Measure: The time interval of Nucleic acid detection become negative Time: 28 dayThere is still no effective antiviral drugs and vaccines against SARS-CoV-2 yet now. This is an obsevational study, the investigators collected the clinical information and clinical outcomes of the COVID-19 patients using anti-2019-nCoV inactivated convalescent plasma.The study is to evaluate the efficacy and safety of anti-2019-nCoV inactivated convalescent plasma in the treatment of COVID-19 pneumonia.
Description: The SARS-CoV-2 nuclei acid was quantified using RT-PCR
Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 1 Time: 1 day after receiving plasma transmissionDescription: Clinical outcomes include death, critical illness, recovery
Measure: Numbers of participants with different Clinical outcomes Time: From receiving plasma transmission to 4 weeksNew coronavirus infection is an important cause of public health emergencies at home and abroad, which seriously affects people's health and social stability. The outbreak of SRAR-COV in China in 2003 caused serious social impact. From January 2002 to August 7, 2003, there were a total of 8,422 cases worldwide, involving 32 countries and regions, of which 919 cases were fatal, with a fatality rate of nearly 11%. The fatality rate of elderly patients and patients with underlying diseases was even more high.There is no precise and effective treatment for coronavirus infection. In vitro, IFN-α2β has inhibitory effects on MERS-CoV and closely related coronavirus severe acute respiratory syndrome (SARS) -CoV. A study showed the effects of interferon-α2β and ribavirin on the replication of nCoV isolates hCoV-EMC / 2012 in Vero and LLC-MK2 cells. The combined application may be useful for the management of patients with nCoV infection in the future. At present, the combination therapy of interferon α2β and ribavirin has been successfully applied in the initial treatment and prevention of SARS and MERS.The purpose of this study was to evaluate the efficacy and safety of recombinant human interferon α1β in treating patients with new coronavirus infection in Wuhan.
Description: dyspnea
Measure: The incidence of side effects Time: Within 14 days after enrollmentDescription: SPO2≤94%
Measure: The incidence of side effects Time: Within 14 days after enrollmentDescription: respiratory rate ≥24 breaths/min in oxygen state)
Measure: The incidence of side effects Time: Within 14 days after enrollmentDescription: the patient had a normal body temperature of > for 24 hours (without taking antipyretic drugs or hormones) without self-consciousness Dyspnea or reduced dyspnea;
Measure: Time from patient enrollment to clinical remission Time: Within 14 days after enrollmentDescription: Proportion of patients with normal body
Measure: Proportion of patients with normal body Time: Within 14 days after enrollmentDescription: Proportion of patients without dyspnea
Measure: Proportion of patients without dyspnea Time: Within 14 days after enrollmentDescription: Proportion of patients without cough
Measure: Proportion of patients without cough Time: Within 14 days after enrollmentDescription: Proportion of patients without oxygen treatment
Measure: Proportion Time: Within 14 days after enrollmentDescription: The negative conversion rate of new coronavirus nucleic acid
Measure: The negative conversion rate of new coronavirus nucleic acid Time: Within 14 days after enrollmentDescription: Proportion of patients hospitalized/hospitalized in ICU
Measure: Proportion Time: within 28 days after enrollmentDescription: Frequency of serious adverse drug events.
Measure: Frequency of serious adverse drug events. Time: within 28 days after enrollmentIn 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 28A randomized controlled trial in which nurses will be randomized to either medical masks or N95 respirators when providing care to patients with COVID-19.
Description: Number of participants with RT-PCR confirmed COVID-19 infection
Measure: RT-PCR confirmed COVID-19 infection Time: 6 monthsDescription: Number of participants with acute respiratory illness
Measure: Acute respiratory illness Time: 6 monthsDescription: Number of participants with absenteeism
Measure: Absenteeism Time: 6 monthsDescription: Number of participants with lower respiratory infection
Measure: Lower respiratory infection Time: 6 monthsDescription: Number of participants with pneumonia
Measure: Pneumonia Time: 6 monthsDescription: Number of participants with ICU admission
Measure: ICU admission Time: 6 monthsDescription: Number of participants needing mechanical ventilation
Measure: Mechanical ventilation Time: 6 monthsDescription: Number of participants that died
Measure: Death Time: 6 monthsCurrently, 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 weeksDisease caused by 2019 Novel Coronavirus also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
The study is a double-blind, randomised, placebo-controlled trial that will be conducted in healthcare settings. After obtaining fully informed consent, the investigator will recruit healthcare workers in a healthcare facility delivering direct care to patients with either proven or suspected COVID-19, who can be followed reliably for up to 5 months. 40,000 participants will be recruited and the investigators predict an average of 400-800 participants per site in 50-100 sites. The participant will be randomised in Asia to receive either chloroquine or placebo (1:1 randomisation) or in European and African sites, to receive hydroxychloroquine or placebo (1:1 randomisation). A loading dose of 10mg base/kg (four 155mg tablets for a 60kg subject), followed by 155 mg daily (250mg chloroquine phosphate salt/ 200mg hydroxychloroquine sulphate) will be taken for 90 days. If the participant is diagnosed with COVID-19, they will take continue to take the study medication unless advised to stop by their healthcare professional, or 90 days after enrolment, whichever is sooner. Episodes of symptomatic respiratory illness, including symptomatic COVID-19, and clinical outcomes will be recorded in the Case Record Form during the follow-up period.
Description: Number of symptomatic COVID-19 infections will be compared between the chloroquine or hydroxychloroquine and placebo groups
Measure: Number of symptomatic COVID-19 infections Time: Approximately 90 daysDescription: Symptoms severity of COVID-19 will be compared between the two groups using a respiratory severity score.
Measure: Symptoms severity of COVID-19 Time: Approximately 90 daysDescription: Number of asymptomatic cases of COVID-19 will be determined by comparing serology in all participants at time of enrolment and at the end of follow up.
Measure: Number of asymptomatic cases of COVID-19 Time: Approximately 90 daysDescription: Number of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.
Measure: Number of symptomatic acute respiratory illnesses Time: Approximately 90 daysDescription: Severity of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.
Measure: Severity of symptomatic acute respiratory illnesses Time: Approximately 90 daysDescription: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, Acute Respiratory Infection and disease severity.
Measure: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity. Time: Approximately 90 daysDescription: Number of days lost to work in relation to the treatment arm
Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on number of days lost to work during the pandemic. Time: Approximately 90 daysDescription: The trial will collect data on monetary costs associated with the use of healthcare resources and determine the effects between treatment groups.
Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on healthcare costs Time: Approximately 90 daysDescription: The trial will collect data on health-related quality of life using the quality of life questionnaire (EQ-5D-3L) to determine the effects between treatment groups.
Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on quality of life measures using the quality of life questionnaire (EQ-5D-3L) Time: Approximately 90 daysThe 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 daysThe investigators plan to conduct a cross-sectional survey to examine how social media use during COVID-19 relates to: (1) information management, (2) assessment of the situation, and (3) affect.
Description: 3 items on fear of the situation, confidence the government can manage the situation, and assessed chance of being infected (each rated using 4-point scales: min = 1, max = 4; higher scores indicate increased confidence / likelihood / fear)
Measure: Assessment of COVID-19 situation Time: Single measurement (upon study enrolment)Description: 21-item validated scale assessing symptoms of depression, anxiety, and stress (DASS-21): Min score = 0, Max score = 21; higher score indicates a worse outcome
Measure: Depression, Anxiety and Stress Scale Time: Single measurement (upon study enrolment)Description: Participants' self-report of their familiarity (yes/no) and belief of specific (yes/no), and whether they shared these on social media (yes/no)
Measure: Familiarity and trust in COVID-related rumours Time: Single measurement (upon study enrolment)Description: Participants' assessment of how many cases there have been in COVID-19 and SARS
Measure: Availability heuristic Time: Single measurement (upon study enrolment)Severe 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 monthIn vitro studies revealed that lopinavir/ritonavir and hydroxychloroquine have antiviral activity against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is no clinical studies on the reduction of viral load in patients with COVID-19. This study investigate whether lopinavir/ritonavir or hydroxychloroquine reduces viral load from respiratory specimen in patients with mild COVID-19.
Description: Area under the curve (AUC) of Ct value or viral copies number per mL
Measure: Viral load Time: hospital day 3, 5, 7, 10, 14, 18Description: Viral load change (log10 viral load assessed by reverse transcription-PCR) during hospital day 3, 5, 7, 10, 14, 18)
Measure: Viral load change Time: hospital day 3, 5, 7, 10, 14, 18Description: Time to clinical improvement (TTCI) is defined as the time to normalization of fever, respiratory rate, and oxygen saturation, and alleviation of cough within at least 72 hours
Measure: Time to clinical improvement (TTCI) Time: up to 28 daysDescription: Percentage of progression to supplemental oxygen requirement by day 7
Measure: Percentage of progression to supplemental oxygen requirement by day 7 Time: hospital day 7Description: Time to NEWS2 (National Early Warning Score 2) of 3 or more maintained for 24 hours by day 7
Measure: Time to NEWS2 (National Early Warning Score 2) of 3 or more maintained for 24 hours by day 7 Time: hospital day 7Description: Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission
Measure: Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission Time: up to 28 daysDescription: Rate of switch to Lopinavir/ritonavir or hydroxychloroquine by day 7
Measure: Rate of switch to Lopinavir/ritonavir or hydroxychloroquine by day 7 Time: hospital day 7Description: Safety and tolerability, as assessed by adverse effects
Measure: adverse effects Time: up to 28 daysDescription: Concentration of Lopinavir/ritonavir and hydroxychloroquine
Measure: Concentration of Lopinavir/ritonavir and hydroxychloroquine Time: 1, 2, 4, 5, 12 hours after taking intervention medicineStudy 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 daysOur project intends to independently develop a fully enclosed rapid detection system for a total of 22 pathogens, including SARS-CoV-2, on the basis of the QIAstat-Dx fully automatic multiple PCR detection platform. The reasonably designed experiments are used to verify the performance of the cartridge detection and prove its clinical application value. The 22 pathogens tested in this project includes 4 coronavirus subtypes, A / B flu, parainfluenza virus, respiratory syncytial virus, etc., which is of great significance for the differential diagnosis of similar patients.
Novel 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 daysAll patients with COVID-19 were divided into three groups according to their illness: mild patient who receive conventional oxygen therapy, severe patients who receive nasal high flow oxygen inhalation or non-invasive positive pressure ventilation,all the oxygen therapy will be used as part of the standard of care. Each group will enroll 10 patients, the treatment of all patients will be continuously optimized during observation, and the incidence of respiratory failure, intubation rate, 28 day mortality rate, ICU hospitalization days, etc will be recorded and analyzed so to optimize the treatment time window of sequential oxygen therapy
Description: Incidence of respiratory failure at day 28 after enrollment
Measure: Incidence of respiratory failure Time: 28 dayDescription: mortality rate at day 28 after enrollment
Measure: 28 day mortality rate Time: 28 dayThousands 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 daysCovid-19 causes a range of symptoms and clinical trajectories. There are uncertainties related to what risk factors and comorbity profiles that associate with development of adverse outcomes,i.e. a acute respiratory disetress syndrome (ARDS) and diffuse alveolar damage, and mortality. This study aims to identify organ specific biomarkers, viral dynamics and immuneresponse in patients in patients infected with SARS-CoV2.
Complete the examination of cardio-pulmonary ultrasound in accordance with the a-ccue process of patients with novel coronavirus bedside. To summarize and analyze the characteristics of cardiopulmonary ultrasound in patients with novel coronavirus pneumonia, and assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis. Auto line B is a method which is based on artificial intelligence is used to calculate the lungs ultrasonic B line numbers reviewing the status of patients with lung, and also evaluate patients' lungs using the traditional artificial semi-quantitative method, to evaluate those two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not, and verify consistency of ultrasonic evaluation method and the way of CT evaluation.
Description: Complete the examination of cardio-pulmonary ultrasound in accordance with the a-ccue process of patients with novel coronavirus bedside. To summarize and analyze the characteristics of cardiopulmonary ultrasound in patients with novel coronavirus pneumonia
Measure: characteristics of cardiopulmonary ultrasound Time: 30 minsDescription: assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis.
Measure: assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis. Time: 2-3weeksDescription: Auto line B is a method which is based on artificial intelligence is used to calculate the lungs ultrasonic B line numbers reviewing the status of patients with lung, and also evaluate patients' lungs using the traditional artificial semi-quantitative method, to evaluate those two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not
Measure: evaluate two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not, and verify consistency of ultrasonic evaluation method and the way of CT evaluation. Time: 3 hoursThe outbreak of Covid-19 started several clinical trials and treatment experiments all over the world in the first months of 2020. This study investigates reports of adverse events related to used molecules, including but not limited to protease inhibitors (lopinavir/ritonavir), chloroquine, azithromycin, remdesivir and interferon beta-1a. Analyses of reports also include the International classification of disease ICD-10 for treatments in the World Health Organization (WHO) global Individual Case Safety Report (ICSR) database (VigiBase).
Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Renal failure Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Heart failure Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: EKG disturbance Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Hepatic failure Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Anemia Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Leucopenia Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Vascular disease Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Toxidermia Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Osteoarticular adverse event Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Death Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Acute respiratory distress syndrome Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020Description: defined by the Medical Dictionary for Regulatory Activities (MeDRA) terms
Measure: Pulmonary embolism or pulmonary hypertension Time: Case reported in the World Health Organization (WHO) database of individual safety case reports to 17/03/2020The Novel Coronavirus (2019-nCoV), also known as Wuhan coronavirus, causes the 2019-nCoV acute respiratory disease. The number of patients infected by 2019-nCoV in Italy closely followed an exponential trend, and Italy reported the highest number of infected patients and deaths in the world excluding China.
Description: different maternal and perinatal outcomes were evaluated including: admission to ICU, use of mechanical ventilation, maternal death, early pregnany loss, perinatal death, intrauterine growth restriction (IUGR), preterm birth, mode of delivery, LBW, admission to neonatal ICU (NICU), and clinical or serologic evidence of vertical trasmission
Measure: Maternal and perinatal outcomes Time: during gestation and at the time of delivery of the babyDouble 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 daysThe study is designed as a randomized, placebo-controlled, double blind, multicenter, Phase III trial to compare two COVID-19 treatment regimens in hospitalized adult subjects who are diagnosed with severe COVID 19. Arm A: CD24Fc/Best Available Treatment; Arm B: placebo/ Best Available Treatment. CD24Fc will be administered as single dose of 480 mg via IV infusion on Day 1. Total of 230 subjects will be enrolled and randomized in 1:1 ratio to receive CD24Fc or placebo. All subjects will be treated with the best available treatment. The follow up period is 28 days.
Description: Time to improve in clinical status: the time (days) required from the start of treatment to the improvement of clinical status "severe" to "moderate/mild"; or improvement from "scale 3 or 4" to "scale 5 or higher" based on NIAID ordinal scales.
Measure: Improvement of COVID-19 disease status Time: 14 daysDescription: Time for disease progression from NIAID scale 3 or 4 to scale 2 or 1, and patients need to be on invasive mechanical ventilation, or ESMO, or death.
Measure: Disease progression of COVID-19 Time: 28 daysDescription: All cause of death
Measure: All cause of death Time: 28 daysDescription: Conversion rate of clinical status on days 8 (proportion of subjects who changed from "severe" to "moderate or mild", or the improvement from "scale 3 or 4" to "scale 5 or higher" on NIAID ordinal scale)
Measure: Conversion rate of clinical status at Day 8 Time: 7 daysDescription: Conversion rate of clinical status on days 15 (proportion of subjects who changed from "severe" to "moderate or mild", or the improvement from "scale 3 or 4" to "scale 5 or higher" on NIAID ordinal scale)
Measure: Conversion rate of clinical status at Day 15 Time: 14 daysDescription: The discharge time or NEWS2 (National Early Warning Score 2) of ≤2 is maintained for 24 hours
Measure: Hospital discharge time Time: 28 daysDescription: Duration of mechanical ventilation (IMV, NIV) (days)
Measure: Duration of mechanical ventilation Time: 28 daysDescription: Duration of pressors (days)
Measure: Duration of pressors Time: 28 daysDescription: Duration of extracorporeal membrane oxygenation (days)
Measure: Duration of ECMO Time: 28 daysDescription: Duration of oxygen therapy (oxygen inhalation by nasal cannula or mask) (days)
Measure: Duration of oxygen therapy Time: 28 daysDescription: Length of hospital stay (days)
Measure: Length of hospital stay Time: 28 daysDescription: Changes of absolute lymphocyte count in peripheral blood
Measure: Absolute lymphocyte count Time: 28 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 overall purpose of this project is to better understand the incidence, risk factors, etiology, clinical manifestations and outcome of tCOVID19 in solid organ transplant recipients. The results obtained will allow us to gain insight on the need of antiviral treatment, on the strategy for complications surveillance, on how to adjust the immunosuppressant therapy and on the level of care in which each patient should be treated. In order to attain the objectives previously described we will develop a multicenter prospective study of consecutive cases of COVID-19 among solid organ transplant recipients.
Description: Number of Solid Organ Transplant Recipients positive to coronavirus
Measure: Incidence of coronavirus infection in Solid Organ Transplant Recipients Time: From baseline at the time of signature of informed consent form to day 28 after confirmation of positive test to coronavirusDescription: Number of participants who present clinical symptoms possibly related to coronavirus infection in Solid Organ Transplant Recipients
Measure: Clinical manifestations of coronavirus infection in Solid Organ Transplant Recipients Time: From baseline at the time of signature of informed consent form to day 28 after confirmation of positive test to coronavirusDescription: Gathering possible risk factors in coronavirus infection in Solid Organ Transplant
Measure: Presence of other risk factors Time: From baseline at the time of signature of informed consent form to day 28 after confirmation of positive test to coronavirusDescription: Establish the frequency and type of complications related to the net state of the patient immunosuppression
Measure: Establish the frequency and type of complications related to the net state of the patient immunosuppression Time: From baseline at the time of signature of informed consent form to day 28 after confirmation of positive test to coronavirusDescription: Another infections at the time of coronavirus positive infection will be gathered
Measure: Frequency of co-infections Time: From baseline at the time of signature of informed consent form to day 28 after confirmation of positive test to coronavirusDescription: Number of deaths in coronavirus infection in Solid Organ Transplant
Measure: Mortality Time: From baseline at the time of signature of informed consent form to study completionDescription: Biochemical analysis, hemogram,
Measure: Laboratory characteristics Time: At inclusion and at 28 days of follow upDescription: Nasopharyngeal swabs
Measure: Determination of coronavirus viral load Time: At inclusion at 14 days and at 28 daysDescription: According to the clinical manifestations at blood culture, pleural liquid culture, gram stain and culture of sputum, detection of pneumococcus and Legionella pneumophila antigen in urine, in cases of pneumonia
Measure: Microbiological testing Time: At inclusion at 14 days and at 28 daysThe aim of our study is to investigate the physical activity, quality of life and stress levels of individuals living in their homes isolated due to coronavirus (COVID-19) disease. The last three sections of the International Physical Activity Questionnaire (IPAQ) will be used to evaluate the current physical activity level of the participants. Parameters such as housework, home care and family care, rest, sports and leisure physical activities, sitting time will be evaluated. Short Form 12 (Short Form12- SF12) quality of life scale will be used to evaluate health-related quality of life. Beck Depression Scale will be applied to investigate the stress levels of the individuals participating in our study.
Description: The International Physical Activity Questionnaire (IPAQ) will be used to evaluate the current physical activity level of the participants. The survey validity and reliability studies have been conducted in Turkey by Ozturk. The survey consists of 27 questions and 5 parts.
Measure: International Physical Activity Questionnaire (IPAQ) Time: 4 weeksDescription: Short Form 12 (Short Form12- SF12) quality of life scale will be used to evaluate health-related quality of life. SF-12 is an easy-to-apply 12-question scale that has been validated and reliable and obtained by shortening and simplifying SF-36, which evaluates the last 4 weeks.
Measure: Health-Related Quality of Life SF-12 Scale Time: 4 weeksDescription: The individuals participating in our study will be evaluated with the Beck Depression Scale developed in 1961 by Beck et al. The scale validity and reliability studies have been conducted in Turkey by Hisli. The scale is a likert-type scale consisting of 21 items, each scored between 0-3.
Measure: Beck Depression Scale Time: 4 weeksThis study is a multi-centered, three-armed, randomized, double-blinded, controlled study, namely, the oral trial drug favipiravir tablets plus chloroquine phosphatetablets tablets group (combined group), the oral trial drug favipiravir tablets group (pirovir group), and the oral placebo treatment group (control group). The total number of enrolled cases in this study was set at 150. During the treatment, the clinical data of the subjects were collected, the changes of viral load and biochemical indicators were detected, and the outcome of the subjects was monitored. The main indicators of efficacy include improvement or recovery of respiratory symptoms and viral nucleic acid shedding. The rate of progression to severe disease, duration of fever, peripheral blood index and improvement time of pulmonary imaging were the secondary indicators to evaluate the efficacy. Statistical analysis was performed at the middle and final stages of the study to evaluate the efficacy and safety of favipiravir tablets combined with chloroquine phosphatetablets tablets in the treatment of novel coronavirus pneumonia.
Description: Time of improvement or recovery of respiratory symptoms
Measure: Time of Improvement or recovery of respiratory symptoms Time: 10 days during the intervention periodDescription: Number of days from positive to negative for test of swab or sputum virus nucleic acid
Measure: Number of days virus nucleic acid shedding Time: 10 days during the intervention periodDescription: Frequency of improvement or recovery of respiratory symptoms
Measure: Frequency of Improvement or recovery of respiratory symptoms Time: 10 days during the intervention periodDescription: Duration of fever after recruitment
Measure: Duration of fever Time: 10 days during the intervention periodDescription: Disease is defined as severe if it meets any of the following criteria: 1.Respiratory rate ≥30/min; 2. Oxygen saturation ≤93%; 3. Arterial partial oxygen pressure (PaO2)/oxygen absorption concentration (FiO2) ≤300 mmHg (1 mmHg=0.133 kPa)
Measure: Frequencies of progression to severe illness Time: 10 days during the intervention periodDescription: Time of improvement of pulmonary imaging
Measure: Time of improvement of pulmonary imaging Time: 10 days during the intervention periodDescription: Peripheral blood c-reactive protein concentration
Measure: Peripheral blood c-reactive protein concentration Time: day-1,3,7,14 after the intervention periodDescription: Absolute value of peripheral blood lymphocytes
Measure: Absolute value of peripheral blood lymphocytes Time: day-1,3,7,14 after the intervention periodDescription: percentage of peripheral blood lymphocytes
Measure: percentage of peripheral blood lymphocytes Time: day-1,3,7,14 after the intervention periodThe 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 daysThe project is an epidemiological observational study based on an electronic questionnaire on risk factors for COVID-19 in the community and healthcare setting.
Description: Diagnosed with serology or direct viral detection
Measure: Rate of COVID-19 infection Time: 1 yearSARS-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 weeksBackground: During the current COVID-19 pandemic there is urgent need for information about the natural history of the infection in non-hospitalized patients, including the severity and duration of symptoms, and outcome from early in the infection, among different subgroups of patients. In addition, a large, real-world data registry can provide information about how different concomitant medications may differentially affect symptoms among patient subgroups. Such information can be invaluable for clinicians managing chronic diseases during this pandemic, as well as identify interventions undertaken in a naturalistic setting that have differential effects. Such factors may include patient diet, over the counter or prescription medications, and herbal and alternative treatments, among others. Identifying the natural disease history in patients from different demographic and disease subgroups will be important for identifying at-risk patients and effectiveness of interventions undertaken in the community. Objectives: The purpose of this study is to understand at the population level the symptomatic course of known or suspected COVID-19 patients while sheltering-in-place or under quarantine. Symptoms will be measured using a daily report derived from the CTCAE-PRO as well as free response. Outcomes will be assessed based on the duration and severity of infection, hospitalization, lost-to-follow-up, or death. As a patient-centric registry, patients themselves may propose, suggest, and/or submit evidence or ideas for relevant collection.
Description: Daily survey of symptoms known or reported to be associated with COVID-19 infection based including: Headache, Sore throat, Runny nose, Stuffy nose, Gritty/itch eyes, Watery eyes, Nausea, Vomiting, Diarrhea, Sneezing, Coughing, Shortness of breath, Difficulty breathing, Pain or pressure in your chest, Fever, Chills, Body aches, Fatigue, or other issues. Symptoms are rated by participants on a scale of none, mild, moderate, severe, or very severe.
Measure: Define Natural Symptom Course Time: Cumulative symptom score from first onset of symptoms to resolution of symptoms (realistic timeframe of 14 days)Description: Time (in days) from onset of symptoms to hospitalization
Measure: Time to Hospitalization Time: Realistic timeframe of 14 daysDescription: Time (in days) from onset of symptoms to resolution of symptoms
Measure: Time to Symptomatic Recovery Time: Realistic timeframe of 14 daysThe additional effect of personalized health education compared to general education following the internationally accepted principles will be evaluated in the prevention of the serious course of the novel coronavirus infection. It is hypothesised that personalized health education provides a greater degree of lifestyle change, thus the risk of a serious course of infection decreases.
Description: The primary endpoint will be the composite of the rate of the followings in COVID-19 positive cases (verified by an accredited laboratory): the number of pariticipants with ICU (intensive care unit) admission; 48 hours of hospitalisation and/or death. 48 hours of hospitalisation for the following reasons: (I) arrhythmia (causing hemodynamic instability and requiring continuous monitoring and/or cardiac support, as indicated by mean arterial pressure <65 mm Hg, and/or serum lactate >2 mmol/L) and/or (II) Acute Respiratory Distress Syndrome (ARDS): severe hypoxaemic respiratory failure indicated by a Partial Pressure of Oxygen (PaO2)/Fraction of inspired oxygen (FiO2) <300 mmHg according to the Berlin definition and/or (III) circulatory shock (the requirement of continuous vasopressor support to maintain mean arterial pressure <65 mmHg and/or serum lactate >2 mmol/L)
Measure: Primary composite rate of intensive care unit (ICU) admission, 48 hours of hospital admission, death in COVID-19 positive cases Time: 12 monthsDescription: The number of participants, who required general practitioner visit assessed by the investigator.
Measure: The number of general practitioner visits Time: 12 monthsDescription: The number of participants, who required the admission to each type of level of care assessed by the investigator.
Measure: The number of emergency, hospital admission and intensive care admission Time: 12 monthsDescription: The time spent in hospital and on the intensive care unit in days collected at the end of the trial from medical records.
Measure: Length of hospitalization and intensive care unit stay Time: 12 monthsDescription: The number of cases, where the organ dysfunction (central nervous system, cardiovascular, respiratory, renal, liver, hematological) was present, measured daily during the hospital stay , assessed by the physician at the hospital/ICU.
Measure: Organ dysfunction Time: 12 monthsDescription: The reached changes in lifestyle including mental and physical status will be assessed by a questionnaire. The questions related to the coronavirus epidemic in will cover in 3 fields: concerns for self, concerns for family, feeling of being overwhelmed on account of news on the epidemic. The answers can be given by a scale ranging from 1-10 points. Higher score indicates greater level of distress. One question assessess the subjective feeling of being supported, where yes indicates adequate feeling of support and no indicates feeling of being unsupported and/or lonely.
Measure: Lifestyle changes Time: 12 monthsDescription: The financial demand of the treatment of COVID-19 infection spent on each patient will be calculated by a healthcare economist after the trial is completed.
Measure: The cost of care Time: 12 monthsInvestigational medications adjunct to clinical standard of care treatment will be assessed to evaluate safety and effectiveness as an anti-COVID-19 treatment. All hospitalized persons with moderate to severe COVID-19 disease that meet eligibility criteria will be offered participation.
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: Clinical status of subject at day 15 (on a 7 point ordinal scale). Time: Up to 15 daysDescription: 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: Status on an ordinal scale assessed daily while hospitalized and on days 15 and 29 and 180. Time: Up to 180 daysDescription: Time to clinical improvement is defined as the time to normalization of respiratory rate, fever, and oxygen saturation, and alleviation of cough within 72 hours.
Measure: Length of time to clinical improvement Time: Up to 29 daysDescription: Time to clinical progression, defined as the time to death, mechanical ventilation, or ICU admission
Measure: Length of time to clinical progression Time: Up to 29 daysDescription: Fever normalization as defined by: Temperature < 36.6 °C armpit, < 37.2 °C oral, or < 37.8 °C rectal sustained for minimum 24 hours
Measure: Length of time to normalization of fever Time: Up to 29 daysDescription: Oxygen normalization as defined by: peripheral capillary oxygen saturation (Sp02) > 94% sustained minimum 24 hours.
Measure: Length of time to normalization of oxygen saturation Time: Up to 29 daysCoronavirus (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 pneumonia due to a novel coronavirus (SARS-CoV-2) emerged in the city of Wuhan, in China. In a few weeks, the number of confirmed cases of SARS-CoV-2 infection has dramatically increased, with almost 150'000 cases and more than 6'000 reported deaths on March, 16th 2020. Little is known on the rate of human-to-human transmission of this new coronavirus SARS-CoV-2 in the community and within the hospital. Depending on the country, contact subjects considered to be at high or moderate risk of SARS-CoV-2 are, either isolated at home for a period of time defined by the health authorities or, on the contrary, continue their professional activity on the condition that they adopt measures to prevent transmission to those around them. In most European countries, healthcare workers adopt this second option. In all cases, it is most often recommended that contact persons monitor their state of health and communicate it to the persons dedicated to this action. Whether such subjects become spreaders of the virus is not known, nor is the proportion of viral spreader who will develop a symptomatic infection. In this study, we aim to evaluate the virological and clinical outcomes of subjects following a contact at high/moderate risk of SARS-CoV-2 acquisition, in community-subjects and/or healthcare workers. The study population is represented by all subjects who had a contact with laboratory-confirmed SARS-CoV-2 cases and whose contact was considered to be at high/moderate risk of SARS-CoV-2 acquisition. This include both children and adult subjects, subject without social security, and healthcare workers. Procedures added by the research: Blood sampling for determination of the presence of SARS-CoV-2 type M immunoglobulins or type G immunoglobulins by microneutralisation technique. Blood sampling for whole exome sequencing
Description: microneutralisation assay
Measure: Number of Participants with positive serology in the 90 days following last contact Time: 90 daysDescription: Patient Reported Outcome
Measure: fever > 38°C, asthenia/fatigue/malaise, headache, thrills/sweating, myalgia/aches, cough, dyspnea, Acute Respiratory Distress Syndrome, diarrhea Time: 90 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 daysAcute lung injury represents the most severe form of the viral infection sustained by coronavirus disease 2019 (Covid-19) also named as SARS-CoV-2, a new virus emerged in December 2019 in Wuhan (China). The diagnosis is clinical and patients develop flu-like syndrome with fever and cough; patients with clinical symptoms can perform a swab test for diagnosis of positivity to Covid-19. Even if diagnosis and treatment are well described, to date, this viral pandemic infection induces an increased mortality in the world. The aim of the present project is to evaluate specific biomarkers that could be used for patient stratification and for tailor therapy in COVID-19 infected patients.
Description: Change in biomarkers (microRNAs, oxidative stress, IL-2, IL-6, TNF-alfa, leukocytes, subtypes lymphocytes) in covid-19 positive patients vs covid-negative patients
Measure: Biomarkers expression Time: up to 30 daysDescription: Change in CYP450 expression in covid-19 positive patients that develop adverse drug reactions or drug inefficacy
Measure: Liver Biomarkers expression Time: up to 30 daysDescription: Changes in biomarkers in covid-19 patients before and after standard treatment
Measure: biomarkers expression (microRNAs, oxidative stress, IL-2, IL-6, TNF-alfa, leukocytes, subtypes lymphocytes) after treatment Time: 60 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 randomizationThe novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) has been discovered recently in December 2019 from wuhan city in China to spread in more than 40 countries allover the world. This disease has gain the attention of all nations after it has been stated as a pandemic by the World Health Organization (WHO) in March 12, 2020. Currently no treatment has been proved to be efficient in the treatment of infected patients by COVID-19. Natural honey has been demonstrated as potent antimicrobial in many research investigations and has been considered a good alternative for antiviral drugs for the treatment of some viral infections. The investigators aim to study the efficacy of natural honey in the treatment of COVID-19 patients in this randomized , multicenter, controlled trial, comparing honey in one arm to standard care in the other arm.
Description: Percentage of patients turned from positive to negative swaps at day 14
Measure: Rate of recovery from positive to negative swaps Time: 14 daysDescription: Number of days till no fever
Measure: Fever to normal temperature in days Time: 14 daysDescription: Number of days till lungs recovery in chest X ray or CT
Measure: Resolution of lung inflammation in CT or X ray Time: 30 daysDescription: mortality rate in each group at 30 days
Measure: 30 days mortality rate Time: 30 daysDescription: Number of days from initiation of intervention till changing of the swap test result from positive to negative
Measure: Number of days till reaching negative swab results Time: 30 daysIn 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 daysCovidSurg will capture real-world international data, to determine 30-day mortality in patients with COVID-19 infection who undergo surgery. This shared international experience will inform the management of this complex group of patients who undergo surgery throughout the COVID-19 pandemic, ultimately improving their clinical care.
Description: Death up to 30-days post surgery
Measure: 30-day mortality Time: 30 daysDescription: Death up to 7-days post surgery
Measure: 7-day mortality Time: 7 days post surgeryDescription: Reoperation up to 30-days post surgery
Measure: 30-day reoperation Time: Up to 30-days post surgeryDescription: Admission to ICU post surgery
Measure: Postoperative ICU admission Time: Up to 30 days post surgeryDescription: Respiratory failure post surgery
Measure: Postoperative respiratory failure Time: Up to 30 days post surgeryDescription: Acute respiratory distress syndrome post surgery
Measure: Postoperative acute respiratory distress syndrome (ARDS) Time: Up to 30 days post surgeryDescription: Sepsis post surgery
Measure: Postoperative sepsis Time: Up to 30 days post surgeryEvaluate the efficacy of treatment with high-titer Anti- SARS-CoV-2 plasma versus control (SARS-CoV-2 non-immune plasma) in subjects exposed to Coronavirus disease (COVID-19) at day 28.
Description: The cumulative incidence of composite outcome of disease severity will be used in assessing the efficacy of treatment with high-titer Anti- SARS-CoV-2 plasma versus control (SARS-CoV-2 non-immune plasma) in subjects exposed to COVID-19. This will be determined with the presence or occurrence of at least one of the following: Death Requiring mechanical ventilation and/or in ICU non-ICU hospitalization, requiring supplemental oxygen; non-ICU hospitalization, not requiring supplemental oxygen; Not hospitalized, but with clinical and laboratory evidence of COVID-19 infection Not hospitalized, no clinical evidence of COVID-19 infection, but with positive PCR for SARS-CoV-2
Measure: Cumulative incidence of composite outcome of disease severity Time: Day 28Description: Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 0 (baseline).
Measure: Anti-SARS-CoV-2 titers Time: BaselineDescription: Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 1.
Measure: Anti-SARS-CoV-2 titers Time: Day 1Description: Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 3.
Measure: Anti-SARS-CoV-2 titers Time: Day 3Description: Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 7.
Measure: Anti-SARS-CoV-2 titers Time: Day 7Description: Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 14.
Measure: Anti-SARS-CoV-2 titers Time: Day 14Description: Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 90.
Measure: Anti-SARS-CoV-2 titers Time: Day 90Description: Compare the rates of SARS-CoV-2 PCR positivity (RT-PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups at days 0, 7, 14 and 28.
Measure: Rates of SARS-CoV-2 PCR positivity Time: Up to day 28Description: Compare the duration (days) of SARS-CoV-2 PCR positivity (RT-PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups at days 0, 7, 14 and 28.
Measure: Duration of SARS-CoV-2 PCR positivity Time: Up to day 28Description: Compare the peak quantity levels of SARS-CoV-2 RNA amongst the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups at days 0, 7, 14 and 28 days.
Measure: Peak quantity levels of SARS-CoV-2 RNA Time: Up to day 28Description: Cumulative incidence of disease severity between the anti-SARS-CoV-2 convalescent plasma and control groups after individuals develop SARS-CoV-2 infection. Severity of disease will be measured using a clinical event scale of disease severity (evaluated up to Day 28): Death Requiring mechanical ventilation and/or in ICU non-ICU hospitalization, requiring supplemental oxygen; non-ICU hospitalization, not requiring supplemental oxygen; Not hospitalized, but with clinical and laboratory evidence of COVID-19 infection
Measure: Cumulative incidence of disease severity Time: up to Day 28PRIORITY (Pregnancy CoRonavIrus Outcomes RegIsTrY) is a prospective cohort study of pregnant and recently pregnant women who are: either patients under investigation for COVID-19 or a confirmed case of COVID-19. Data from PRIORITY will be used to evaluate the impact of COVID-19 on the clinical course and pregnancy outcomes of pregnant women and women within 6 weeks of pregnancy.
Description: presenting symptoms and testing
Measure: Clinical presentation Time: Baseline to 12 monthsDescription: Clinical outcomes with resolution of illness
Measure: Disease prognosis outcomes Time: Baseline to 12 monthsDescription: Pregnancy outcomes among women infected with COVID-19
Measure: Pregnancy outcomes Time: Baseline to 12 monthsDescription: Obstetric outcomes among women infected with COVID-19
Measure: Obstetric outcomes Time: Baseline to 12 monthsDescription: Neonatal outcomes among infants born to women with COVID-19
Measure: Neonatal outcomes Time: Baseline to 12 monthsDescription: Transmission of COVID-19 from mother to infant
Measure: Modes of transmission of COVID-19 Time: Baseline to 12 monthsThe 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 hoursA phase I/II single-blinded, randomised, multi-centre study to determine efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in UK healthy adult volunteers aged 18-55 years. The vaccine will be administered intramuscularly (IM).
Description: Number of virologically confirmed (PCR positive) symptomatic cases of COVID-19
Measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19: Number of virologically confirmed (PCR positive) symptomatic cases Time: 6 monthsDescription: Occurrence of serious adverse events (SAEs) throughout the study duration
Measure: Assess the safety of the candidate vaccine ChAdOx1 nCoV: Occurrence of serious adverse events (SAEs) Time: 6 monthsDescription: Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination
Measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited local reactogenicity signs and symptoms Time: 7 days following vaccinationDescription: Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination
Measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited systemic reactogenicity signs and symptoms Time: 7 days following vaccinationDescription: Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination
Measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of unsolicited adverse events (AEs) Time: 28 days following vaccinationDescription: Change from baseline for safety laboratory measures (haematology and biochemistry blood results)
Measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV through standard blood tests Time: 6 monthsDescription: Occurrence of disease enhancement episodes
Measure: Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV by measuring the number of disease enhancement episodes Time: 6 monthsDescription: Number of deaths associated with COVID-19
Measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 Time: 6 monthsDescription: Number of hospital admissions associated with COVID-19
Measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 Time: 6 monthsDescription: Number of intensive care unit admissions associated with COVID-19
Measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 Time: 6 monthsDescription: Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study
Measure: Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates Time: 6 monthsDescription: Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein
Measure: Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays Time: 6 monthsDescription: Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates)
Measure: Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 Time: 6 monthsDescription: Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus
Measure: Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through Virus neutralising antibody assays Time: 6 monthsCOVID-19 (Coronavirus Disease-2019) is a life-threatening infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that appeared in December 2019 in the Wuhan district. COVID-19 has since affected more than 150 countries across the world and especially France. The first epidemiological data, mostly from Chinese studies, indicate that diabetes is one of the most common comorbidities, with high blood pressure, in patients with COVID-19. Moreover, the presence of diabetes at admission would be a risk factor for both ICU hospitalization and death. Nevertheless, specific data on people with diabetes and COVID-19 are fragmentary, justifying the achievement of a dedicated prospective observational study. The French nationwide CORONADO study aims to specifically describe the phenotypic characteristics of patients with diabetes admitted to hospital with COVID-19 infection. Particular attention will be devoted to glycemic control at admission (i.e. the level of HbA1c), the diabetic complications, as well as anti-diabetic and antihypertensive therapies. This study will provide answers to caregivers and patients with diabetes regarding the risk factors related to diabetes for COVID-19 prognosis. This pilot study will be used for the development of new studies and for the establishment of recommendations for the cost of care in patients with diabetes and COVID-19.
Description: Prevalence of severe forms among all COVID-19 patients with diabetes
Measure: Assess the prevalence of severe forms among hospitalized patients with diabètes and COVID-19 Time: 1 monthDescription: Use the body weight, type of diabetes, tglycemic control (HbA1C at admission), the comorbidities and complications associated with diabetes and finally the usual therapies.
Measure: describe the clinical and biological characteristics of hospitalized subjects with diabetes and COVID-19 Time: 1 monthDescription: death at 7 days after admission, hospital death and date of death, total length of hospitalization and discharge procedures, serious form requiring the use of artificial ventilation with tracheal intubation and date of use of this treatment, decision to limit
Measure: describe the prognosis of hospitalized subjects with diabetes and COVID-19 Time: 1 monthDescription: care service where the patient is taken care of, insulin therapy (IVSE or multi-injection) and dose of insulin required on D2 and D7
Measure: describe the care management of hospitalized subjects with diabetes and COVID-19 Time: 1 monthThis 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 yearResearchers are trying to assess the treatment potential and safety of anti-SARS-CoV-2 convalescent plasma in patients with acute respiratory symptoms with confirmed COVID-19.
Description: Change in RNA levels of SARS-CoV-2 from nasopharyngeal using RT-PCR (reverse transcriptase polymerase chain reaction) across time.
Measure: RNA in SARS-CoV-2 Time: Days 0, 1, 3, 7, 14, 28, 60 and 90 after transfusionDescription: Total number of subjects to be admitted to the ICU after the anti-SARS-CoV-2 convalescent plasma transfusion.
Measure: ICU Admissions Time: 90 days after transfusionDescription: Total number of subject deaths.
Measure: Hospital Mortality Time: 90 days after transfusionDescription: The total number of days subjects were admitted to the hospital.
Measure: Hospital Length of Stay (LOS) Time: 90 days after transfusionDescription: The type of supplemental oxygen support (e.g. nasal cannula, high flow nasal cannula, noninvasive ventilation, intubation and invasive mechanical ventilation, rescue ventilation) of the anti-SARS-CoV-2 convalescent plasma group across time.
Measure: Type of respiratory support Time: 90 days after transfusion or until hospital discharge (whichever comes first)Description: The total number of days subjects required respiratory support.
Measure: Duration of respiratory support Time: 90 days after transfusion or until hospital discharge (whichever comes first)A new human coronavirus responsible for pneumonia, SARS-CoV-2, emerged in China in December 2019 and has spread rapidly. COVID-19, the disease caused by this virus, has a very polymorphous clinical presentation, which ranges from upper respiratory tract infections to acute respiratory distress syndrome. It may appear serious straightaway or may evolve in two stages, with a worsening 7 to 10 days after the first clinical signs, potentially linked to a cytokine storm and accompanied by a high risk of thrombosis. The global mortality rate of COVID-19 is between 3% and 4%, with severe forms being more frequent among older patients. Management is symptomatic as no antiviral treatment has demonstrated any clinical benefit in this condition. Hydroxychloroquine is a derivative of chloroquine commonly used in some autoimmune diseases, such as systemic lupus erythematosus. It is active in vitro in cellular models of infection by many viruses such as HIV, hepatitis C or SARS-CoV. However, its interest in viral infections in humans has not been demonstrated. Very recently, a preliminary uncontrolled study evaluated the effect of hydroxychloroquine on viral shedding in subjects with COVID-19. Among 20 patients treated with hydroxychloroquine at a dose of 600 mg per day, the percentage of patients with detectable SARS-CoV-2 RNA in the nasopharynx decreased from 100% at inclusion (start of treatment) to 43% six days later. In comparison, 15 of 16 untreated patients had a positive RT-PCR six days after inclusion. Furthermore, hydroxychloroquine has immunomodulating and anti-inflammatory properties, which could theoretically prevent or limit secondary worsening. The research hypothesis is that treatment with hydroxychloroquine improves prognosis and reduces the risk of death or use for invasive ventilation in patients with COVID-19.
Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14 Time: Day 14Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28. Time: Day 28Coronavirus 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 daysCOVID-19 (also known as Coronavirus) originated in the Wuhan China and has since spread to at least 159 countries around the world. It was declared a pandemic by the World health organisation on the 11th of March 2020. The cases in the United Kingdom continue to increase exponentially with up to 5 683 people diagnosed as on the 22nd of March 2020. It is estimated that 1 in 5 people diagnosed will require hospital admission and 1 in 20 intensive care treatment. By developing and improving diagnostic testing, we can accurately diagnose infected cases to triage appropriate treatments, identify individuals for quarantine in order to prevent transmission and obtain information regarding patient's immune systems. At present, the diagnostic test is a highly specific method of genetic amplification called 'Reverse Transcription - Polymerase Chain Reaction' or RT-PCR, which allows detection of very small amounts of genetic mutations caused by the COVID-19 virus. However, this method must be completed in highly specialised facilities, which are few and far between, increasing time to diagnosis (currently 48-72 hours), increasing exposure to non-infected individuals, and overburdening the analysing facilities. The ideal solution is a point of care (POC) test that can give results immediately. This study aims to harness the point of care technology of the SAMBA II device (Diagnostics for the Real World Ltd.), which is a CE-marked device that has been used with success in the identification of Human Immunodeficiency Virus (HIV), by amplifying genetic material without the need to increase and decrease temperatures during the amplification process. In the COVIDx study, 200 patients meeting the Public Health England's (PHE) inpatient definition of having suspected COVID-19 will be approached, consented and a sample from throat and nasal swab (combined) or tracheal fluid taken and tested using the SAMBA II method. A combination of the standard PHE RT-PCR and an additional validated laboratory PCR technique will be used as a control in line with standard clinical practice. Patients will undergo an additional serum tests on existing samples as made available after routine clinical assessments to monitor antibody response. Patients will be followed for clinical outcomes at 28 days post-admission.
Description: Measuring the diagnostic accuracy of the SAMBA II POC-sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) tested against a dual composite reference standard
Measure: SAMBA COVID-19 POC PCR Test Time: 28 daysDescription: Evaluating the participant acceptability of the SAMBA swab intervention using a participant reported discomfort scale
Measure: Patient acceptability Time: 28 daysDescription: Time to positive IgM/IgG test positivity
Measure: Immune Response Positivity Time: 40 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 yearsAs of February 17th, 2020, China has 70635 confirmed cases of coronavirus disease 2019 (COVID-19), including 1772 deaths. Human-to-human spread of virus via respiratory droplets is currently considered to be the main route of transmission. The number of patients increased rapidly but the impact factors of clinical outcomes among hospitalized patients are still unclear.
Description: The primary outcome is the time to negative conversion of coronavirus
Measure: Time to negative conversion of severe acute respiratory syndrome coronavirus 2 Time: 1 monthDescription: The time of hospitalization
Measure: Length of stay in hospital Time: 1 monthDescription: The rate of survival within hospitalization of these patients will be tracked. The rate of survival within hospitalization of these patients will be tracked. The rate of survival within hospitalization of these patients will be tracked. The rate of survival within hospitalization of these patients will be tracked.
Measure: Survival Time: 1 monthDescription: The rate of intubation within hospitalization of these patients will be tracked
Measure: Intubation Time: 1 monthObjective: 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 enrolmentCoronavirus disease 2019 (COVID-19) is a pandemic infection caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because SARS-CoV-2 is known to require the angiotensin-converting enzyme 2 (ACE-2) receptor for uptake into the human body, there have been questions about whether medications that upregulate ACE-2 receptors might increase the risk of infection and subsequent complications. One such group of medications are anti-hypertensives that block the renin-angiotensin system, including both angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB). Both ACEi and ARB are widely used for the treatment of hypertension. Early reports from China and Italy suggest that many of those who die from COVID-19 have a coexisting history of hypertension. Consequently, there have been questions raised as to whether these 2 types of blood pressure medication might increase the risk of death among patients with COVID-19. However, it is well known that the prevalence of hypertension increases linearly with age. Therefore, it is possible that the high prevalence of hypertension and ACEi/ARB use among persons who die from COVID-19 is simply confounded by age (older people are at risk of both a history of hypertension and dying from COVID-19). Whether these commonly prescribed blood pressure medications increase the risk of COVID-19 or not remains unanswered. Statements from professional cardiology societies on both sides of the Atlantic have called for urgent research into this question. Our study aims to randomize patients with primary (essential) hypertension who are already taking ACEi/ARB to either switch to an alternative BP medication or continue with the ACEi/ARB that they have already been prescribed. Adults with compelling indications for ACEi/ARB will not be enrolled.
Description: Time from randomization to the first occurrence of any of the clinical events above
Measure: Number of Covid-19 positive participants who die, require intubation in ICU, or require hospitalization for non-invasive ventilation (NIV) Time: 12 monthsDescription: Time from randomization to the first occurrence of above
Measure: Number of Covid-19 positive participants who die Time: 12 monthsDescription: Time from randomization to the first occurrence of above
Measure: Number of Covid-19 positive participants who require intubation in intensive care unit (ICU) Time: 12 monthsDescription: Time from randomization to the first occurrence of above
Measure: Number of Covid-19 positive participants who require hospitalization for non-invasive ventilation (NIV) Time: 12 monthsDescription: Time from randomization to the first occurrence of above
Measure: Number of SARS-CoV-2 positive participants Time: 12 monthsDescription: Performed in a random sub-sample of the cohort (both study arms)
Measure: 24 hour mean systolic BP (mmHg) on ambulatory BP monitoring Time: 12 monthsDescription: Time from randomization to the first occurrence of above
Measure: All-cause mortality Time: 12 monthsThe purpose of this study is to understand the impact of COVID-19 on patients with cancer through a survey.
Description: We will track the number of participants who fill out the survey for the 12 month duration of the study and the number of participants who participate in the semi-structured telephone interviews.
Measure: Number of participants who fill out the survey and participate in the semi-structured interviews. Time: 12 MonthsThe 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 daysThis is an observational study of patients with COVID-19 designed to specifically address important clinical questions that remain incompletely answered for coronavirus disease 2019.
Convalescent 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)The current health crisis at COVID-19 is forcing us to profoundly rethink our social organizations, especially towards our most fragile seniors. Prohibitions on visits to Nursing Homes and care services, although essential to control the epidemic, are also becoming a major source of social isolation and loneliness for these fragile populations. The only source of residual social ties during a period of confinement remains dematerialised communication via the various existing communication channels (in particular telephone calls or video telephony). As soon as the COVID-19 crisis began and the first visiting restrictions were imposed on patients in the geriatric department of the Angers Univesity Hospital and the Retirement Home / long-term care unit, acute care geriatric unit of Angers offered patients and residents the opportunity to organize communication with their relatives via videophone calls. Initial feedback from the field shows us that, contrary to our intuition, patients and residents are not necessarily asking for communication to the outside world and, when they are, the preferred channel is not necessarily video telephony but often a simple phone call with relatives. Even though the vast majority of projects aimed at setting up communication aids for the elderly now rely on videophonic support, these initial observations in everyday care situations raise questions about the directions taken in this area. Also, the investigators ask themselves the following question: in the absence of a physical meeting, what is the preferred means of communication for elderly people in isolation in hospital or in Retirement Home? This study will make it possible to propose the most appropriate solutions for breaking isolation for the hospitalized or institutionalized geriatric population in order to limit as much as possible the increase in social isolation imposed by restrictions on movement during epidemics.
Description: Choice between videophony, telephony or neither.
Measure: Preferred means of communication for elderly people in isolation, hospitalized in the acute care geriatric unit or residing at St Nicolas nursing home (Angers UH). Time: at baseline (day 0)Description: Aid received or not (by a caregiver) in connecting with the relative.
Measure: proportion of elderly people with loss of functional independence to communicate with their relatives. Time: at baseline (day 0)Description: The satisfaction will be assessed using a non-validated satisfaction questionnaire based on a forced choice Likert scale in 6 points from 1 to 6. Patients will be considered as satisfied if the mean score is over 4 on 6.
Measure: level of satisfaction of patients who have benefited from a telephone call. Time: at baseline (day 0)Description: The satisfaction will be assessed using a non-validated satisfaction questionnaire based on a forced choice Likert scale in 6 points from 1 to 6. Patients will be considered as satisfied if the mean score is over 4 on 6.
Measure: level of satisfaction of patients who have benefited from a videophone call. Time: at baseline (day 0)Description: The satisfaction averages of the two groups wishing to use a means of communication (telephony or videophony) will be compared by a Student t-test.
Measure: satisfaction level of older people according to the means of communication used. Time: at baseline (day 0)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 monthIn December 2019, new coronavirus pneumonia (COVID-19) erupted in Wuhan (Hubei, China) and quickly spread from a single city to the entire country in just 30 days and then attracted worldwide attention. COVID-19 causes a large number of deaths due to its occurrence in many cases. This virus caused a total of 549,461 approved cases and 24,887 deaths worldwide. All the countries of the world take some precautions to prevent the spread of this epidemic disease, which WHO declared it as "pandemic". Staying home and social isolation are at the top of these precautions. For this purpose, in Turkey on March 21, 2020, '65 and older individuals began to apply the curfew to individuals with chronic illnesses. However, not leaving the house and social isolation brings with it the limitation of physical activity. Physical activity (PA) is defined by WHO as any bodily movement produced by the contraction of skeletal muscles that increases energy consumption. Recommended PA levels for the elderly (≥65 years) are similar to adults (18 to 64 years old). At the global level, approximately 45% of people over the age of 60 do not meet the recommended level of PA. Studies investigating the relationship between social isolation and health behavior report consistent findings. Individuals with smaller social networks report less healthy diets, excessive alcohol consumption, and less physical activity. The effects of social isolation are related to physical inactivity, smoking and the possibility of having both health risk behaviors together. The decrease in physical performance is associated with the risk of falling, sarcopenia, fragility, decreased quality of life, emotionalization, comorbidity, early death, and increased health care costs. Practical and innovative interventions are needed to reduce the decline in muscle mass, strength and physical performance in the aging population. When today's conditions are evaluated, technology-supported education programs are effective in increasing the motivation for physical activity. The purpose of this study; to evaluate the physical activity level of individuals over the age of 65 who experience social isolation due to the precautions taken in our country to prevent the spread of the COVID-19 pandemic, and to investigate the effectiveness of home-based telerehabilitation exercises. It is aimed to use an innovative model based on the digitally supported, home-based exercise program.
Description: One of the evaluation parameters created to evaluate the physical activity level of elderly individuals, the factors affecting the activity level, the relationship between physical activity and health profile is the Physical Activity Scale for the Elderly. The minimum score that can be obtained from the scale is 0 and the maximum score is 400. The higher score on the scale indicates a better level of physical activity.
Measure: Physical Activity Scale for the Elderly Time: 2 weeksDescription: Nottingham Health Profile was created in England in 1985 to evaluate the quality of life-related to health. The Nottingham Health Profile is a general quality of life questionnaire that assesses the level of individuals health problems and how they affect their daily life activities.
Measure: Nottingham Health Profile Time: 2 weeksDescription: It was created by Gierveld and Kamphuis in 1985 to evaluate the sense of loneliness in older individuals and was revised in 1999 by Tilburg and Gierveld. It consists of 11 items in total and two subtitles.
Measure: Loneliness Scale for the Elderly Time: 2 weeks.The 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 daysThe mortality rate of the disease caused by the corona virus induced disease (COVID-19) has been estimated to be 3.7% (WHO), which is more than 10-fold higher than the mortality of influenza. Patients with certain risk factors seem to die by an overwhelming reaction of the immune system to the virus, causing a cytokine storm with features of Cytokine-Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS) and resulting in Acute Respiratory Distress Syndrome (ARDS). Several pro-inflammatory cytokines are elevated in the plasma of patients and features of MAS in COVID-19, include elevated levels of ferritin, d-dimer, and low platelets. There is increasing data that cytokine-targeted biological therapies can improve outcomes in CRS or MAS and even in sepsis. Tocilizumab (TCZ), an anti-IL-6R biological therapy, has been approved for the treatment of CRS and is used in patients with MAS. Based on these data, it is hypothesized that TCZ can reduce mortality in patients with severe COVID-19 prone to CRS and ARDS. The overall purpose of this study is to evaluate whether treatment with TCZ reduces the severity and mortality in patients with COVID-19.
Description: Assessed by the 8-point WHO scale
Measure: Illness severity Time: At days 2, 7, 14, 28 after randomisationDescription: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale
Measure: Number of patients with clinical improvement Time: At days 2, 7, 14, 28 after randomisationDescription: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale
Measure: Time to clinical improvement (days) Time: Up to day 28 after randomisationDescription: Events of special interest are defined as secondary infections, acute kidney failure, hepatic, and cardiac failure
Measure: Number of patients with events of special interest Time: Within 28 days after randomisationThis 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 specific objective is to rapidly establish a prospective cohort to characterize the factors related to viral transmission and disease severity in a large healthcare system in healthcare settings and HCW (healthcare worker) households. Investigators propose to address this hypothesis by recruiting and longitudinally following 500 HCW and 250 age- and sex-matched NHCW (Non-healthcare workers) within a large academic health system, Rutgers Biomedical and Health Sciences (RBHS). By intensively following participants over a six-month period and collecting serial biospecimens (nasopharyngeal/throat swabs, blood, and saliva) and questionnaire data at nine time points, investigators can uniquely characterize Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and risk factors for Coronavirus Disease 19 (COVID-19) among health care workers and their families
Description: Prevalence and 95% confidence intervals, using standard epidemiological methods (Aims 1, 2, and 3).
Measure: Prevalence Time: up to 24 weeksDescription: Incidence and 95% confidence intervals, using standard epidemiological methods (Aims 1, 2, and 3).
Measure: Incidence Time: up to 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 studyThe aim of the study is to demonstrate overactivation of Renin Angiotensine System (RAS) in positives COVID-19 patient, especially in those with the most serious clinical forms where the mortality of patients in intensive care is on average 50%. We are expecting two groups: a group of 25 positive COVID 19 patients in intensive care and a group of 25 positive COVID 19 hospitalized patients in conventional hospitalisation. We will measure RAS, serum potassium and collect data on the treatment of these patients (especially antihypertensive therapy) one week apart (at the patient'entry into hospital and 7 days later). This is a preliminary study that could possibly allow the start of a therapeutic trial in order to test the effectiveness of RAS blocker treatments in this condition.
Description: demonstrate overactivity of RAS in patients hospitalised in intensive car secondary to COVID-19 compared to control patients (COVID -19 hospitalised patients without complications ).
Measure: overactivity of the renin / aldosterone system Time: 7 daysWe are aiming to see if participant deterioration due to suspected coronavirus in a designated location (e.g. hotel) can be identified sooner by wearing the sensor. If we can identify sick participants early, participants are more likely to have better outcomes; we believe that the sensor can help us do this. The sensor measures heart rate, respiratory rate and temperature every 2 minutes and this can be reviewed by the clinical team looking after the participants.
Description: Detection of clinical deterioration using wearable sensors resulting in healthcare review (e.g. GP telephone consultation)
Measure: Deterioration resulting in healthcare review Time: 1 yearDescription: Deterioration resulting in hospitalisation
Measure: Hospitalisation Time: 1 yearDescription: GAD-7 questionnaire (repsonses noted on Likert scales)
Measure: Participant anxiety Time: 1 yearDescription: PHQ-9 questionnaire (responses noted on Likert scales)
Measure: Participant depression Time: 1 yearTo develop and validate a machine-learning model based on clinical, laboratory, and radiological characteristics alone or combination of COVID-19 patients to facilitate risk Assessment before and after symptoms and triage (home, hospitalization inward or ICU).
Description: AUC, accuracy, sensitivity, and specificity
Measure: Predictive performance Time: Janunary 1, 2020, to February 13, 2020Since 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 daysThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with a high incidence of acute respiratory distress syndrome (ARDS) and death. Hypertension and cardiovascular disease are risk factors for death in COVID-19. Angiotensin converting enzyme 2 (ACE2), an important component of the renin-angiotensin system, serves as the binding site of SARS-CoV-2 and facilitates host cell entry in the lungs. In experimental models, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been shown to increase ACE2 expression in several organs, potentially promoting viral cell invasion, although these findings are not consistent across studies. Alternatively, ACEIs and ARBs may actually improve mechanisms of host defense or hyperinflammation, ultimately reducing organ injury. Finally, ACEIs and ARBs may have direct renal, pulmonary and cardiac protective benefits in the setting of COVID-19. Therefore, it is unclear if ACEIs and ARBs may be beneficial or harmful in patients with COVID-19. Given the high prevalence of hypertension, cardiovascular and renal disease in the world, the high prevalence of ACEIs or ARBs in these conditions, and the clinical equipoise regarding the continuation vs. discontinuation of ACEIs/ARBs in the setting of COVID, a randomized trial is urgently needed. The aim of this trial is to assess the clinical impact of continuation vs. discontinuation of ACE inhibitors and angiotensin receptor blockers on outcomes in patients hospitalized with COVID-19.
Description: The primary endpoint of the trial will be a global rank score that ranks patient outcomes according to four factors: (1) time to death, (2) the number of days supported by invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), (3) the number of days supported by renal replacement therapy or pressor/inotropic therapy, and (4) a modified sequential Organ Failure Assessment (SOFA) score. The modified SOFA score will include the cardiac, respiratory, renal and coagulation domains of the SOFA score.
Measure: Hierarchical composite endpoint Time: Up to 28 daysDescription: The Area Under the Curve of the modified SOFA (AUC SOFA) from daily measurements, weighted to account for the shorter observation period among patients who die in-hospital.
Measure: AUC SOFA Time: Up to 28 daysDescription: Composite
Measure: Intensive care unit admission or respiratory Failure Requiring Mechanical Ventilation. Time: Up to 28 daysDescription: Hypotension Requiring Vasopressors, inotropes or mechanical hemodynamic support (ventricular assist device or intra-aortic balloon pump).
Measure: Hypotension Requiring Vasopressors, inotropes or mechanical hemodynamic support Time: Up to 28 daysDescription: Number of days in 28-day period feee of invasive or non-invasive mechanical ventilation.
Measure: Number of 28-Day Ventilator-Free Days. Time: Up to 28 daysDescription: Difference between NT-proBNP at the time of randomization and the maximum value
Measure: Maximal change in NT-proBNP from baseline Time: 28 days from enrollmentDescription: as above
Measure: Change in serum creatinine between randomization and discharge (or time of death) Time: Up to 28 daysDescription: defined as Kidney Disease Improving Global Outcomes Stage 2 or higher or initiation of renal replacement therapy
Measure: Acute kidney injury during hospitalization Time: Up to 28 daysDescription: Proteinuria or Hematuria detected on urinalysis
Measure: Proteinuria or Hematuria Time: Up to 28 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 daysThe purpose of this study is to assess the feasibility of delivering anti-SARS-CoV-2 convalescent plasma to hospitalized patients with severe or life-threatening COVID-19. Beyond supportive care, there are currently no proven treatment options for coronavirus disease (COVID-19), the infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Human convalescent plasma is an option for treatment of COVID-19 and could be rapidly available when there are sufficient numbers of people who have recovered and can donate high titer neutralizing immunoglobulin-containing plasma. Hypothesis: Collecting and administering convalescent plasma requires a level of logistical coordination that is not available in all centers. Objective: To establish feasibility for a hospital-based integrated system to collect and administer convalescent plasma to patients with severe or life-threatening COVID-19.
Description: Feasibility will be measured by (number of donors from whom convalescent plasma is harvested/number of interested donors) and number of patients who receive convalescent plasma at day 28.
Measure: Feasibility of performing study pathway consisting of consenting convalescent donors, harvesting convalescent plasma, application for FDA eIND and administering convalescent plasma to the patients Time: 28 days after plasma administrationDescription: Levels of respiratory support will be graded (e.g. room air, high flow oxygen, intubation) to determine the change in type of respiratory support at 28 days.
Measure: Type of respiratory support Time: 28 days after plasma administrationDescription: This will be a continuous outcome defined by the amount of time between plasma administration and cardiac arrest.
Measure: Cardiac arrest Time: 28 days after plasma administrationDescription: This will be a continuous outcome defined by the amount of time between plasma administration and transfer to ICU.
Measure: Transfer to ICU Time: 28 daysDescription: This will be a binary outcome defined by the amount of time between plasma administration and mortality in the ICU.
Measure: ICU mortality Time: 28 daysDescription: This will be a continuous outcome defined by the amount of time between plasma administration and discharge from ICU. This will be treated as a time-to-event.
Measure: ICU length of stay Time: 28 daysDescription: This will be a binary outcome defined by the amount of time between plasma administration and in-hospital mortality.
Measure: Hospital mortality Time: 28 daysDescription: This will be a continuous outcome defined by the amount of time between plasma administration and discharge from hospital.
Measure: Hospital length of stay Time: 28 daysDescription: This will be a continuous outcome defined by the amount of time between plasma administration and the transition from mechanical ventilation to non-invasive respiratory support.
Measure: Ventilator-free days Time: 28 daysDescription: 28-Day Overall Survival is defined as the status of the patient at the end of 28 days, beginning from the time of plasma administration.
Measure: Overall survival (28-day mortality) Time: 28 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 daysThis is a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the safety and efficacy of TJ003234 administered as an intravenous (IV) infusion in subjects with severe COVID-19 under supportive care, and to assess the effect of TJ003234 on the levels of cytokines.
Description: 8-category ordinal scale
Measure: Proportion (%) of subjects experiencing deterioration in clinical status Time: Changes from baseline on Day 14Description: Per CTCAE
Measure: Treatment Emergent Adverse Events Time: Up to 30 days after drug administrationDescription: 8-category ordinal scale
Measure: Proportion (%) of subjects experiencing deterioration in clinical status Time: Changes from baseline on Day 7 and Day 30Description: 8-category ordinal scale: 8, Death; 7, ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT) or pressors; 6, Intubation and mechanical ventilation; 5, non-invasive mechanical ventilation (NIV) or high-flow oxygen; 4,Oxygen by mask or nasal prongs; 3, Hospitalization without oxygen supplementation; 2, Limitation of activities, discharge from hospital; and 1, No limitation of activities, discharge from hospital
Measure: Clinical status Time: On Day 7, Day 14 and Day 30Description: 8-category ordinal scale: 8, Death; 7, ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT) or pressors; 6, Intubation and mechanical ventilation; 5, non-invasive mechanical ventilation (NIV) or high-flow oxygen; 4,Oxygen by mask or nasal prongs; 3, Hospitalization without oxygen supplementation; 2, Limitation of activities, discharge from hospital; and 1, No limitation of activities, discharge from hospital
Measure: Improvement in clinical status Time: On Day 7, Day 14 and Day 30Description: The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. A higher score predicts a worse clinical outcome.
Measure: Sequential Organ Failure Assessment (SOFA) score Time: On Day 7 and Day 14Description: Defined as SpO2≥94% sustained minimum 24 hours
Measure: Length of time to normalization of oxygen saturation Time: Up to 30 days after drug administrationThe 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 daysThere is no predictive tool for patients admitted to the emergency department with a suspicion of Covid-19 that will worsen secondarily and require a heavy lifting. In a context of saturation of the healthcare system by the pandemic at Covid-19,it is essential to identify specific, accessible prognostic markers via minimally invasive sampling with low risk of infection for personnel caregiver, for optimal allocation of resuscitation resources. This study proposes to evaluate the biological markers of routine care known to be associated with resuscitation admission in relation to hospitalization on conventional service for the prediction of worsening of patients admitted to the emergencies for Covid-19.
Description: Secondary aggravation is defined as : a re-hospitalization or aggravation in hospitalization : development or increase in oxygen dependency, hemodynamic failure, and/or respiratory, death
Measure: Rate of secondary aggravation Time: At 30 days of admission to the emergency departmentDescription: the number of leukocytes, lymphocytes, neutrophil polynuclear cells, CRP, fibrinogen, and the D-dimers.
Measure: Change of standart biological parameters Time: Between baseline and at 30 days of admission to the emergency departmentThe 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 research study is to determine if a drug called fluvoxamine can be used early in the course of the COVID-19 infection to prevent more serious complications like shortness of breath. Fluvoxamine is an anti-depressant drug approved by the FDA for the treatment of obsessive-compulsive disorder. The use of fluvoxamine for the treatment of COVID-19 is considered investigational, which means the US Food and Drug Administration has not approved it for this use. This study is fully-remote, which means that there is no face-to-face contact; study materials including study drug will be shipped to participants' houses. Only residents of Missouri and Illinois may participate.
Description: Clinical worsening is defined meeting both of the following: (1) presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, plus (2) decrease in O2 saturation (<92%) on room air and/or supplemental oxygen requirement in order to keep O2 saturation >92%.
Measure: Time to clinical worsening Time: RCT (approximately 15 days)Description: (1) moderate severity of illness as defined by O2 saturation <92% but no supplemental oxygen requirement; (2) O2 saturation plus supplemental oxygen requirement; (3) O2 saturation <92% plus hospitalization (related to dyspnea/hypoxia); (4) the above, plus ventilator support requirement; (5) the above, plus ventilator support for at least 3 days; (6) death.
Measure: clinical deterioration on a Likert-type scale (1-6) Time: RCT (approximately 15 days)Description: (1) requiring supplemental oxygen; (2) requiring hospitalization; (3) requiring ventilator support.
Measure: clinical deterioration measured by number of days Time: RCT (approximately 15 days)Description: Outcomes will be collected daily, with symptomatic data collected approximately twice daily. The most severe symptom at baseline will be the focus.
Measure: Symptomatic severity on a likert scale (0-10 where 0= none and 10=very severe) Time: RCT (approximately 15 days)The 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 purpose of this research is to collect information about the North Carolina community's coronavirus exposures, symptoms, and health care visits due to the virus. Participation in this study will involve completing a daily questionnaire which covers participants coronavirus illness history or symptoms, health care seeking behaviors and treatments, contact with other sick people, and for health care workers, their use of personal protective equipment.
Description: Percent of volunteers who are 2019-nCoV Ab test positive
Measure: Seroprevalence of SARS-CoV-2 infection in the general population of North Carolina Time: baselineDescription: Percent of volunteers who are 2019-nCoV Ab test positive
Measure: Seroprevalence of SARS-CoV-2 infection among health care workers of North Carolina Time: baselineThe 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-monthThe purpose of this study is to collect blood from previously COVID-19 infected persons who have recovered and use it as a treatment for those who are currently sick with a severe or life-threatening COVID-19 infection.
Description: Mortality within 28 days
Measure: Mortality Time: 28 daysDescription: Reduction of Viral Load ]
Measure: Viral Load Time: 7 daysDescription: Change in Serum Antibody Titers
Measure: Serum Antibody Titers Time: 7 daysThis is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with mild-to-moderate symptoms of respiratory illness caused by coronavirus 2019 infection.
Description: Note: The total score per patient ranges from 0 to 12 points. Each symptom is graded from 0 to 3. [0=none, 1=mild, 2=moderate, and 3=severe]. Higher scores mean a worse outcome.
Measure: Clinical Improvement as assessed by change in total symptom score (for fever, myalgia, dyspnea and cough) Time: Day 14Description: This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). Higher scores mean a worse outcome.
Measure: Change from baseline in National Early Warning Score 2 (NEWS2) Time: Days 3, 7, and 14Description: A 7-category ordinal scale of patient health status ranges from: 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. Lower scores mean a worse outcome.
Measure: Change from baseline in the patient's health status on a 7-category ordinal scale Time: Days 3, 7, and 14This 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.
Vitamin D is a secosteroid hormone produced by the skin during Summer exposure to UVB rays. Hypovitaminosis D is common in Winter (October to March) at Northern latitudes above 20 degrees North, and from April to September at Southern latitudes beyond 20 degrees below the equator. In the past, coronaviruses and influenza viruses have exhibited very high seasonality, with outbreaks occurring preferentially during the Winter. The Covid-19 pandemic is indeed more severe above Winter latitudes of 20 degrees, while it remains until now less severe in the Southern hemisphere, with a much lower number of deaths. Preclinical research suggests that the SARS-Cov-2 virus enters cells via the angiotensin converting enzyme 2 (ACE2). Coronavirus viral replication downregulates ACE2, thereby dysregulating the renin-angiotensin system (RAS) and leading to a cytokine storm in the host, causing acute respiratory distress syndrome (ARDS). Research also shows that vitamin D plays a role in balancing RAS and in reducing lung damage. On the contrary, chronic hypovitaminosis D induces pulmonary fibrosis through activation of RAS. Similarly, hypovitaminosis D has been strongly associated in the literature with ARDS, as well as with a pejorative vital prognosis in resuscitation but also in geriatric units, and with various comorbidities associated to deaths during SARS-Cov-2 infections. Conversely, vitamin D supplementation has been reported to increase immunity and to reduce inflammatory responses and the risk of acute respiratory tract infections. High-dose oral vitamin D3 supplementation has been shown to decrease short-term mortality in resuscitation patients with severe hypovitaminosis D (17% absolute risk reduction). It is considered safe to take oral vitamin D supplementation at doses up to 10,000 IU/day for short periods, particularly in older adults, i.e. a population that is mostly affected by hypovitaminosis D and who should receive at least 1,500 IU of vitamin D daily to ensure satisfactory vitamin D status. Vitamin D supplementation is mentioned as a potentially interesting treatment for SARS-Cov-2 infection but on a scientific basis with a low level of evidence until now. We hypothesize that high-dose vitamin D supplementation improves the prognosis of older patients diagnosed with COVID-19 compared to a standard dose of vitamin D.
Description: OSCI ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution between day 0 and day 14 based on the change of the WHO Ordinal Scale for Clinical Improvement (OSCI) for COVID-19 Time: Day 14Description: OSCI ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution between day 0 and day 28 based on the change of the OSCI for COVID-19 Time: Day 28Description: OSCI ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution between day 0 and day 14 based on the change of the OSCI for COVID-19, in patients with severe hypovitaminosis D (25-OHD <25nmol/L) at baseline Time: Day 14Description: OSCI ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution between day 0 and day 28 based on the change of the OSCI for COVID-19, in patients with severe hypovitaminosis D (25-OHD<25nmol/L) at baseline Time: Day 28Description: OSCI ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution between day 0 and day 14 based on the change of the OSCI for COVID-19, depending on serum vitamin D concentration achieved at day 7 (25-OHD<75nmol/L or 25-OHD≥75nmol/L) Time: Day 14Description: OSCI ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution between day 0 and day 28 based on the change of the OSCI for COVID-19, depending on serum vitamin D concentration achieved at day 7 (25-OHD<75nmol/L or 25-OHD≥75nmol/L) Time: Day 28Description: OSCI ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution between day 0 and day 14 based on the change of the OSCI for COVID-19, in patients with severe hypovitaminosis D (25-OHD<25nmol/L) at day 0, depending on serum vitamin D concentration achieved at day 7 (<75nmol/L or ≥75nmol/L) Time: Day 14Description: OSCI ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution between day 0 and day 28 based on the change of the OSCI for COVID-19, in patients with severe hypovitaminosis D (25-OHD<25nmol/L) at day 0, depending on serum vitamin D concentration achieved at day 7 (<75nmol/L or ≥75nmol/L) Time: Day 28The 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 dayBackground: The human disease caused by SARS-CoV-2 is called COVID-19. In most cases, COVID-19 presents as a mild to moderate respiratory illness. But it can also be more severe and even lead to death. There is no vaccine to prevent SARS-CoV-2 infection. There is also no therapy to treat COVID-19. Researchers want to collect plasma from males who have recovered from COVID-19, which may help them develop treatments. Objective: To collect anti-SARS-CoV-2 immune plasma from male volunteers. Eligibility: Males ages 18 to 60 who have a history of COVID-19 like illness, have a history of positive tests for SARS-CoV-2, or are currently participating in a protocol for SARS-CoV-2 plasmapheresis Design: Participants will be screened with a medical history and physical exam Their vital signs (blood pressure, heart rate, temperature, respiration rate) will be taken. Their weight and height will be recorded. They will give a blood sample. They will discuss their history of COVID-19-like illness and date of any testing for SARS-CoV-2. They will be evaluated for their ability to donate plasma. Participants will have 3 to 20 plasma donations. These will occur no less than 7 days apart. Prior to each donation, participants will have a physical exam and complete a donor history questionnaire. They will be asked about any current SARS-CoV-2 infection symptoms. Plasma will be taken through apheresis. For this, blood will be withdrawn through a needle placed in the participant's arm vein. A machine will separate the plasma from the red cells. The red cells will be returned to the participant, either through the same needle or through a second needle in the other arm. Participation will last up to 240 days.
Description: Donors screened and identified and anti-SARS-CoV-2 immune plasma collected
Measure: Identification of eligible donors and collection of anti-SARS-CoV-2 immune plasma Time: Screening, Days 120 or 240CCAP 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 11This is an exploratory study that will be performed on confirmed positive COVID-19 samples to identify the dominant viral genome strain in Egyptians using next generation sequencing (NGS).
Description: Identify the dominant viral genome strain in Egyptians With COVID-19 infection using next generation sequencing (NGS)
Measure: Dominant viral genome strain Time: 9 monthsRetrospective study from November 2019 -Febrauary 2020 on severe respiratory illness to access the presence or absence of COVID-19 in patients samples by real-time PcR
Description: Exploring the presence of COVID-19 in very well preserved oropharyngeal samples since November 2019
Measure: Exploring the presence of COVID-19 Time: 9 monthsCoronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health emergency of major international concern. Currently, no specific drugs or vaccines are available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory monocytes are rapidly activated and then producing a large number of cytokines and inducing an inflammatory storm.Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with COVID-19.
Description: Evaluation of pneumonia improvement
Measure: Changes of oxygenation index (PaO2/FiO2) Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: Proportion of participants with treatment-related adverse events
Measure: Side effects in the BM-MSCs treatment group Time: Baseline through 6 monthsDescription: Improvement of clinical symptoms including duration of fever, respiratory destress, pneumonia, cough, sneezing, diarrhea.
Measure: Clinical outcome Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: days of the patients in hospital
Measure: Hospital stay Time: Baseline through 6 monthsDescription: Evaluation of pneumonia improvement
Measure: CT Scan Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: (deep sputum / pharyngeal swab / nasal swab / anal swab / tear fluid / stomach fluid / feces / blood or alveolar lavage fluid)
Measure: Changes in viral load Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: Immunological status
Measure: Changes of CD4+, CD8+ cells count and concentration of cytokines Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: Marker for efficacy
Measure: Rate of mortality within 28-days Time: From baseline to day 28Description: Markers of Infection
Measure: Changes of C-reactive protein Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.The 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 daysIn December 2019, new coronavirus pneumonia (COVID-19) erupted in Wuhan (Hubei, China) and quickly spread from a single city to the entire country. It did not take long for this epidemic to spread to the world. After that, World Health Organization declared this epidemic disease as a pandemic. As of now, the number of coronavirus deaths increased to 108,281 worldwide. Total number of cases approached 1,800,000 according to the latest information. While the number of healed patients was highest in China, 77,525 people with COVID-19 recovered. COVID-19 is a highly contagious respiratory infectious disease that can cause respiratory, physical and psychological dysfunction in patients. Respiratory rehabilitation reduces the patient's symptoms of dyspnea, relieves anxiety and depression, reduces the patient's need to apply to the hospital, increases functional capacity and improves the patient's quality of life. Respiratory rehabilitation, according to the feedback from China, is very important for patients in the clinical treatment and recovery process after treatment. Rehabilitation of people with mild disease after discharge is mainly based on improving physical fitness and psychological adaptation. It is also aimed to gradually restore the individual's ability to the activity before the disease and return to the community as soon as possible. Individuals with COVID-19 who have respiratory and / or limb dysfunction and chronic disease after discharge should receive respiratory rehabilitation therapy. According to the current findings of the patients discharged from severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS) and the clinical experience of patients with Acute Respiratory Distress Syndrome (ARDS) patients who recovered after discharge, COVID-19 patients may have physical fitness, dyspnea after activity, and muscle atrophy. (Including respiratory muscles and trunk muscles) It is recommended to use respiratory videos and booklets as the main method for respiratory rehabilitation in isolated patients at home. Telerehabilitation method is also a different recommendation option for rehabilitation. The purpose of this study is to investigate the effects of exercises performed by telerehabilitation in patients diagnosed with COVID-19 followed at home. It is aimed to use an innovative model based on the digitally supported, home-based exercise program.
Description: Visual Analogue Scale (VAS) is a horizontal line, 100 mm in length, and anchored by word descriptors at each end. The VAS dyspnea score uses "no shortness of breath at all" and "maximum shortness of breath" . The patient marks on the line the point that they feel represents the perception of their current state. The distance (mm) between the beginning of the horizontal line and this mark represents the degree of dyspnea perception
Measure: Visual Analogue Scale Time: 2 weeksDescription: This scale used was a modified Borg scale of perceived exertion adapted to be appropriate for measuring fatigue. This consisted of a vertical scale labelled 0-10, with corresponding verbal expressions of progressively increasing perceived sensation intensity. (0 = no fatigue , 10 = maximal fatigue)
Measure: Modified Borg Scale Time: 2 weeksDescription: Leicester Cough Questionnaire (LCQ) is an English-born self-reporting quality of life measure of chronic cough. It consists of 19 items with a 7 point likert response scale (range from 1 to 7). Each item is developed to assess symptoms during cough and impact of cough on three main domains: physical, psychological and social. Scores are calculated as a mean of each domain and the total score is calculated by adding every domain score. It generally takes about 5 minutes to be completed and it is designed for adults
Measure: Leicester Cough Questionnaire Time: 2 weeksDescription: The Timed Up and Go test (TUG) is a simple test used to assess a person's mobility and requires both static and dynamic balance. It uses the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down. During the test, the person is expected to wear their regular footwear and use any mobility aids that they would normally require
Measure: Timed Up and Go Time: 2 weeksDescription: The 30-s Chair Stand Test consists of standing up and sitting down from a chair as many times as possible within 30 seconds. A standard chair without backrest, but with armrests is used. Initially, the person is seated on the chair with his backs upright. They are told to look forward with their arms folded in their chest and rise at their preferred speed after the command "1, 2, 3, go". All trials must be carried out using the same chair and similar environmental conditions.
Measure: 30 Second Chair Stand Test Time: 2 weeksDescription: The Beck Depression Inventory (BDI) is a 21-item, self-rated scale that evaluates key symptoms of depression. Individual scale items are scored on a 4-point continuum (0=least, 3=most), with a total summed score range of 0-63. Higher scores indicate greater depressive severity. Two subscales include a cognitive-affective subscale and a somatic-performance subscale
Measure: The Beck Depression Inventory Time: 2 weeksDescription: The Beck Anxiety Inventory (BAI) is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in children and adults.The questions used in this measure ask about common symptoms of anxiety . It is designed for individuals who are of 17 years of age or older and takes 5 to 10 minutes to complete. Several studies have found the Beck Anxiety Inventory to be an accurate measure of anxiety symptoms in children and adults
Measure: The Beck Anxiety Inventory Time: 2 weeksIn December 2019, new coronavirus pneumonia (COVID-19) broke out in Wuhan (Hubei, China), and it spread rapidly from one city to the whole country in just 30 days, and then worldwide cases began to appear. All the countries of the world take some precautions to prevent the spread of this epidemic disease, which WHO declared as "pandemic". Apart from compulsory situations, non-home and social isolation are the primary measures. However, not leaving the house and social isolation brings with it the restriction of physical activity. According to World Health Organization (WHO), in order to obtain health benefits, adult individuals between the ages of 18-64 should perform at least 150 minutes of physical activity per week (30 minutes a day for 5 days a week) or intensive physical activity for at least 75 minutes a week. For additional health benefits, adults should increase their moderate-intensity physical activities to at least 300 minutes a week or equivalent. Physical activity; It is directly related to the prevention of chronic diseases, increasing fitness, strengthening the muscles and increasing the quality of life. It is reported that one of the ten main risk factors in terms of mortality in the world is insufficient physical activity. The effects of social isolation are related to physical inactivity, smoking and the possibility of having both health risk behaviors together. Practical and innovative interventions are needed to reduce physical performance and decrease in muscle mass, strength and physical performance in the aging population. Considering today's conditions and current COVID-19 Pandemic, technology-supported exercise programs are effective in increasing the motivation for physical activity. The purpose of this study; In order to prevent the spread of the COVID-19 pandemic, social isolation, which is one of the measures taken in our country, is to evaluate the physical activity level of adults and to investigate the effectiveness of home exercises. It is aimed to use a model based on the video supported by a home-based exercise program.
Description: The International Physical Activity Questionnaire -Short Form (IPAQ-SF) measures the frequency and duration of moderate physical activity, vigorous physical activity, walking, and sedentary behavior using 7 questions and is considered more suitable for population surveillance and large-scale studies compared with the long form . The IPAQ-SF was validated for adults.According to the score obtained, the physical activity levels of individuals are determined. It indicates lower physical activity level below 600 Metabolic Equivalent Threshold (MET)-min per week, medium physical activity level between 600-3000 Metabolic Equivalent Threshold (MET)-min per week and high physical activity level between 600-3000 Metabolic Equivalent Threshold (MET)-min per week.
Measure: International Physical Activity Questionnaire - Short Form Time: 2 weeksDescription: Nottingham Health Profile was created in England in 1985 to evaluate the quality of life-related to health. The Nottingham Health Profile is a general quality of life questionnaire that assesses the level of individuals health problems and how they affect their daily life activities.
Measure: Nottingham Health Profile Time: 2 weeksDescription: It is among the most used scales to measure depression all over the world. It consists of 21 questions in total. Each item gets points between 0-3. 11-17 points indicate mild depression, 18-29 points indicate moderate depression, and 30-63 points indicate severe depression.
Measure: Beck Depression Inventory Time: 2 weeks.Description: It is used to evaluate the anxiety symptoms experienced by individuals due to social isolation. It consists of 21 items and is scored between 0-3. It indicates low anxiety of 0-21 points, moderate anxiety of 22-35 points and high anxiety of 36 points and above.
Measure: Beck Anxiety Inventory Time: 2 weeksDescription: It is a scale that provides information about sleep quality and type and severity of sleep disorder in the last month. The sleep quality of the person on this scale; sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, sleep medication use and daytime dysfunction. Each question is given a score of 0-3. High scores reflect poor sleep quality. If the total score obtained from the scale is less than 5, it is defined as "Good sleep quality" and 5 and above is defined as "Bad sleep quality".
Measure: Pittsburgh Sleep Quality Index Time: 2 weeksDescription: Used for mobility assessment. The test begins while the person is sitting in the chair. The person is asked to get up from the chair, walk 3 meters, come back and sit on the chair again, and the time is recorded. If an elderly person completes the test for more than 12 seconds, there is a risk of falling.
Measure: Timed Get Up and Go Test Time: 2 weeksDescription: Flamingo Balance Test will be used to evaluate the static balance of the individuals who will participate in the study. This test is done on one foot. While individuals are in balance with one foot, time begins and tries to stay in balance for 1 minute. The time is stopped when the balance is disturbed. When the time is completed, each individual attempt to balance is counted and this number is recorded as the individual's score at the end of the test. If the individual tries to balance 15 times in the first 30 seconds, the test is stopped and zero points are given.
Measure: Flamingo Balance Test Time: 2 weeksThe purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injection in subjects with severe or critical COVID-19 disease.
Description: Day 0 refers to the data of randomization/first treatment.
Measure: All-cause mortality at Day 28 Time: Day 28Description: Day 0 refers to the data of randomization/first treatment.
Measure: All-cause mortality at Day 14 Time: Day 14Description: A 7-category ordinal scale of patient health status ranges from: 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: Change in clinical status of subject at Day 14 (on a 7 point ordinal scale) Time: Day 14Description: A 7-category ordinal scale of patient health status ranges from: 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: Change in clinical status of subject at Day 28 (on a 7 point ordinal scale) Time: Day 28Description: The SOFA score assessment will be based on PaO2/FiO2, platelets, Glasgow coma scale (GCS), bilirubin, Mean arterial pressure OR administration of vasoactive agents required, and Serum creatinine
Measure: Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 14. Time: Day 14To 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 daysA prospective investigation and screening of all HCWs working in all governmental university hospitals and the affiliated COVID-19 quarantine hospitals using an online survey and laboratory testing using rapid serological tests and PCR. To date, the Ministry of Higher Education has dedicated quarantine hospitals at the following governmental universities: Ain Shams, Cairo, Helwan, Alexandria, Mansoura, Assiut, Minia. This list may be expanded in the future. The project will be pilot tested in Ain Shams University, then extended to other universities subsequently. For risk categorization of HCWs exposed to COVID-19 virus and assessment of infection control needs, an online survey questionnaire will be administered to all HCWs in the governmental university hospitals involved in emergency and intensive care and in the provision of care for COVID-19 patients in the affiliated COVID-19 quarantine hospitals. For confirmation of infection and determination of the secondary infection rate, paired serological samples at baseline and after exposure will be collected. For measuring the validity of the available rapid serological tests, a respiratory sample will be taken for viral detection by RT-PCR. A real-time interactive map using geographical information system programming will be developed to flag hotspots for HCWs' risk and infection control needs that originated from the online survey risk categorization in governmental university and COVID-19 quarantine hospitals. Policy and decision makers will use the map to manage emergency healthcare resource mobilization based on HCWs' risk and infection control needs.
Description: To determine the risk categorization of HCWs for exposure to a COVID-19 patient using an online survey in governmental university and COVID-19 quarantine hospitals
Measure: Risk categorization of healthcare workers Time: 9 monthsDescription: To estimate the COVID-19 infection rate among HCWs in governmental university and quarantine hospitals.
Measure: COVID-19 infection rate among health care workers Time: 9 monthsDescription: To determine the risk factors for COVID-19 among health care workers in governmental university and quarantine hospitals.
Measure: Risk factors for COVID-19 among health care workers Time: 9 monthsDescription: To evaluate adherence of HCWs to infection prevention and control measures using an online survey in governmental university and COVID-19 quarantine hospitals.
Measure: Adherence of health care workers to infection prevention Time: 9 monthsDescription: To determine the validity (sensitivity and specificity) of the available rapid serological test for detecting COVID-19 virus infection among HCWs in governmental university and COVID-19 quarantine hospitals.
Measure: Validity of the available rapid serological test for detecting COVID-19 virus infection Time: 9 monthsDescription: To characterize the risk factors, clinical spectrum, duration and severity of COVID-19 infections among HCWs in governmental university and quarantine hospitals.
Measure: Clinical spectrum of COVID-19 Time: 9 monthsDescription: To evaluate the effectiveness of infection prevention and control measures programs at health facility level using an online survey tool in governmental university and COVID-19 quarantine hospitals
Measure: Effectiveness of infection prevention in the health care facility Time: 9 monthsDescription: To determine the emergency infection prevention and control needs among HCWs using an online survey tool in governmental university and COVID-19 quarantine hospitals
Measure: Emergency infection prevention and control needs Time: 9 monthsDescription: To determine the isolation rate among HCWs and the need for emergency HCW replacement in governmental university and COVID-19 quarantine hospitals.
Measure: Isolation rate and emergency health care worker replacement needs Time: 9 monthsDescription: To determine the serologic response for HCWs with symptomatic and possibly asymptomatic COVID-19 virus infection in governmental university and COVID-19 quarantine hospitals.
Measure: Rate of seroconversion Time: 9 monthsSARS-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 daysProspective interventional study, single arm of purified convalescent plasma transfusion as an add on therapy for the standard of care treatment (national guideline) (Oseltamivir (75mg/12 hours for 5-10 days) and hydroxychroquine (400mg twice in first day, 200 twice for 4-9 days) ± Azithromycin 500mg daily for 5 days
Description: Two successive negative COVID-19 PCR analysis tests 72 hours apart
Measure: viral COVID-19 clearance Time: 14 daysDescription: The percentage of decrease of radiological abnormalities at day 14
Measure: Decrease of radiological abnormalities Time: 14 daysDescription: Clinical improvement in form of normal body temperature for 48 hours
Measure: Clinical improvement Time: 14 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 yearRandomized controlled interventional trial (Clinical Trial) phase 3 to assess the safety and efficacy of favipiravir versus the standard care therapy in the treatment of patients with COVID-19.
Description: Two successive negative COVID-19 PCR analysis tests 48-72 hours apart
Measure: Viral clearance Time: 14 daysDescription: Normal body temperature for 48 hours
Measure: Clinical improvement Time: 14 daysDescription: Improvement of radiological abnormalities at day 14
Measure: Radiological Improvement Time: 14 daysThe 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 weeksGiven the high prevalence of COVID19 illness (both SARS-CoV-2 RT-PCR confirmed and highly suspect cases) among healthcare workers (HCW) within the Montefiore Health System (MHS), hydroxychloroquine (HCQ) will be prescribed to healthcare workers who are at the highest risk for severe COVID19 illness.
Description: Time that it takes for symptoms to be resolved in those who were treated vs untreated
Measure: Time to resolution of symptoms Time: up to 4 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 daysPhase III Placebo-controlled adaptive multi-centre randomized controlled trial Interventional (Clinical Trial). The study will include nine hundred healthcare workers in the isolation hospitals for COVID-19 cases; they will be randomly assigned to receive either BCG vaccine or normal saline.
Description: Estimate the incidence of confirmed COVID-19 among the healthcare workers in isolation hospitals
Measure: incidence of confirmed COVID-19 Time: 9 monthsDescription: Evaluate the effectiveness of BCG vaccine in protecting the healthcare workers in isolation hospitals against the risk of COVID-19 infection by detecting any positive cases among vaccinated healthscare workers
Measure: Effectiveness of BCG vaccine Time: 9 monthsThe primary objective of this study is to assess whether the use of lenzilumab in addition to current standard of care (SOC) can alleviate the immune-mediated cytokine release syndrome (CRS) and prevent progression to respiratory failure and/or death in high risk patients with COVID-19 pneumonia.
Description: Acute respiratory distress syndrome defined as new or worsening respiratory symptoms with PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 315, chest imaging (radiograph, CT scan, or lung ultrasound) revealing bilateral opacities and pulmonary infiltrates not fully explained by fluid overload or cardiac failure
Measure: Incidence of acute respiratory distress syndrome (ARDS) Time: Up to 28 daysDescription: Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measure: Percentage of Participants Experiencing Adverse Events Time: Up to 60 daysDescription: Using the NCI CTCAE version 5.0
Measure: Percentage of Participants Experiencing Serious Adverse Events