Name (Synonyms) | Correlation | |
---|---|---|
drug505 | Hydroxychloroquine Wiki | 0.28 |
drug850 | Placebo Wiki | 0.27 |
drug865 | Placebo oral tablet Wiki | 0.15 |
drug431 | Favipiravir Wiki | 0.14 |
drug60 | Anakinra Wiki | 0.14 |
drug522 | Hydroxychloroquine Sulfate Wiki | 0.13 |
drug1255 | Zinc Wiki | 0.12 |
drug587 | Interferon Beta-1B Wiki | 0.12 |
drug650 | Losartan Wiki | 0.11 |
drug898 | Presatovir Wiki | 0.11 |
drug526 | Hydroxychloroquine Sulfate 200 MG Wiki | 0.10 |
drug1403 | standard therapy Wiki | 0.10 |
drug510 | Hydroxychloroquine + azithromycin Wiki | 0.10 |
drug820 | PUL-042 Inhalation Solution Wiki | 0.10 |
drug467 | HB-adMSCs Wiki | 0.10 |
drug508 | Hydroxychloroquine + Azithromycin Wiki | 0.10 |
drug828 | Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances Wiki | 0.10 |
drug1230 | Vitamin C Wiki | 0.09 |
drug506 | Hydroxychloroquine (HCQ) Wiki | 0.08 |
drug1291 | convalescent plasma Wiki | 0.08 |
drug1287 | collection of biological samples Wiki | 0.07 |
drug1256 | Zinc (Placebo) Wiki | 0.07 |
drug730 | NO-Immunosuppressive Wiki | 0.07 |
drug1342 | methylprednisolone therapy Wiki | 0.07 |
drug942 | Ranitidine Wiki | 0.07 |
drug56 | Alvelestat (MPH996) Plus Aerosolized 13 cis retinoic acid Wiki | 0.07 |
drug248 | Carrimycin Wiki | 0.07 |
drug926 | Questionnaire with precaution information Wiki | 0.07 |
drug1279 | blood samples Wiki | 0.07 |
drug835 | Peginterferon lambda alfa-1a subcutaneous injection Wiki | 0.07 |
drug84 | Ascorbic Acid and Zinc Gluconate Wiki | 0.07 |
drug1234 | VivaDiag™ COVID-19 lgM/IgG Rapid Test Wiki | 0.07 |
drug311 | Convalescent Plasma 1 Unit Wiki | 0.07 |
drug342 | Dapagliflozin Wiki | 0.07 |
drug699 | Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF) Wiki | 0.07 |
drug273 | Clarithromycin Wiki | 0.07 |
drug477 | Halo Oral Spray Wiki | 0.07 |
drug616 | JNJ-53718678 Wiki | 0.07 |
drug783 | Observational Study Wiki | 0.07 |
drug1237 | WHO recommendations (waiting condition) Wiki | 0.07 |
drug910 | Psycho-Social Questionnaire Wiki | 0.07 |
drug916 | Pyridostigmine Bromide Wiki | 0.07 |
drug427 | Extra blood sample Wiki | 0.07 |
drug1350 | nasal pharyngeal (NP) swab samples Wiki | 0.07 |
drug904 | Prone position ventilation Wiki | 0.07 |
drug944 | Rapid molecular test Wiki | 0.07 |
drug476 | HOME-CoV rule implementation Wiki | 0.07 |
drug1259 | Zithromax Oral Product Wiki | 0.07 |
drug1240 | Web Based Survey Wiki | 0.07 |
drug152 | BioMedomics COVID-19 IgM-IgG Rapid Test Wiki | 0.07 |
drug281 | Clinical examination Wiki | 0.07 |
drug1090 | Sterile Normal Saline for Intravenous Use Wiki | 0.07 |
drug341 | Danoprevir+Ritonavir Wiki | 0.07 |
drug967 | Rintatolimod Wiki | 0.07 |
drug57 | Ambrisentan Wiki | 0.07 |
drug486 | Hidroxicloroquina Wiki | 0.07 |
drug1270 | azithromycin Wiki | 0.07 |
drug1232 | Vitamin D3 Wiki | 0.07 |
drug655 | Low nitrite/NDMA meals Wiki | 0.07 |
drug1080 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation Wiki | 0.07 |
drug423 | Experimental: Questionnaire without precaution information Wiki | 0.07 |
drug690 | Melatonin 2mg Wiki | 0.07 |
drug162 | Biomarkers expression Wiki | 0.07 |
drug1252 | Zanubrutinib Wiki | 0.07 |
drug648 | Lopinavir/ritonavir 400 mg/100 mg Wiki | 0.07 |
drug908 | Prototype swab Wiki | 0.07 |
drug81 | ArtemiC Wiki | 0.07 |
drug676 | Mannitol Wiki | 0.07 |
drug872 | Placebos Wiki | 0.07 |
drug1005 | Saline Nasal Irrigation Wiki | 0.07 |
drug360 | Desferal 500 MG Injection Wiki | 0.07 |
drug760 | Nivolumab Injection Wiki | 0.07 |
drug472 | HCQ + Placebo Wiki | 0.07 |
drug1078 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation Wiki | 0.07 |
drug83 | Ascorbic Acid Wiki | 0.07 |
drug285 | Cohort Wiki | 0.07 |
drug861 | Placebo of Hydroxychloroquine Wiki | 0.07 |
drug805 | Outpatient MRI Wiki | 0.07 |
drug444 | Fluvoxamine Wiki | 0.07 |
drug470 | HCQ & AZ vs HCQ+SIR Wiki | 0.07 |
drug700 | Mid-dose chloroquine Wiki | 0.07 |
drug3 | - Synthetic anti-malarial drugs Wiki | 0.07 |
drug157 | Biological samples specific to research Wiki | 0.07 |
drug536 | Hydroxychloroquine and azithromycin treatment Wiki | 0.07 |
drug520 | Hydroxychloroquine Pre-Exposure Prophylaxis Wiki | 0.07 |
drug1183 | Treatment with Dexmedetomidine Wiki | 0.07 |
drug601 | Interview Wiki | 0.07 |
drug843 | Physical Exam Wiki | 0.07 |
drug1153 | There is no intervention in this study Wiki | 0.07 |
drug388 | EDP1815 Wiki | 0.07 |
drug377 | Dornase Alfa Wiki | 0.07 |
drug870 | Placebo: Emtricitabine/tenofovir disoproxil Placebo Wiki | 0.07 |
drug275 | Clazakizumab 12.5 mg Wiki | 0.07 |
drug803 | Others(No intervention) Wiki | 0.07 |
drug530 | Hydroxychloroquine Sulfate 600 mg once a day Wiki | 0.07 |
drug644 | Lopinavir and ritonavir Wiki | 0.07 |
drug1166 | To assess for development of IgG antibodies against SARS-CoV2 Wiki | 0.07 |
drug1323 | identify SARS-CoV-2 infection by serology Wiki | 0.07 |
drug543 | Hydroxychloroquine sulfate &Azithromycin Wiki | 0.07 |
drug965 | Ribavirin Wiki | 0.07 |
drug575 | Indomethacin Wiki | 0.07 |
drug553 | Hyperimmune plasma Wiki | 0.07 |
drug1233 | Vitamins Wiki | 0.07 |
drug1109 | Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors Wiki | 0.07 |
drug1074 | Standard screening strategy Wiki | 0.07 |
drug380 | Drug Isotretinoin (13 cis retinoic acid ) capsules+standard treatment Wiki | 0.07 |
drug127 | BM-Allo.MSC Wiki | 0.07 |
drug1383 | quetionnary Wiki | 0.07 |
drug471 | HCQ + Intravenous Famotidine Wiki | 0.07 |
drug680 | Matched Placebo Hydroxychloroquine Wiki | 0.07 |
drug909 | Psychiatric counseling Wiki | 0.07 |
drug312 | Convalescent Plasma 2 Units Wiki | 0.07 |
drug949 | Recombinant Interferon Alfa-2b Wiki | 0.07 |
drug337 | DAS181 COVID-19 Wiki | 0.07 |
drug938 | Radiation therapy Wiki | 0.07 |
drug1147 | The standard Macintosh laryngoscope Wiki | 0.07 |
drug329 | Covid-19 + patients Wiki | 0.07 |
drug123 | BCG-Denmark Wiki | 0.07 |
drug863 | Placebo oral Wiki | 0.07 |
drug469 | HCQ & AZ Wiki | 0.07 |
drug1174 | Tradipitant Wiki | 0.07 |
drug478 | Halo Placebo Wiki | 0.07 |
drug852 | Placebo + Placebo Wiki | 0.07 |
drug8 | 18F-αvβ6-BP Wiki | 0.07 |
drug1028 | Serum SARs COV 2 IGg screening in health care workers Wiki | 0.07 |
drug1375 | plasma hyperimmune Wiki | 0.07 |
drug1400 | standard operating procedures Wiki | 0.07 |
drug1394 | serum inflammatory biomarkers Wiki | 0.07 |
drug1245 | Whole Exome Sequencing Wiki | 0.07 |
drug1145 | The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care: Wiki | 0.07 |
drug1386 | remdesivir Wiki | 0.07 |
drug124 | BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki | 0.07 |
drug1269 | artus Influenza A/B RT-PCR Test Wiki | 0.07 |
drug395 | Education sessions Wiki | 0.07 |
drug862 | Placebo of LPV/r Tablets Wiki | 0.07 |
drug325 | CoronaCideTM COVID-19 IgM/IgG Rapid Test and Premier Biotech COVID-19 IgM/IgG Rapid Test Wiki | 0.07 |
drug1092 | Stool collection or fecal swab Wiki | 0.07 |
drug507 | Hydroxychloroquine (placebo) Wiki | 0.07 |
drug1317 | hydroxychloroquine placebo Wiki | 0.07 |
drug746 | New screening strategy Wiki | 0.07 |
drug276 | Clazakizumab 25 mg Wiki | 0.07 |
drug541 | Hydroxychloroquine plus standard preventive measures Wiki | 0.07 |
drug493 | High-dose chloroquine Wiki | 0.07 |
drug487 | Hidroxicloroquina + Azitromicina o Lopinavir/ritonavir + Interferon β-1b + Hidroxicloroquina Wiki | 0.07 |
drug540 | Hydroxychloroquine plus Nitazoxanide Wiki | 0.07 |
drug1392 | serological test Wiki | 0.07 |
drug396 | Eicosapentaenoic acid gastro-resistant capsules Wiki | 0.07 |
drug265 | Chloroquine analog (GNS651) Wiki | 0.07 |
drug1418 | vaccine BCG Wiki | 0.07 |
drug581 | Inhaled nitric oxide gas Wiki | 0.07 |
drug466 | HB-adMSC Wiki | 0.07 |
drug13 | 1: discontinuation of RAS blocker therapy Wiki | 0.07 |
drug1328 | laboratory biomarkers Wiki | 0.07 |
drug307 | Control swab Wiki | 0.07 |
drug455 | Gargle/Mouthwash Wiki | 0.07 |
drug432 | Favipiravir + Standard of Care Wiki | 0.07 |
drug961 | ResCure™ Wiki | 0.07 |
drug539 | Hydroxychloroquine in combination of Azithromycin Wiki | 0.07 |
drug579 | Inhaled beclomethasone Wiki | 0.07 |
drug18 | 2: Usual practice + SYMBICORT RAPIHALER Wiki | 0.07 |
drug451 | GO2 PEEP MOUTHPIECE Wiki | 0.07 |
drug983 | SARILUMAB Wiki | 0.07 |
drug413 | Equipment with smartwatch throughout hospital stay on the general ward Wiki | 0.07 |
drug1319 | hyper immunoglobulins containing anti-Corona VS2 immunoglobulin Wiki | 0.07 |
drug748 | Next generation Sequencing (NGS) analysis Wiki | 0.07 |
drug260 | Chinese Herbal Medicine Wiki | 0.07 |
drug402 | Elisa-test for IgM and IgG to SARS-CoV-2 Wiki | 0.07 |
drug559 | IV Deployment Of cSVF In Sterile Normal Saline IV Solution Wiki | 0.07 |
drug1330 | lopinavir/ritonavir Wiki | 0.07 |
drug866 | Placebo plus standard preventive measures Wiki | 0.07 |
drug399 | Electric pad for human external pain therapy Wiki | 0.07 |
drug369 | Dialyzable Leukocyte Extract Wiki | 0.07 |
drug1416 | trimethoprim/sulfamethoxazole Wiki | 0.07 |
drug384 | Duvelisib Wiki | 0.07 |
drug588 | Interferon beta 1a Wiki | 0.07 |
drug209 | COVID-19 IgM/IgG Rapid Testing, mobile device image capture and telemedicine support Wiki | 0.07 |
drug434 | Favipiravir and Hydroxychloroquine Wiki | 0.07 |
drug1079 | Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection Wiki | 0.07 |
drug1294 | conventional management of patients Wiki | 0.07 |
drug465 | Guided online support program Wiki | 0.07 |
drug611 | Isotretinoin(Aerosolized 13 cis retinoic acid) +standard treatment Wiki | 0.07 |
drug1235 | Volatile Organic Compounds analysis Wiki | 0.07 |
drug564 | IgM and IgG diagnostic kits to SARS-CoV-2 Wiki | 0.07 |
drug177 | Blood sample for whole genome sequencing Wiki | 0.07 |
drug1013 | Sarilumab Prefilled Syringe Wiki | 0.07 |
drug1274 | bidirectional oxygenation mouthpiece Wiki | 0.07 |
drug643 | Lopinavir and Ritonavir Tablets Wiki | 0.07 |
drug519 | Hydroxychloroquine Oral Product Wiki | 0.07 |
drug254 | Centricyte 1000 Wiki | 0.07 |
drug496 | Huaier Granule Wiki | 0.07 |
drug1292 | convalescent plasma application to SARS-CoV-2 infected patients Wiki | 0.07 |
drug1261 | a specifically designed self-administered questionnaire Wiki | 0.07 |
drug899 | Presatovir placebo Wiki | 0.07 |
drug632 | Liberase Enzyme (Roche) Wiki | 0.07 |
drug12 | 1: Usual practice Wiki | 0.07 |
drug1105 | Surgical facial mask Wiki | 0.07 |
drug1275 | biological samples collection Wiki | 0.07 |
drug969 | Risk of MERS infection Wiki | 0.07 |
drug1201 | Ulinastatin Wiki | 0.07 |
drug1262 | additional blood tubes Wiki | 0.07 |
drug147 | Best Practice Wiki | 0.07 |
drug529 | Hydroxychloroquine Sulfate 400 mg twice a day Wiki | 0.07 |
drug1159 | Thrombin Generation Assay (TGA) Wiki | 0.07 |
drug1316 | hydroxychloroquine in combination with camostat mesylate Wiki | 0.07 |
drug498 | Human biological samples Wiki | 0.07 |
drug871 | Placebo: Hydroxychloroquine Wiki | 0.07 |
drug523 | Hydroxychloroquine Sulfate (HCQ) Wiki | 0.07 |
drug518 | Hydroxychloroquine Only Product in Oral Dose Form Wiki | 0.07 |
drug1030 | Serum testing Wiki | 0.07 |
drug1393 | serum chemistry analysis Wiki | 0.07 |
drug1318 | hydroxychloroquine sulfate 200 MG Wiki | 0.07 |
drug740 | Naso pharyngeal swab Wiki | 0.07 |
drug1257 | Zinc Gluconate Wiki | 0.07 |
drug235 | CYNK-001 Wiki | 0.07 |
drug245 | Caption AI Wiki | 0.07 |
drug414 | Ergocalciferol Wiki | 0.07 |
drug421 | Exercise brochure Wiki | 0.07 |
drug422 | Experimental drug Wiki | 0.07 |
drug583 | Injection and infusion of LV-SMENP-DC vaccine and antigen-specific CTLs Wiki | 0.07 |
drug923 | Questionnaire Wiki | 0.07 |
drug1231 | Vitamin D Wiki | 0.07 |
drug263 | Chloroquine Diphosphate Wiki | 0.07 |
drug367 | Diagnosis of SARS-Cov2 by RT-PCR and : IgG, Ig M derologies in the amniotoc fluid, the blood cord and the placenta Wiki | 0.07 |
drug223 | COVID-19 positive via testing Wiki | 0.07 |
drug1217 | VRC-SRSDNA015-00-VP Wiki | 0.07 |
drug19 | 2: continuation of RAS blocker therapy Wiki | 0.07 |
drug1334 | lung ultrasound (LUS) Wiki | 0.07 |
drug1371 | phone call Wiki | 0.07 |
drug845 | Physical exercise Wiki | 0.07 |
drug338 | DAS181 OL Wiki | 0.07 |
drug277 | Clevudine Wiki | 0.07 |
drug1072 | Standard of care treatment Wiki | 0.07 |
drug1359 | non-contact magnetically-controlled capsule endoscopy Wiki | 0.07 |
drug800 | Organicell Flow Wiki | 0.07 |
drug1161 | Thrombomodulin Modified Thrombin Generation Assay (TGA-TM) Wiki | 0.07 |
drug1377 | prayer Wiki | 0.07 |
drug658 | Low-dose chloroquine Wiki | 0.07 |
drug314 | Convalescent Plasma from COVID-19 donors Wiki | 0.07 |
drug239 | Camostat Mesilate Wiki | 0.07 |
drug271 | Ciclesonide Inhalation Aerosol Wiki | 0.07 |
drug417 | Etoposide Wiki | 0.07 |
drug352 | Data research, database analysis Wiki | 0.07 |
drug1081 | Standard therapy recommended by the Ministry of Health of the Russian Federation. Wiki | 0.07 |
drug371 | Dipyridamole 100 Milligram(mg) Wiki | 0.07 |
drug765 | No intervention, observational study Wiki | 0.07 |
drug1130 | Telephone follow-up Wiki | 0.07 |
drug1423 | washed microbiota transplantation Wiki | 0.07 |
drug515 | Hydroxychloroquine - Daily dosing Wiki | 0.07 |
drug1057 | Standard Plasma (FFP) Wiki | 0.07 |
drug756 | Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki | 0.07 |
drug656 | Low or upper respiratory tract sample Wiki | 0.07 |
drug492 | High-Titer COVID-19 Convalescent Plasma (HT-CCP) Wiki | 0.07 |
drug490 | High nitrite/NDMA meals Wiki | 0.07 |
drug578 | Inhaled Supplemental Oxygen Wiki | 0.07 |
drug531 | Hydroxychloroquine Sulfate 600 mg twice a day Wiki | 0.07 |
drug1003 | Saline Wiki | 0.07 |
drug382 | Duodenal biopsy Wiki | 0.07 |
drug1332 | lopinavir/ritonavir tablets or Arbidol or chloroquine phosphate Wiki | 0.07 |
drug1370 | peripheral blood draw Wiki | 0.07 |
drug1008 | Saliva Wiki | 0.07 |
drug361 | Detection of anti-COVID-19 antibody level Wiki | 0.07 |
drug524 | Hydroxychloroquine Sulfate + Azithromycin Wiki | 0.07 |
drug893 | Practice details Wiki | 0.07 |
drug1208 | Urine Test Wiki | 0.07 |
drug404 | Emtricitabine/tenofovir disoproxil Wiki | 0.07 |
drug170 | Blood collection on admission and longitudinally Wiki | 0.07 |
drug1007 | Saline with Baby Shampoo Nasal Irrigation Wiki | 0.07 |
drug996 | SARS-Cov2 testing Wiki | 0.07 |
drug1293 | convalescent plasma from recovered COVID 19 donor Wiki | 0.07 |
drug1218 | Vaccine Wiki | 0.07 |
drug1146 | The Vie Scope laryngoscope Wiki | 0.07 |
drug509 | Hydroxychloroquine + Placebo Wiki | 0.07 |
drug171 | Blood collection on their first consultation and 10 to 14 days later Wiki | 0.07 |
drug491 | High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma Wiki | 0.07 |
drug167 | Blood Test Wiki | 0.07 |
drug454 | Ganovo+ritonavir+/-Interferon nebulization Wiki | 0.07 |
drug1049 | Standar of care Wiki | 0.07 |
drug430 | Famotidine Wiki | 0.07 |
drug336 | DAS181 Wiki | 0.07 |
drug568 | Immunoglubulins Wiki | 0.07 |
drug570 | Immunosuppressive Wiki | 0.07 |
drug821 | Pacebo: Calcium citrate Wiki | 0.07 |
drug403 | Emapalumab Wiki | 0.07 |
drug732 | NP-120 (Ifenprodil) Wiki | 0.07 |
drug538 | Hydroxychloroquine as post exposure prophylaxis Wiki | 0.07 |
drug1349 | muscle ultrasound Wiki | 0.07 |
drug415 | Ergoferon Wiki | 0.07 |
drug420 | Examine the impact of COVID-19 during pregnancy Wiki | 0.07 |
drug416 | Escin Wiki | 0.07 |
drug1168 | Tocilizumab Wiki | 0.07 |
drug957 | Remdesivir Wiki | 0.06 |
drug1062 | Standard of Care Wiki | 0.06 |
drug647 | Lopinavir/ritonavir Wiki | 0.06 |
drug1067 | Standard of care Wiki | 0.06 |
drug1060 | Standard care Wiki | 0.06 |
drug612 | Ivermectin Wiki | 0.06 |
drug108 | Azithromycin Wiki | 0.05 |
drug1102 | Supportive Care Wiki | 0.05 |
drug393 | Echocardiography Wiki | 0.05 |
drug268 | Chloroquine phosphate Wiki | 0.05 |
drug739 | Nasal swab Wiki | 0.05 |
drug379 | Doxycycline Wiki | 0.05 |
drug839 | Peripheral blood draw Wiki | 0.05 |
drug565 | Imatinib Wiki | 0.05 |
drug450 | GLS-5300 Wiki | 0.05 |
drug446 | Follow up Wiki | 0.05 |
drug394 | Eculizumab Wiki | 0.05 |
drug173 | Blood draw Wiki | 0.05 |
drug516 | Hydroxychloroquine - Weekly Dosing Wiki | 0.05 |
drug131 | BNT162b1 Wiki | 0.05 |
drug1135 | Telmisartan Wiki | 0.05 |
drug761 | No Intervention Wiki | 0.05 |
drug741 | Nasopharyngeal swab Wiki | 0.05 |
drug274 | Clazakizumab Wiki | 0.05 |
drug79 | Arbidol Wiki | 0.05 |
drug976 | Routine care for COVID-19 patients Wiki | 0.05 |
drug133 | BNT162c2 Wiki | 0.05 |
drug401 | Electronic questionnaire Wiki | 0.05 |
drug1020 | Selinexor Wiki | 0.05 |
drug900 | Probiotic Wiki | 0.05 |
drug1273 | basic treatment Wiki | 0.05 |
drug264 | Chloroquine Sulfate Wiki | 0.05 |
drug731 | NORS (Nitric Oxide Releasing Solution) Wiki | 0.05 |
drug759 | Nivolumab Wiki | 0.05 |
drug130 | BNT162a1 Wiki | 0.05 |
drug1391 | self-administered questionnaire Wiki | 0.05 |
drug132 | BNT162b2 Wiki | 0.05 |
drug1033 | Siltuximab Wiki | 0.05 |
drug762 | No intervention Wiki | 0.05 |
drug1314 | hydroxychloroquine Wiki | 0.04 |
drug306 | Control group Wiki | 0.04 |
drug755 | Nitric Oxide Wiki | 0.04 |
drug637 | Lopinavir / Ritonavir Wiki | 0.04 |
drug175 | Blood sample Wiki | 0.04 |
drug757 | Nitric Oxide Gas Wiki | 0.04 |
drug527 | Hydroxychloroquine Sulfate 200 MG [Plaquenil] Wiki | 0.04 |
drug586 | Interferon Beta-1A Wiki | 0.04 |
drug1082 | Standard treatment Wiki | 0.04 |
drug1129 | Telemedicine Wiki | 0.04 |
drug1133 | Telerehabilitation Wiki | 0.04 |
drug1211 | Usual Care Wiki | 0.04 |
drug1280 | blood sampling Wiki | 0.04 |
drug407 | Enoxaparin Wiki | 0.04 |
drug1268 | anti-SARS-CoV-2 convalescent plasma Wiki | 0.04 |
drug801 | Oseltamivir Wiki | 0.03 |
drug1012 | Sarilumab Wiki | 0.03 |
drug1373 | placebo Wiki | 0.02 |
drug309 | Convalescent Plasma Wiki | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
D003141 | Communicable Diseases NIH | 0.66 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.34 |
D018352 | Coronavirus Infections NIH | 0.30 |
D014777 | Virus Diseases NIH | 0.19 |
D012141 | Respiratory Tract Infections NIH | 0.16 |
D018357 | Respiratory Syncytial Virus Infections NIH | 0.14 |
D012327 | RNA Virus Infections NIH | 0.14 |
D003333 | Coronaviridae Infections NIH | 0.12 |
D004408 | Dysgeusia NIH | 0.10 |
D029424 | Pulmonary Disease, Chronic Obstructive NIH | 0.08 |
D018184 | Paramyxoviridae Infections NIH | 0.08 |
D007251 | Influenza, Human NIH | 0.08 |
D004066 | Digestive System Diseases NIH | 0.07 |
D030341 | Nidovirales Infections NIH | 0.07 |
D005767 | Gastrointestinal Diseases NIH | 0.07 |
D009362 | Neoplasm Metastasis NIH | 0.07 |
D011649 | Pulmonary Alveolar Proteinosis NIH | 0.07 |
D009410 | Nerve Degeneration NIH | 0.07 |
D001997 | Bronchopulmonary Dysplasia NIH | 0.07 |
D008595 | Menorrhagia NIH | 0.07 |
D006470 | Hemorrhage NIH | 0.07 |
D003384 | Coxsackievirus Infections NIH | 0.07 |
D004660 | Encephalitis NIH | 0.07 |
D006929 | Hyperaldosteronism NIH | 0.07 |
D000075902 | Clinical Deterioration NIH | 0.07 |
D003428 | Cross Infection NIH | 0.07 |
D014552 | Urinary Tract Infections NIH | 0.07 |
D054990 | Idiopathic Pulmonary Fibrosis NIH | 0.07 |
D000309 | Adrenal Insufficiency NIH | 0.07 |
D054559 | Hyperphosphatemia NIH | 0.07 |
D007008 | Hypokalemia NIH | 0.07 |
D017250 | Caliciviridae Infections NIH | 0.07 |
D011565 | Psoriasis NIH | 0.07 |
D055501 | Macrophage Activation Syndrome NIH | 0.07 |
D009220 | Myositis NIH | 0.07 |
D009369 | Neoplasms, NIH | 0.06 |
D011014 | Pneumonia NIH | 0.06 |
D008173 | Lung Diseases, Obstructive NIH | 0.06 |
D011024 | Pneumonia, Viral NIH | 0.06 |
D008171 | Lung Diseases, NIH | 0.06 |
D000857 | Olfaction Disorders NIH | 0.05 |
D003139 | Common Cold NIH | 0.05 |
D007154 | Immune System Diseases NIH | 0.05 |
D000257 | Adenoviridae Infections NIH | 0.05 |
D058070 | Asymptomatic Diseases NIH | 0.05 |
D009205 | Myocarditis NIH | 0.05 |
D012140 | Respiratory Tract Diseases NIH | 0.05 |
D011658 | Pulmonary Fibrosis NIH | 0.04 |
D007153 | Immunologic Deficiency Syndromes NIH | 0.04 |
D007676 | Kidney Failure, Chronic NIH | 0.04 |
D003324 | Coronary Artery Disease NIH | 0.04 |
D004211 | Disseminated Intravascular Coagulation NIH | 0.04 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.04 |
D055371 | Acute Lung Injury NIH | 0.04 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.04 |
D020521 | Stroke NIH | 0.04 |
D020141 | Hemostatic Disorders NIH | 0.04 |
D011665 | Pulmonary Valve Insufficiency NIH | 0.04 |
D053120 | Respiratory Aspiration NIH | 0.04 |
D001778 | Blood Coagulation Disorders NIH | 0.04 |
D019337 | Hematologic Neoplasms NIH | 0.03 |
D017563 | Lung Diseases, Interstitial NIH | 0.03 |
D004417 | Dyspnea NIH | 0.03 |
D016638 | Critical Illness NIH | 0.03 |
D012120 | Respiration Disorders NIH | 0.03 |
D006973 | Hypertension NIH | 0.03 |
D018450 | Disease Progression NIH | 0.02 |
D000860 | Hypoxia NIH | 0.02 |
D013577 | Syndrome NIH | 0.02 |
D002318 | Cardiovascular Diseases NIH | 0.02 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0011947 | Respiratory tract infection HPO | 0.16 |
HP:0006510 | Chronic obstructive pulmonary disease HPO | 0.08 |
HP:0000132 | Menorrhagia HPO | 0.07 |
HP:0002905 | Hyperphosphatemia HPO | 0.07 |
HP:0003765 | Psoriasiform dermatitis HPO | 0.07 |
HP:0002900 | Hypokalemia HPO | 0.07 |
HP:0002383 | Encephalitis HPO | 0.07 |
HP:0100614 | Myositis HPO | 0.07 |
HP:0000846 | Adrenal insufficiency HPO | 0.07 |
HP:0002180 | Neurodegeneration HPO | 0.07 |
HP:0006517 | Alveolar proteinosis HPO | 0.07 |
HP:0000859 | Hyperaldosteronism HPO | 0.07 |
HP:0002664 | Neoplasm HPO | 0.06 |
HP:0002090 | Pneumonia HPO | 0.06 |
HP:0006536 | Obstructive lung disease HPO | 0.06 |
HP:0002088 | Abnormal lung morphology HPO | 0.06 |
HP:0000458 | Anosmia HPO | 0.05 |
HP:0012819 | Myocarditis HPO | 0.05 |
HP:0011024 | Abnormality of the gastrointestinal tract HPO | 0.05 |
HP:0002206 | Pulmonary fibrosis HPO | 0.04 |
HP:0001677 | Coronary artery atherosclerosis HPO | 0.04 |
HP:0005521 | Disseminated intravascular coagulation HPO | 0.04 |
HP:0002721 | Immunodeficiency HPO | 0.04 |
HP:0001928 | Abnormality of coagulation HPO | 0.04 |
HP:0001297 | Stroke HPO | 0.04 |
HP:0010444 | Pulmonary insufficiency HPO | 0.04 |
HP:0006515 | Interstitial pneumonitis HPO | 0.03 |
HP:0002098 | Respiratory distress HPO | 0.03 |
HP:0001909 | Leukemia HPO | 0.03 |
HP:0000822 | Hypertension HPO | 0.03 |
HP:0012418 | Hypoxemia HPO | 0.02 |
HP:0001626 | Abnormality of the cardiovascular system HPO | 0.02 |
There are 195 clinical trials
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.Currently, there is no treatment for children less than one year of age with influenza related lower respiratory tract infection that is either considered standard or registered in any country. This dismal scenario exists even though influenza related LRTI is a significant illness causing morbidity and mortality, especially in children less than 6 months of age. Avian influenza has been reported rarely in children less than one. There are no data in Vietnam and very few data in Thailand on the burden of influenza in children less than one. This young age group suffers high mortality. Oseltamivir may be beneficial in such children. This is basis of this trial.
Description: Viral clearance on Day 5 (human influenza) on a throat swab, assessed by RT PCR. Viral clearance on Day 10 (avian influenza) on a throat swab, assessed by RT PCR.
Measure: Viral clearance Time: 5-10 daysDescription: • Cmax, Tmax, AUC, apparent volume of distribution, clearance, terminal elimination half-life
Measure: Pharmacokinetics of Oseltamivir Time: Day 0 and Day 9Description: Time to viral clearance on a throat swab, assessed by RT PCR. The time to no detectable influenza virus by culture for the throat swab. Change in viral load (log10 copies/mL) over time for all virological samples (lower limit of detection: 1000 copies/mL) Viral susceptibility of cultured influenza virus to antiviral drugs at baseline and post treatment, assessed by genotypical and phenotypical analyses
Measure: Viral end points Time: 5-10 daysDescription: Time to fever clearance In hospital mortality and mortality by follow up Time to death Time to trans cutaneous O2 saturation of ≥ 95% on room air Clinical course: pneumothorax, encephalitis/encephalopathy Number of days in hospital Number of days ventilated
Measure: Clinical Efficacy Endpoints Time: 5-10 daysDescription: Documented serious adverse events (SAEs) and relationships to oseltamivir AEs leading to drug withdrawal Grade 3 & 4 clinical and laboratory AEs that are probably or definitely related to oseltamivir Skin rashes of any grade Changes in haematological and biochemical parameters over time
Measure: Safety Endpoints Time: 5-10 daysInfectious disease is the single biggest cause of death worldwide. New infectious agents,such as the Severe Acute Respiratory Syndrome coronavirus and new strains of influenza continually emerge and require new investigations to understand pathogen biology and pathogenesis in the host. Witness the Influenza A pandemic. Concerns about new viruses and their impact on health and the economy are also increasing. Current alerts sent out by the Ministry of Health (about the novel coronavirus and the Avian influenza A virus) are but cases in point. These likely reflect advances in science, which have allowed novel pathogens to be identified. Because of its geography, Singapore is vulnerable to new pathogens through importation or the global travel of its citizens. Hence we must be ever ready to meet unexpected challenges anytime. On the administrative front, Singapore General Hospital has a Disease Outbreak Task-force which has in place many plans that can be activated should there be a large-scale epidemic. What is missing thus far is a program that will enable us to perform scientific studies in the setting of an epidemic. Hence in this study, we will, in collaboration with the Program in Emerging Infectious Diseases (EID) in Duke-National University of Singapore Postgraduate Medical School, attempt to (i) detect novel, previously undescribed pathogens; (ii) characterize viruses (not necessarily novel but emerging and re-emerging) that are raising concern or causing clusters or epidemics in the hospital and/or country; (iii) characterize immune responses to such viruses in healthcare workers as well as patients (those affected by these viruses and those exposed to the affected). The techniques that will be used will be those not routinely available in a hospital's service labs. Some patients will remain undiagnosable with the best available technology. Since new laboratory tools that can detect previously undiagnosed pathogens may become available in the future, the study also aims to archive specimens from patients whose illnesses remain undiagnosed.
Description: Clinical data collection through case records, and interview of patients or next-of-kin or friend in the event information is unavailable or incompletely documented in the case records. Sample collection will be performed according to the following frequency: First day of enrolment: blood draw (by weight) not more than 20ml, nasal (and/or nasopharyngeal ) and/or throat swab, stool and urine sample. On days 2, 3, 5, 7, 10, 14 and 28: blood (by weight) not more than 10 ml, nasal (and/or nasopharyngeal l) and/or throat swab, stool and urine sample. On D28, blood (by weight) not more than 20ml, will be drawn as most immune response changes manifest by then. If available, urine and stool sample will be collected. If the subject is intubated, endotracheal aspirate will replace nasal and throat swab. Sample collection for research will be done at the same time as samples for clinical testing as far as possible, to minimize patient discomfort.
Measure: Detecting of Novel Pathogens Time: Day 1 - Day 28 of recruitmentThe primary objective of this study is to evaluate the effects of presatovir on respiratory syncytial virus (RSV) viral load in RSV-positive adults who have been hospitalized with acute respiratory infectious symptoms. Participants will receive 1 dose of presatovir on Day 1 and followed for 27 days postdose. Nasal swabs will be collected at each study visit (excluding Day 28) and assayed for change in viral load as the primary endpoint.
Description: The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.
Measure: Time-Weighted Average Change in Respiratory Syncytial Viral (RSV) Load From Baseline to Day 5 Time: Baseline to Day 5Description: The Flu-PRO is a patient-reported outcome questionnaire utilized as a standardized method for evaluating symptoms of influenza. Flu-PRO Score was calculated as the mean of 38 individual scores. Individual scores ranged from 0 (no symptoms) to 4 (worst symptoms). The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.
Measure: Time-weighted Average Change in the Flu-PRO Score From Baseline to Day 5 Time: Baseline to Day 5Description: The adjusted rate of unplanned medical encounters (clinic visits, emergency room visits, urgent care visits, and rehospitalizations) related to a respiratory illness after initial hospital discharge through Day 28 will be assessed. Event rate was calculated as the total number of unplanned medical encounters divided by the total number of participants. The mean values presented were adjusted for stratification factor.
Measure: Rate of Unplanned Medical Encounters Time: Up to Day 28The primary objective of this study is to evaluate the effect of presatovir on respiratory syncytial virus (RSV) viral load in autologous or allogeneic hematopoietic cell transplant (HCT) recipients with an acute RSV upper respiratory tract infection (URTI), the effect of presatovir on development of lower respiratory tract complication, being free of any supplemental oxygen progression to respiratory failure, and pharmacokinetics (PK), safety, and tolerability of presatovir.
Description: The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.
Measure: Time-Weighted Average Change in Nasal Respiratory Syncytial Virus (RSV ) Viral Load From Baseline (Day 1) to Day 9 Time: Baseline; Day 9Description: A Lower Respiratory Tract Complication (LRTC) was defined as one of the below as determined by the adjudication committee: Primary RSV lower respiratory tract infection (LRTI) Secondary bacterial LRTI LRTI due to unusual pathogens Lower respiratory tract complication of unknown etiology
Measure: Percentage of Participants Who Developed a Lower Respiratory Tract Complication Time: Up to Day 28Description: Participants were considered to have an event if either condition is met: Participant develops a respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) or; Participant dies prior to or on Day 28
Measure: Percentage of Participants Who Developed Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality Time: Up to Day 28The primary objective of this study is to evaluate the effect of presatovir on respiratory syncytial virus (RSV) viral load in autologous or allogeneic hematopoietic cell transplant (HCT) recipients with an acute RSV lower respiratory tract infection (LRTI).
Description: The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factors.
Measure: Time-weighted Average Change in Nasal Respiratory Syncytial Viral (RSV) Load From Baseline to Day 9 Time: Baseline to Day 9The purpose of this study is to determine if the use of inhaled beclomethasone after a community-acquired respiratory viral infection in a lung transplant recipient decreases the risk of the subsequent development of chronic lung allograft dysfunction.
This study aimed to analysis the characteristics of MERS transmission and the effect of our institutional personal protective equipment on the controlling the MERS at a tertiary Korean Hospital.
The objective of this project is to study the prevalence of viruses and bacteria responsible for transmissible acute respiratory infections in the respiratory tract of pilgrims returning from the trip. The patients included, will be the consultant pilgrims to the traveler health center, and before leaving for Hajj. Based on the results obtained in previous studies, it is estimated that 200 pilgrims will be included each year, 600 in total (inclusion period of 3 years). Respiratory secretions are then collected by nasal swab and throat (swab) prior to departure for the hajj. In return, patients will be reconvened systematic consultation to record medical events potentially encountered during the trip, and it will again be performed the same nasal swabs and throat. It will then be performed on these samples' return from hajj "molecular detection (PCR and RT-PCR) of 35 viruses and bacteria respiratory tropism: influenza (3), RSV (2), metapneumovirus (1), Coronavirus (4), Parainfluenzavirus (4), enteroviruses (4), rhinovirus (1), adenovirus (6) bocavirus, polyomavirus (2), pneumococcus, Bordetella pertussis, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Coxiella burnetii. Samples "return of hajj" positive should be cultured for the isolation of the strain. For patients positive return, it will be done further research of these 35 viruses and bacteria on samples "start of hajj," the same method described above. In addition to this systematic consultation, and if symptoms return, the pilgrims will be seen in consultation for a diagnosis evaluation and therapeutic management. This study will shed light on the acquisition of microorganisms respiratory tropism during the stay and on the potential risks associated with the circulation of these pathogens after the trip.
The international multicenter double-blind placebo-controlled randomized clinical study in parallel groups.The objective of this study is to obtain additional data on the efficacy and safety of Ergoferon in the treatment of acute respiratory viral infections (ARVI) in children aged from 6 months to 6 years old.
Description: Based on patient diary data. Criteria of alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome.
Measure: Time to Alleviation of All ARVI Symptoms. Time: 14 days of observation.Description: Based on patient diary data. Oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period).
Measure: Time to Normalization of Body Temperature. Time: 14 days of observation.Description: Based on patient diary data. Absence of flu-like nonspecific symptoms/presence of one mild flu-like nonspecific symptom.
Measure: Time to Alleviation of Flu-like Nonspecific Symptoms. Time: 14 days of observation.Description: Based on patient diary data. Absence of respiratory symptoms/presence of one mild respiratory symptom.
Measure: Time to Alleviation of Respiratory Symptoms. Time: 14 days of observation.Description: Based on patient diary data. The total score (TS) ranges from 0 to 30 consisting of 4 flu-like nonspecific (decreased activity/weakness, poor appetite/refusal to eat, sick appearance, sleep disturbance) and 6 respiratory (runny nose, stuffy nose/nasal congestion, sneezing, hoarseness, sore throat, cough) symptoms according to the 4-point scale for each symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome.
Measure: Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6. Time: On days 2-6 of the observation period.Description: Based on the area under the curve of TS for days 2-6, according to the patient diary. The total score (TS) will be calculated based on the severity of each ARVI symptom (sum of 11 symptoms = body temperature, flu-like nonspecific symptoms (4 symptoms) and respiratory symptoms (6 symptoms) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TS the absolute oral temperature values, measured in degrees Celsius, will be converted into relative units (or points), given the following gradations: ≤37.5С = 0 point; 37.6-38.1C = 1 point; 38.2-38.8C = 2 points; ≥38.90С = 3 points. For total score minimum and maximum scores are 0 and 33, where higher values represent a worse outcome.
Measure: ARVI Severity. Time: On days 2-6 of the observation period.Description: Based on patient diary data. Criteria of recovery/alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale for each flu-like nonspecific and respiratory symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom).
Measure: Percentage of Recovered Patients. Time: On days 2-6 of the observation period.Description: Based on patient diary data. The number of intakes of prescribed antipyretics.
Measure: Rates of Antipyretics Use Per Patient. Time: On days 1- 5 of the treatment period.Description: Based on patient diary data. The disease worsening: ARVI complications, including those requiring antibiotics; hospitalization).
Measure: Percentage of Patients With Worsening of Illness. Time: 14 days of observation peiod.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 26The primary objective in this study is to establish a list of host cellular proteins that mediate norovirus infection. Norovirus is one of the most common pathogens attributed to diarrheal diseases from unsafe food. It is also the primary cause of mortality among young children and adults in foodborne infections. Norovirus is not just a foodborne burden. In a recent meta-analysis, norovirus accounts for nearly one-fifth of all causes of (including person-to-person transmission) acute gastroenteritis in both sporadic and outbreak settings and affects all age groups. Undoubtedly, norovirus is of paramount public health concern in both developed and developing countries. Research efforts to better understand norovirus pathobiology will be necessary for targeted intervention. From Middle East respiratory syndrome coronavirus to Zika virus, efforts to identify host factors important for mediating virus infection has always been a research priority. Such information will shed light on potential therapeutic targets in antiviral intervention. Norovirus virus-host interaction studies have been hampered by the lack of a robust cell culture model in the past 20 years. In 2016, norovirus has finally been successfully cultivated in a stem cell-derived three-dimensional human gut-like structure called enteroid or mini-gut. In this study, intestinal stem cells will be isolated from duodenal biopsies collected from participants, followed by differentiation into mini-guts. Genome-wide genetic screening for host essential and restrictive factors will be performed on infected mini-guts by knockout CRISPR and gain-of-function CRISPR SAM, respectively. Shortlisted candidates will undergo preliminary functional validation in cell lines. These data will provide insights into potential therapeutic targets against norovirus infection.
Description: Viability of enteroids as determined by microscopy
Measure: Establishment of human intestinal stem cell-derived enteroids Time: An average of three monthsThis study will seek to enroll immunocompromised patients with Lower Tract parainfluenza infection. It also contains a sub-study to enroll patients with severe COVID-19.
Description: Removal of all oxygen support (with stable SpO2)
Measure: Percent of subjects who Return to Room Air (RTRA) (main study) Time: by Day 28In the general population, increased WBCC and neutrophil count are widely used as markers for infection during inflammatory states 1. However, 32% of geriatric patients with an infection do not develop an increase in WBCC 2. The hypothesis is that with inflammation, geriatric patients have a misadapted response of the immune system (IS) 3. Our recent retrospective study 4 has shown that total and differential WBCC were not correlated with infection in a geriatric hospitalized population. Therefore, WBCC does not seem to be a reliable marker for infection in geriatric hospitalized patients. The neutrophil/lymphocyte ratio, and CRP, seem to be better markers. the aim of the study to investigate this hypothesis prospectively and assess the role of aging and chronic diseases (such as cardiovascular diseases (CVD) and risk factors (CVRF) 5, cytomegalovirus (CMV) infection 6, periodontitis 7, onychomycosis 8 ) in this process and assess the role of a geriatric assessment. To assess the usefulness of WBCC in the diagnosis of infection in geriatric patients and to address the contribution of ongoing chronic co-morbidities and age to WBCC-kinetics during an acute inflammatory syndrome, young and geriatric hospitalized patients with an inflammatory syndrome with and without infection will be compared
Description: observation of WBCC is correlated with infection by older patient
Measure: Usefulness of white blood cell count (WBCC) during infection in geriatric patient Time: 1.5 yearsThe purpose of this study is to evaluate the effect of JNJ-53718678 on the development of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTIs) in adult hematopoietic stem cell transplant (HSCT) recipients with RSV upper RTI.
Description: The proportion of participants who develop RSV LRTI through Visit Day 28 per the Endpoint Adjudication Committee (EAC) assessment will be reported.
Measure: Proportion of Participants who Develop Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI) Time: Up to Day 28Description: The proportion of participants who develop RSV-associated LRTC through Visit Day 28 per the EAC's assessment will be reported.
Measure: Proportion of Participants who Develop RSV-associated Lower Respiratory Tract Complication (LRTC) Time: Up to Day 28Description: An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Measure: Number of Participants with Adverse Events (AEs) Time: Up to 49 DaysDescription: Percentage of participants with abnormal clinical laboratory findings will be reported.
Measure: Percentage of Participants with Abnormal Clinical Laboratory Findings Time: Up to 49 daysDescription: Percentage of participants with abnormal ECGs findings will be reported.
Measure: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings Time: Up to 49 daysDescription: Percentage of participants with abnormal vital signs findings will be reported.
Measure: Percentage of Participants with Abnormal Vital Signs Findings Time: Up to 49 daysDescription: The proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment Time: Up to 49 daysDescription: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, (all-cause mortality) will be reported.
Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, (all-cause Mortality) Time: Up to 49 daysDescription: Proportion of participants progressing to death (all-cause mortality), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Measure: Proportion of Participants Progressing to Death (All-cause Mortality), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment Time: Up to 49 daysDescription: Proportion of participants progressing to death (all-cause mortality) will be reported.
Measure: Proportion of Participants Progressing to Death (All-cause Mortality) Time: Up to 49 daysDescription: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment Time: Up to 49 daysDescription: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) will be reported.
Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) Time: Up to 49 daysDescription: Number of supplemental O2 free days will be reported.
Measure: Number of Supplemental Oxygen (O2) Free Days Through Day 28 Time: Through Day 28Description: Incidence of supplemental oxygen requirement in participants will be reported.
Measure: Incidence of Supplemental Oxygen Requirement Time: Up to 28 daysDescription: Duration of supplemental oxygen requirement in participants will be reported.
Measure: Duration of Supplemental Oxygen Time: Up to 28 daysDescription: Change from baseline in respiratory rate as measured by the investigator during scheduled visits will be reported.
Measure: Change from Baseline in Respiratory Rate Time: Baseline up to 49 daysDescription: Change from baseline in heart rate as measured by the investigator during scheduled visits will be reported.
Measure: Change from Baseline in Heart Rate Time: Baseline up to 49 daysDescription: Change from baseline in SpO2 as measured by the investigator during scheduled visits will be reported.
Measure: Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2) Time: Baseline up to 49 daysDescription: Change from baseline in body temperature as measured by the investigator during scheduled visits will be reported.
Measure: Change from Baseline in Body Temperature Time: Baseline up to 49 daysDescription: Proportion of participants hospitalized (of participants who were not hospitalized at baseline) will be reported.
Measure: Proportion of Participants Hospitalized (of Participants who Were not Hospitalized at Baseline) Time: Up to 49 daysDescription: Proportion of participants re-hospitalized (of participants who were hospitalized at baseline and discharged during the study and of participants who were not hospitalized at baseline, required hospitalization, and were discharged during the study) will be reported.
Measure: Proportion of Participants Re-hospitalized Time: Up to 49 daysDescription: Total length of hospital stay (time in hospital from first dosing) will be reported.
Measure: Total Length of Hospital Stay Time: Up to 49 daysDescription: Total time in the ICU (time in ICU from first dosing) will be reported.
Measure: Total Time in the Intensive Care Unit (ICU) Time: Up to 49 daysDescription: Incidence of Grade 3 and Grade 4 AEs will be assessed by system organ class where Grade 3: Severe and Grade 4: Life-threatening.
Measure: Incidence of Grade 3 and Grade 4 Adverse Events (AEs) Time: Up to 49 daysDescription: Incidence of respiratory AEs will be reported.
Measure: Incidence of Respiratory AEs Time: Up to 49 daysDescription: Incidence of thoracic-related AEs will be reported.
Measure: Incidence of Thoracic-related AEs Time: Up to 49 daysDescription: Incidence of antibiotic use in participants who develop and in those who do not develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Measure: Incidence of Antibiotic use in Participants who Develop and in Those who do not Develop RSV LRTI or RSV-Associated LRTC per the EAC's Assessment Time: Up to 49 daysDescription: Time to resolution of symptoms, assessed through an instrument for participant-reported symptoms (RiiQ Symptom Scale) will be reported.
Measure: Time to Resolution of Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale Time: Up to 49 daysDescription: Change from baseline in severity of symptoms reported by participants in the RiiQ symptom scale through Day 28 will be reported.
Measure: Change from Baseline in Severity of Symptoms Reported by Participants in the RiiQ Symptom Scale Through Day 28 Time: Baseline up to Day 28Description: Time to resolution of respiratory illness, through the PGI-S Scale, will be reported.
Measure: Time to Resolution of Respiratory Illness as Assessed by Patient Global Impression of Severity (PGI-S) Scale Time: Up to 49 daysDescription: Change from baseline in PGI-H scale through Day 28 will be reported.
Measure: Change from Baseline in Patient Global Impression of Health (PGI-H) Scale Through Day 28 Time: Baseline up to Day 28Description: Change from baseline in PGI-C scale through Day 28 will be reported.
Measure: Change from Baseline in Patient Global Impression of Change (PGI-C) Scale Through Day 28 Time: Baseline up to Day 28Description: AUC (0-24h) is defined as area under the plasma concentration-time curve from time 0 to 24 hours postdose.
Measure: Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours Postdose (AUC [0-24]) of JNJ-53718678 Time: Up to 24 hours postdose (on Days 1 and 8)Description: Ctrough is defined as the observed plasma concentration before dosing or at the end of the dosing interval.
Measure: Trough Plasma Concentration (Ctrough) of JNJ-53718678 Time: Predose on Days 1 and 8Description: Cmax is defined as the maximum observed plasma concentration of JNJ-53718678 in the dosing interval.
Measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 Time: Predose; 0.5, 1, 1.5, 2, 4, 8, 24 hours postdose (on Days 1 and 8)Description: The potential association of plasma concentration-time data of JNJ-53718678 with antiviral activity (RSV viral kinetics) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.
Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Antiviral Activity Time: Up to 49 daysDescription: The potential association of plasma concentration-time data of JNJ-53718678 with selected safety (including AEs and laboratory abnormalities) parameters will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.
Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Safety Parameters Time: Up to 49 daysDescription: The potential association of plasma concentration-time data of JNJ-53718678 with clinical outcomes (proportion of participants developing LRTI) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.
Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Clinical Outcomes Time: Up to 49 daysDescription: RSV viral load and change from baseline over time will be measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in the mid-turbinate nasal swab specimens.
Measure: RSV Viral Load and Change from Baseline Over Time Time: Baseline up to Day 28Description: RSV viral load AUC will be determined by quantitative qRT-PCR assay of nasal swabs.
Measure: RSV Viral Load AUC from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 8, 11, 15, 22 and 28 Time: Baseline up to Days 8, 11, 15, 22 and 28Description: Time to undetectable RSV viral load (per the detection limit of the assay used in the study) will be reported.
Measure: Time to Undetectable RSV Viral Load Time: Up to 49 daysDescription: Proportion of participants with undetectable RSV viral load at each time point throughout the study will be reported.
Measure: Proportion of Participants with Undetectable RSV Viral Load at Each Timepoint Time: Up to 49 daysDescription: Change from baseline for the HRQOL assessment as assessed through the EQ-5D-5L through Day 28 will be reported.
Measure: Change from Baseline for the Health-related Quality of Life (HRQOL) as Assessed by 5-level EuroQol 5-Dimension (EQ-5D-5L) Through Day 28 Time: Baseline up to Day 28Description: Change from baseline for the HRQOL assessment as assessed through RiiQ impact scales through Day 28 will be reported.
Measure: Change from Baseline for the HRQOL as Assessed by RiiQ Impact Scales Through Day 28 Time: Baseline up to Day 28Description: Change from baseline in the RSV F gene sequence will be reported.
Measure: Change from Baseline in the RSV F Gene Sequence Time: Baseline up to 49 daysIn this multi-center, randomized, control study, the investigators will evaluate the efficacy and safety of glucocorticoid in combination with standard care for COVID-19 patents with Severe acute respiratory failure.
Description: Murray lung injury score decreased more than one point means better outcome.The Murray scoring system range from 0 to 16 according to the severity of the condition.
Measure: Lower Murray lung injury score Time: 7 days after randomizationDescription: Murray lung injury score decreased more than one point means better outcome.The Murray scoring system range from 0 to 16 according to the severity of the condition.
Measure: Lower Murray lung injury score Time: 14 days after randomizationDescription: PaO2/FiO2 denotes ratio of arterial partial pressure of O2 and the fraction of inspired oxygen, with a higher PaO2/FiO2 means favorable outcome.
Measure: The difference of PaO2/FiO2 between two groups Time: 7 days after randomizationDescription: Lower SOFA score means better outcome. The SOFA score system range from 0 to 24 according to the severity of the condition.
Measure: Lower Sequential Organ Failure Assessment (SOFA) score Time: 7 days after randomizationDescription: Percentage of patients requiring Mechanical ventilation support
Measure: Mechanical ventilation support Time: 7 days after randomizationDescription: PaO2/FiO2 denotes ratio of arterial partial pressure of O2 and the fraction of inspired oxygen, with a higher PaO2/FiO2 means favorable outcome.
Measure: The difference of PaO2/FiO2 between two groups Time: 14 days after randomizationDescription: Lower SOFA score means better outcome. The SOFA score system range from 0 to 24 according to the severity of the condition.
Measure: Lower Sequential Organ Failure Assessment (SOFA) score Time: 14 days after randomizationDescription: Percentage of patients requiring Mechanical ventilation support
Measure: Mechanical ventilation support Time: 14 days after randomizationDescription: Clearance of noval coronavirus in upper respiratory tract or lower respiratory tract
Measure: Clearance of noval coronavirus Time: 14 days after randomizationDescription: All-cause mortality
Measure: All-cause mortality Time: 30 days after randomizationGut dysbiosis co-exists in patients with coronavirus pneumonia. Some of these patients would develop secondary bacterial infections and antibiotic-associated diarrhea (AAD). The recent study on using washed microbiota transplantation (WMT) as rescue therapy in critically ill patients with AAD demonstrated the important clinical benefits and safety of WMT. This clinical trial aims to evaluate the outcome of WMT combining with standard therapy for patients with 2019-novel coronavirus pneumonia, especially for those patients with dysbiosis-related conditions.
Description: Common type: Fever, respiratory tract and other symptoms, imaging examination shows pneumonia; Severe type (meeting any of the following): (1) Respiratory distress,respiratory rate ≥ 30 bmp; (2) Oxygen saturation ≤ 93%;(3)PaO2/FiO2 ≤ 300mmHg. Critically severe type (meeting any of the following): (1) Respiratory failure requiring mechanical ventilation; (2) Shock; (3) Combining with other organ failures, requiring ICU monitoring and treatment.
Measure: Number of participants with improvement from severe type to common type Time: 2 weeksThe 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 21Infectious 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 study is designed to clarify the clinical characteristics, risk factors and long-term prognosis of children with 2019-nCoV infection in China.
Description: Percentage
Measure: The cure rate of 2019-nCoV. Time: 6 monthsDescription: Percentage
Measure: The improvement rate of 2019-nCoV. Time: 6 monthsDescription: Days
Measure: Duration of fever Time: 2 weeksDescription: Days
Measure: Duration of respiratory symptoms Time: 2 weeksDescription: Days
Measure: Duration of hospitalization Time: 2 weeksA 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, viral pneumonia caused by a novel beta-coronavirus (Covid-19) broke out in Wuhan, China. Some patients rapidly progressed and suffered severe acute respiratory failure and died, making it imperative to develop a safe and effective vaccine to treat and prevent severe Covid-19 pneumonia. Based on detailed analysis of the viral genome and search for potential immunogenic targets, a synthetic minigene has been engineered based on conserved domains of the viral structural proteins and a polyprotein protease. The infection of Covid-19 is mediated through binding of the Spike protein to the ACEII receptor, and the viral replication depends on molecular mechanisms of all of these viral proteins. This trial proposes to develop and test innovative Covid-19 minigenes engineered based on multiple viral genes, using an efficient lentiviral vector system (NHP/TYF) to express viral proteins and immune modulatory genes to modify dendritic cells (DCs) and to activate T cells. In this study, the safety and efficacy of this LV vaccine (LV-SMENP) will be investigated.
Description: A decline of 2 points on the 7-point scale from admission means better outcome. The 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death).
Measure: Clinical improvement based on the 7-point scale Time: 28 days after randomizationDescription: Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition.
Measure: Lower Murray lung injury score Time: 7 days after randomizationDescription: Number of deaths during study follow-up
Measure: 28-day mortality Time: Measured from Day 0 through Day 28Description: Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up.
Measure: Duration of mechanical ventilation Time: Measured from Day 0 through Day 28Description: Days that a participant spent at the hospital. Multiple hospitalizations are summed up.
Measure: Duration of hospitalization Time: Measured from Day 0 through Day 28Description: Proportion of patients with negative RT-PCR results of virus in upper and/or lower respiratory tract samples.
Measure: Proportion of patients with negative RT-PCR results Time: 7 and 14 days after randomizationDescription: Proportion of patients in each category of the 7-point scale, the 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death).
Measure: Proportion of patients in each category of the 7-point scale Time: 7,14 and 28 days after randomizationDescription: Proportion of patients with different inflammation factors in normalization range.
Measure: Proportion of patients with normalized inflammation factors Time: 7 and 14 days after randomizationDescription: Frequency of vaccine/CTL Events
Measure: Frequency of vaccine/CTL Events Time: Measured from Day 0 through Day 28Description: Frequency of Serious vaccine/CTL Events
Measure: Frequency of Serious vaccine/CTL Events Time: Measured from Day 0 through Day 28The 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.
Since December 2019, there has been an outbreak of novel coronavirus pneumonia in China. As of February 18, 2020, 72,530 cases confirmed with 2019 coronavirus disease(COVID-19) have been reported and 1,870 deaths were declared. Until now, cases of COVID-19 have been reported in 26 countries. This observational study aims to analysis the clinical features of neonates with COVID-19 and the neonates born to mother with COVID-19.
Description: Neonates born to mothers with COVID-19 will be tested for SARS-CoV-2 after birth.Confirmed cases will meet the diagnosed criterion provided by National Health and Health Commission and the Chinese perinatal-neonatal SARS-CoV-2 Committee.
Measure: The SARS-CoV-2 infection of neonates born to mothers with COVID-19 Time: within 7days after the admissionDescription: The standardized DDST consists of 104 items and covers four areas of development: (a) personal/social, (b) fine motor/adaptive, (c) language, and (d) gross motor. In the present study, three trained professionals examined the children. The results of the DDST could be normal (no delays), suspect (2 or more caution items and/or 1 or more delays), abnormal (2 or more delays) or untestable (refusal of one or more items completely to the left of the age line or more than one item intersected by the age line in the 75-90% area). The children with suspect or abnormal results were retested 2 or 3 weeks later.
Measure: The Chinese standardized Denver Developmental Screening Test (DDST) in neonates with or with risk of COVID-19 Time: Infants ( ≥35 weeks)are at 6 months after birth;Infants(< 35weeks) are at a corrected age of 6 months.Description: The small for gestational age infant is defined as live-born infants weighting less than the 10th percentile for gestational age (22 weeks+0 day to 36 weeks+6days).
Measure: The small for gestational age newborns in the neonates born to mothers with COVID-19 Time: at birthDescription: The preterm infant is defined as the gestational age less than 37weeks+0day.The gestational age range is 22 weeks+0 day to 36 weeks+6days
Measure: The preterm delivery of neonates born to mothers with COVID-19 Time: at birthDescription: Infants with SARS-CoV-2 infection are classified into asymptomatic, mild infection and severe infection, according to the expert consensus provided by the Chinese
Measure: The disease severity of neonates with COVID-19 Time: through study completion, estimated an average of 2 weeksSince 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 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 daysThe 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 daysEvaluation of the efficacy and safety of Ganovo combined with ritonavir for patients infected with SARS-CoV-2.
Description: Defined as SPO2≤ 93% without oxygen supplementation, PaO2/FiO2 ≤300mmHg or a respiratory rate ≥30 breaths per min without supplemental oxygen
Measure: Rate of composite adverse outcomes Time: 14 daysDescription: Clinical recovery was defined as 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).
Measure: Time to recovery Time: 14 daysDescription: Rate of no fever
Measure: Rate of no fever Time: 14 daysDescription: Rate of no cough
Measure: Rate of no cough Time: 14 daysDescription: Rate of no dyspnea
Measure: Rate of no dyspnea Time: 14 daysDescription: Rate of no requiring supplemental oxygen
Measure: Rate of no requiring supplemental oxygen Time: 14 daysDescription: Rate of undetectable New coronavirus pathogen nucleic acid
Measure: Rate of undetectable New coronavirus pathogen nucleic acid Time: 14 daysDescription: Rate of mechanical ventilation
Measure: Rate of mechanical ventilation Time: 14 daysDescription: Rate of ICU admission
Measure: Rate of ICU admission Time: 14 daysDescription: Rate of serious adverse event
Measure: Rate of serious adverse event Time: 14 daysThis is a Phase IIb study consisting of two cohorts to evaluate efficacy, safety and pharmacokinetics of DAS181 in IFV infection. An approximate total of 280 subjects will be enrolled into this study.
Description: Percent of subjects who have returned to room air
Measure: Percent of subjects who have returned to room air Time: 7 daysDescription: Percent change of subjects return to baseline oxygen requirement by Day 7 compared to Day 1
Measure: Percent change of subjects return to baseline oxygen requirement Time: 7 daysIn December 2019 a new kind of virus was identified in China as the responsible of severe acute respiratory syndrome (SARS) and interstitial pneumonia. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread around the world and in February 2020 became a pandemia in Europe. No pharmacological treatment is actually licensed for the SARS-CoV2 infection and at the current state of art there is a lack of data about the clinical management of the coronavirus 2019 disease (COVID-19). The aim of this observational study is to collect the data and the outcomes of COVID-19 patients admitted in the H. Sacco Respiratory Unit treated according to the Standard Operating Procedures and the Good Clinical Practice.
Description: Data collection about the real life management of patients affected by SARS-CoV-2 infection with acute respiratory distress syndrome
Measure: Real life data of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection Time: 1-6 monthsDescription: How many patients died during the hospitalization
Measure: in-hospital mortality Time: 1 monthDescription: How many patients died 30 days after the discharge
Measure: 30 days mortality Time: 1 monthDescription: How many patients died 6 months after the discharge
Measure: 6 months mortality Time: 6 monthsDescription: How many patients were intubated during the hospitalization
Measure: Intubation rate Time: 7 daysDescription: How many days/hours from admittance to intubation
Measure: Time to Intubation Time: 7 daysDescription: How many days/hours from admittance to the start of non invasive ventilation or CPAP therapy
Measure: Time to ventilation Time: 7 daysDescription: How many days/hours from the start of non invasive ventilation or CPAP therapy to the intubation
Measure: Non invasive to Invasive time Time: 7 daysDescription: How many patients were healed from the infection and discharged
Measure: Recovery rate Time: 1 monthDescription: How many patients underwent re-infection after previous recovery from COVID19
Measure: Recurrence rate Time: 1 monthDescription: Assessment of the risk factors for the infection and the admission to the hospital
Measure: Risk factor for COVID19 Time: retrospectiveDescription: What serological parameter could be used as predictor of good or negative prognosis.
Measure: Blood tests and outcome Time: 1 monthDescription: Impact of antiviral therapy on the clinical course of the disease
Measure: Antiviral therapy Time: 1 monthDescription: Assessment of bacterial, fungal or other coinfections rate
Measure: Coinfections Time: 1 monthDescription: Impact of radiological findings on the clinical course and the outcome
Measure: Radiological findings Time: 1 monthDescription: Impact of ultrasound findings on the clinical course and the outcome
Measure: Ultrasound findings Time: 1 monthDescription: Assessment of the evidence of myocardial injury in covid19+ patients
Measure: Myocardial injury Time: 1 monthDescription: impact of standard therapeutic operating procedures (eg enteral nutrition, hydration, drugs) on the clinical course.
Measure: Medical management Time: 1 monthStudy Objective: 1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
Description: Number of participants at 14 days post enrollment with active COVID19 disease.
Measure: Incidence of COVID19 Disease among those who are asymptomatic at baseline Time: 14 daysDescription: Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall change in disease severity over 14 days among those who are symptomatic at baseline Time: 14 daysDescription: Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Measure: Incidence of Hospitalization Time: 14 daysDescription: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Measure: Incidence of Death Time: 90 daysDescription: Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Measure: Incidence of Confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID19 infection.
Measure: Incidence of Symptoms Compatible with COVID19 (possible disease) Time: 90 daysDescription: Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Measure: Incidence of All-Cause Study Medicine Discontinuation or Withdrawal Time: 14 daysDescription: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall symptom severity at 5 and 14 days Time: 5 and 14 daysDescription: Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.
Measure: Ordinal Scale of COVID19 Disease Severity at 14 days among those who are symptomatic at trial entry Time: 14 daysThis is a multi-center, double-blinded study of COVID-19 infected patients randomized 1:1 to daily losartan or placebo for 10 days or treatment failure (hospital admission).
Description: Outcome reported as the number of participants per arm admitted to inpatient hospital care due to COVID-19-related disease within 15 days of randomization. Currently, there is a pre-planned pooled analysis with a national trial network under development.
Measure: Hospital Admission Time: 15 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.
Measure: Change in PROMIS Dyspnea Functional Limitations Time: baseline, 10 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.
Measure: Change in PROMIS Dyspnea Severity Time: baseline, 10 daysDescription: Participants will report their maximum daily oral temperature to the study team. Outcome is reported as the mean maximum daily body temperature (in degrees Celsius) over 10 days.
Measure: Daily Maximum Temperature Time: 10 daysDescription: Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.
Measure: Emergency Department/Clinic Presentations Time: 28 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 7 Time: 7 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 15 Time: 15 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 28 Time: 28 daysDescription: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Oropharyngeal Swab Day 9 Time: 9 daysDescription: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Oropharyngeal Swab Day 15 Time: 15 daysDescription: Outcome reported as the mean number of days participants in each arm did not require ventilator use.
Measure: Ventilator-Free Days Time: 28 daysDescription: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen use.
Measure: Therapeutic Oxygen-Free Days Time: 28 daysDescription: Outcome reported as the percent of participants in each arm who require hospital admission by day 15 following randomization.
Measure: Need for Hospital Admission at 15 Days Time: 15 daysDescription: Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.
Measure: Need for Oxygen Therapy at 15 Days Time: 15 daysThis is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.
Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.
Measure: Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days Time: 7 daysDescription: Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm.
Measure: Daily Hypotensive Episodes Time: 10 daysDescription: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Measure: Hypotension Requiring Vasopressors Time: 10 daysDescription: Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.
Measure: Acute Kidney Injury Time: 10 daysDescription: The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.
Measure: Sequential Organ Failure Assessment (SOFA) Total Score Time: 10 daysDescription: Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.
Measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S) Time: 10 daysDescription: Outcome reported as the number of participants who have expired at 28 days post enrollment.
Measure: 28-Day Mortality Time: 28 daysDescription: Outcome reported as the number of participants who have expired at 90 days post enrollment.
Measure: 90-Day Mortality Time: 90 daysDescription: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Measure: ICU Admission Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
Measure: Number of Ventilator-Free Days Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.
Measure: Number of Therapeutic Oxygen-Free Days Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
Measure: Number of Vasopressor-Free Days Time: 10 daysDescription: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
Measure: Length of ICU Stay Time: 10 daysDescription: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
Measure: Length of Hospital Stay Time: 10 daysDescription: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.
Measure: Incidence of Respiratory Failure Time: 10 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.
Measure: Change in PROMIS Dyspnea Functional Limitations Time: 10 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.
Measure: Change in PROMIS Dyspnea Severity Time: 10 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Time: 10 daysDescription: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Nasopharyngeal Swab Day 9 Time: 9 daysDescription: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Nasopharyngeal Swab Day 15 Time: 15 daysDescription: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Blood Day 9 Time: 9 daysDescription: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Blood Day 15 Time: 15 daysThousands of healthcare workers have been infected with SARS-CoV-2 and contracted COVID-19 despite their best efforts to prevent contamination. No proven vaccine is available to protect healthcare workers against SARS-CoV-2. This study will enroll 470 healthcare professionals dedicated to care for patients with proven SARS-CoV-2 infection. Subjects will be randomized either in the observational (control) group or in the inhaled nitric oxide group. All personnel will observe measures on strict precaution in accordance with WHO and the CDC regulations.
Description: Percentage of subjects with COVID-19 diagnosis in the two groups
Measure: COVID-19 diagnosis Time: 14 daysDescription: Percentage of subjects with a positive test in the two groups
Measure: Positive SARS-CoV-2 rt-PCR test Time: 14 daysDescription: Mean/ Median in the two groups
Measure: Total number of quarantine days Time: 14 daysDescription: Percentage in the two groups
Measure: Proportion of healthcare providers requiring quarantine Time: 14 daysAdults who have tested positive for SARS-CoV-2 infection and who do not require supplemental oxygen will receive PUL-042 Inhalation Solution or placebo 3 times over a one week period in addition to their normal care. Subjects will be be followed and assessed for their clinical status over 28 days to see if PUL-042 Inhalation Solution improves the clinical outcome
Description: To determine the efficacy of PUL-042 Inhalation Solution in decreasing the severity of COVID-19 in subjects: 1) who have documented SARS-CoV-2 infection and, 2) who do not require supplemental oxygen (Ordinal Scale for Clinical Improvement 3 or less) at the time of enrollment. The primary endpoint is the difference in the proportion of patients with clinically meaningful worsening of COVID-19 within 28 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.
Measure: Severity of COVID-19 Time: 28 daysDescription: SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy
Measure: SARS-CoV-2 infection Time: 28 daysDescription: To determine the difference in the proportion of COVID-19 patients with clinically meaningful worsening of COVID-19 within 14 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.
Measure: Severity of COVID-19 over 14 days Time: 14 daysDescription: To assess the progression of COVID-19 severity during the study as measured by the SARS-CoV-2 Symptom Score. The SARS-CoV-2 Symptom Score measures 3 elements on a 0-3 scale (cough, shortness of breath or difficulty breathing, and muscle aches or fatigue) ranging from 0 for none to 3 for severe. The fourth element is fever and it is rated on a 0-4 scale with 0 being no fever and 4 being life-threatening.
Measure: Severity of COVID-19 symptoms Time: 28 daysDescription: The requirement for ICU admission within 28 days from the start of the experimental therapy.
Measure: ICU admission Time: 28 daysDescription: The requirement for mechanical ventilation within 28 days from the start of the experimental therapy.
Measure: Mechanical Ventilation Time: 28 daysDescription: All cause mortality at 28 days from the start of experimental therapy
Measure: Mortality Time: 28 daysSubjects who have documented exposure to SARS-CoV-2 (COVID-19) will receive 4 doses of PUL-042 Inhalation Solution or 4 doses of a placebo solution by inhalation over 10 days. Subjects will be followed for the incidence and severity of COVID-19 over 28 days. Subjects will be tested for infection with SARS-CoV-2 at the beginning, middle and end of the study.
Description: To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with SARS-CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to individuals with SARS-CoV-2 infection and, 2) are asymptomatic at enrollment. The primary endpoint is the severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 28 days from the start of experimental therapy.
Measure: Severity of COVID-19 Time: 28 daysDescription: Positive test for SARS-CoV-2 infection 28 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit
Measure: Incidence of SARS-CoV-2 infection Time: 28 daysDescription: Positive test for SARS-CoV-2 infection 14 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit
Measure: Incidence of SARS-CoV-2 infection Time: 14 daysDescription: The severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 14 days from the start of experimental therapy.
Measure: Severity of COVID-19 Time: 14 daysDescription: The requirement for ICU admission within 28 days from the start of experimental therapy.
Measure: ICU admission Time: 28 daysDescription: The requirement for mechanical ventilation within 28 days from the start of experimental therapy.
Measure: Mechanical ventilation Time: 28 daysDescription: All cause mortality at 28 days from the start of experimental therapy.
Measure: Mortality Time: 28 daysIn 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 daysCollection 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)Coronavirus Disease 19 (COVID-19) represents an unprecedented challenge to the operations and population health management efforts of health care systems around the world. The "Pandemic Research Network (PRN): Duke Community Health Watch" study leverages technology, clinical research, epidemiology, telemedicine, and population health management capabilities to understand how to safely COVID-19. The target population is individuals in the Duke Health region as well as individuals beyond the Duke Health region who have flu-like symptoms, a viral test order for COVID-19, confirmed COVID-19, or concern for exposure to COVID-19. A subgroup of particular interest within the target population is health care workers (HCW) and families of HCW. Community members will enroll in the study electronically and for 28 days will be reminded via email or SMS to submit signs and symptoms related to COVID-19. Participants who report symptoms will be provided information about COVID-19 testing (if needed) and established mechanisms to seek care within Duke Health. Instructions for telemedicine and in-person visits, which is available publicly at https://www.dukehealth.org/covid-19-update, will be presented to participants. Participants who are unable to report symptoms independently may be contacted via telephone by Population Health Management Office (PHMO) or Clinical Events Classification (CEC) team members. Data collected through the "Pandemic Response Network (PRN): Duke Community Health Watch" study will be used for three objectives. - First, to characterize the epidemiological features of COVID-19. Specifically, we will have a high-risk subgroup of HCW and families of HCW that we enroll. - Second, to develop models that predict deterioration and the need for inpatient care, intensive care, and mechanical ventilation. - Third, to develop forecast models to estimate the volume of inpatient and outpatient resources needed to manage a COVID-19 population. The primary risk to study participants is loss of protected health information. To address this concern, all data will be stored in Duke's REDCap instance and the Duke Protected Analytics Compute Environment (PACE).
SARS-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 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 randomizationCoronavirus (COVID-19) is a somewhat new and recognized infectious disease that is now spreading to several countries in the world, including Brazil. Hydroxychloroquine and azithromycin may be useful for treating those patients. COALITION I study aims to compared standard of care, hydroxychloroquine plus azithromycin and hydroxychloroquine monotherapy for treatment of hospitalized patients with COVID-19. COALITION I will recruit 630 patients with infection by COVID-19 (210 per arm). Ordinal endpoint of status at 15 days will be the primary endpoint.
Description: Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 7 points. Alive at home without limitations on activities Alive at home without limitations on activities In the hospital without oxygen In the hospital using oxygen In the hospital using high-flow nasal catheter or non-invasive ventilation In hospital, on mechanical ventilation Dead
Measure: Evaluation of the clinical status Time: 15 days after randomizationDescription: Evaluation of the clinical status of patients on the 7th day after randomization defined by the Ordinal Scale of 7 points. Alive at home without limitations on activities Alive at home without limitations on activities In the hospital without oxygen In the hospital using oxygen In the hospital using high-flow nasal catheter or non-invasive ventilation In hospital, on mechanical ventilation Dead
Measure: Ordinal scale in 7 days Time: 7 days after randomizationDescription: Need of intubation and mechanical ventilation up to the 7th day after randomization
Measure: Need of intubation and mechanical ventilation Time: 7 days after randomizationDescription: Use of mechanical ventilation during hospital stay
Measure: Use of mechanical ventilation during hospital stay Time: 15 days after randomizationDescription: Use of non-invasive ventilation up to the 7th day after randomization
Measure: Use of non-invasive ventilation Time: 7 days after randomizationDescription: Hospital Length of Stay
Measure: Hospital Length of Stay Time: 28 days after randomizationDescription: All-cause mortality rates during hospital stay
Measure: All-cause mortality Time: 28 days after randomizationDescription: Occurrence of thromboembolic complications such as: Deep vein thrombosis Pulmonary Embolism Stroke
Measure: Thromboembolic complications Time: 15 days after randomizationDescription: Occurrence of renal dysfunction, defined as an increase in creatinine above 1.5 times the baseline value
Measure: Acute renal disfunction Time: 15 days after randomizationDescription: Number of days alive and free of respiratory support up to 15 days (DAFOR15), defined as the sum of days patients did not require supplementary oxygen, non-invasive ventilation, high-flow nasal catheter neither mechanical ventilation at 15 -days. Patients that perished during the 15-day window will receive zero DAFOR15.
Measure: Number of days alive and free of respiratory support up to 15 days Time: 15 daysDescription: Corrected QT interval
Measure: Safety outcome on corrected QT interval Time: At day 3 and 7 after enrollmentThis observational study will collect data from patients treated under a compassionate use programme with siltuximab (SYLVANT); patients diagnosed with COVID-19 infection who have developed serious respiratory complications. This observational study will group the patients into two cohorts receiving siltuximab. Patients in Cohort A are treated in a non-ICU setting and patients in Cohort B are in an ICU setting. Each patient will have a matched control receiving standard treatment without siltuximab
Description: reduction of the need of invasive ventilation or 30-day mortality
Measure: Cohort A: reduction of the need of invasive ventilation or 30-day mortality Time: 30 daysDescription: reduction of mortality
Measure: Cohort B: reduction of mortality Time: 30 daysIn December 2019,a new type of pneumonia caused by the coronavirus (COVID-2019) broke out in Wuhan ,China, and spreads quickly to other Chinese cities and 28 countries. More than 70000 people were infected and over 2000 people died all over the world. There is no specific drug treatment for this disease. Considering that lung damage is related to both viral infection and burst of cytokines, our idea is to evaluate the efficacy and safety of escin as add-on treatment to conventional antiviral drugs in COVID-19 infected patients.
Description: All cause mortality
Measure: Mortality rate Time: up to 30 daysDescription: mild type:no No symptoms, Radiological examination: no pneumonia; possible mild increase in C-reactive portein 2, moderate type: fever, cough, or other respiratory symptoms. Radiological examination: pneumonia, SpO2>93% without oxygen inhalation ; increase in C reactive protein, 3: severe type: a. Rate ≥30bpm;b. Pulse Oxygen Saturation (SpO2)≤93% without oxygen inhalation,c. PaO2/FiO2(fraction of inspired oxygen )≤300mmHg ;4. Critically type:match any of the follow: a. need mechanical ventilation; b. shock; c. (multiple organ dysfunction syndrome) MODS
Measure: Clinical status evaluated in agreement with guidelines Time: up to 30 daysDescription: Pulse Oxygen Saturation(SpO2)>93%,1. No need for supplemental oxygenation; 2. nasal catheter oxygen inhalation(oxygen concentration%,The oxygen flow rate:L/min);3. Mask oxygen inhalation(oxygen concentration%,The oxygen flow rate:L/min);4. Noninvasive ventilator oxygen supply(Ventilation mode,oxygen concentration%,The oxygen flow rate:L/min,);5. Invasive ventilator oxygen supply(Ventilation mode,oxygen concentration%,The oxygen flow rate:L/min,)
Measure: The differences in oxygen intake methods Time: up to 30 daysDescription: days
Measure: Time of hospitalization (days) Time: up to 30 daysDescription: days
Measure: Time of hospitalization in intensive care units Time: up to 30 daysDescription: forced expiratory volume at one second ,maximum voluntary ventilation at 1month,2month,3month after discharge
Measure: Pulmonary function Time: up to 3 months after dischargeThis study explores whether patients acutely hospitalized may have shorter hospitalization and fewer admittances at Intensive Care Units by treatment with azithromycin and hydroxychloroquine.
Description: The patient will becategorized into one of the following 8 categories depending on status of their hospitalization: Dead (yes/no) Hospitalized and receiving mechanical ventilation or ExtraCorporalMembraneOxygenation (ECMO) (yes/no) Hospitalized and receiving Non-invasive ventilation or "high-flow oxygen device" (yes/no) Hospitalized and given oxygen supplements different from (2) and (3) (yes/no) Hospitalized and without oxygen treatment, but receiving other treatment (both related to COVID-19 or other) (yes/no) Hospitalized for observation (yes/no) Discharged from hospital with restriction of activity level (yes/no) Discharged from hospital without any restrictions of activity level (yes/no) Only one category can be "yes".
Measure: Categorization of hospitalization status Time: 14 daysDescription: Delta PaO2 measured in arterial puncture
Measure: Change in patient's oxygen partial pressure Time: 4 daysDescription: Delta PaCO2 measured in arterial puncture
Measure: Change in patient's carbondioxid partial pressure Time: 4 daysDescription: pH measured in arterial puncture
Measure: Level of pH in blood Time: 4 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, Neuron-Specific Enolase, 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, Neuron-Specific Enolase, IL-2, IL-6, TNF-alfa, leukocytes, subtypes lymphocytes) after treatment Time: 60 daysThe primary objective of this study is to provide expanded access of remdesivir (RDV) for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection.
As shown by the data available, hyper-inflammation, caused by a cytokine storm resulting from an exaggerated response of the immune system to the presence of the virus, is considered to represent one of the most important negative prognostic factor in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study is to investigate new possibilities to reduce the number of patients requiring mechanical ventilation. This is intended to address the most urgent need to preserve the access to intensive care unit support to the lowest possible number of patients and may potentially reduce mortality.
Description: Defined as the proportion of patients not requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)
Measure: Treatment success Time: Up to Day 15Description: Measured in days
Measure: Time to mechanical ventilation Time: Date of randomization to date of mechanical ventilationDescription: Measured in total score
Measure: Change from baseline in Modified Early Warning system score Time: Baseline, Day 15Description: Measured in percent (%)
Measure: Change from baseline in resting peripheral capillary oxygen saturation (SpO2) Time: Baseline, 3 assessments every Days 4, 7, 10, 13 and 15Description: Measured in percent (%)
Measure: Change from baseline in partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) Time: Baseline, Day 15Description: Measured in local units
Measure: Change of pH in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of carbon dioxide tension (pCO2) in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of oxygen tension (pO2) in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of potassium in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of sodium in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of chloride in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of lactic acid in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change of hemoglobin in hemogasanalysis from baseline Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in l/min
Measure: Change from baseline in oxygen supplementation Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in scan evaluation: Normal, Abnormal but not clinically significant, Abnormal clinical significant, Not Done
Measure: Change of findings of high-resolution computed tomography (CT) scan of the chest Time: Screening, Day 15Description: Measured in local units
Measure: Change from baseline in Ferritin Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in lactate dehydrogenase (LDH) Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in D-dimers Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in White Blood Cells with differential counts Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Red Blood Counts Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Hemoglobin Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Platelet count Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Fibrinogen Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Complement factors C3/C4 Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Prothrombin time Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Cardiac troponin Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in aspartate aminotransferase (AST) Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in alanine aminotransferase (ALT) Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in total bilirubin levels Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in C-Reactive Protein Time: Baseline, Days 4, 7, 10, 13 and 15Description: Measured in local units
Measure: Change from baseline in Creatinine Time: Baseline, Days 4, 7, 10, 13 and 15Description: Confirmation of death
Measure: Overall survival Time: Weeks 6 and 10Description: Measured in days
Measure: Time to hospital discharge Time: Weeks 6 and 10This study will assess the prevalence and incidence of COVID-19 infection in patients with chronic plaque psoriasis on immunosuppressant therapy.
COVID-19 Viral Global Pandemic resulting in post-infection pulmonary damage, including Fibrotic Lung Disease due to inflammatory and reactive protein secretions damaging pulmonary alveolar structure and functionality. A short review includes: - Early December, 2019 - A pneumonia of unknown cause was detected in Wuhan, China, and was reported to the World Health Organization (WHO) Country Office. - January 30th, 2020 - The outbreak was declared a Public Health Emergency of International Concern. - February 7th, 2020 - 34-year-old Ophthalmologist who first identified a SARS-like coronavirus) dies from the same virus. - February 11th, 2020 - WHO announces a name for the new coronavirus disease: COVID-19. - February 19th, 2020 - The U.S. has its first outbreak in a Seattle nursing home which were complicated with loss of lives.. - March 11th, 2020 - WHO declares the virus a pandemic and in less than three months, from the time when this virus was first detected, the virus has spread across the entire planet with cases identified in every country including Greenland. - March 21st, 2020 - Emerging Infectious Disease estimates the risk for death in Wuhan reached values as high as 12% in the epicenter of the epidemic and ≈1% in other, more mildly affected areas. The elevated death risk estimates are probably associated with a breakdown of the healthcare system, indicating that enhanced public health interventions, including social distancing and movement restrictions, should be implemented to bring the COVID-19 epidemic under control." March 21st 2020 -Much of the United States is currently under some form of self- or mandatory quarantine as testing abilities ramp up.. March 24th, 2020 - Hot spots are evolving and identified, particularly in the areas of New York-New Jersey, Washington, and California. Immediate attention is turned to testing, diagnosis, epidemiological containment, clinical trials for drug testing started, and work on a long-term vaccine started. The recovering patients are presenting with mild to severe lung impairment as a result of the viral attack on the alveolar and lung tissues. Clinically significant impairment of pulmonary function appears to be a permanent finding as a direct result of the interstitial lung damage and inflammatory changes that accompanied. This Phase 0, first-in-kind for humans, is use of autologous, cellular stromal vascular fraction (cSVF) deployed intravenously to examine the anti-inflammatory and structural potential to improve the residual, permanent damaged alveolar tissues of the lungs.
Description: Reporting of Adverse Events or Severe Adverse Events Assessed by CTCAE v4.0
Measure: Incidence of Treatment-Emergent Adverse Events Time: 1 monthDescription: High Resolution Computerized Tomography of Lung (HRCT Lung) for Fluidda Analysis comparative at baseline and 3 and 6 months post-treatment comparative analytics
Measure: Pulmonary Function Analysis Time: baseline, 3 Month, 6 monthsDescription: Finger Pulse Oximetry taken before and after 6 minute walk on level ground, compare desaturation tendency
Measure: Digital Oximetry Time: 3 months, 6 monthsAn open access study that will define and collect digital measures of coughing in multiple populations and public spaces using various means of audio data collection.
Description: Size of collected audio dataset measured as number of collected cough sounds, targeting ≥10,000 identified coughs.
Measure: Dataset size Time: 14 daysDescription: Identification of cough sounds by the existing mathematical model with ≥ 99% specificity and ≥ 60% sensitivity
Measure: Cough sound identification Time: 14 daysDescription: Increase in the sensitivity of the mathematical model to cough sounds to ≥ 70% while retaining the specificity of ≥ 99%
Measure: Improvement of the existing model Time: 14 daysDescription: Determination of the level of acceptance and satisfaction of the solution by patients by means of a Standard Usability Questionnaire to provide feedback. The score ranges from 10 to 50, higher score indicating a better usability.
Measure: Evaluate the usability of the application Time: 14 days7. Objectives To apply e-health methods to perform active monitoring and assess determinants of incident Infection of COVID-19 in a hospital population. 8. Study design Prospective, Single-centre, observational clinical study. 9. Disease or disorder under study Healthy people in risk of COVID-19 infection. 10. Main variable. Symptoms related to infection caused by SARS-Cov2. 11. Study population and total number of patients Men and women in general god health status aged between 18 and 80 years that currently are employees of Hospital de La Princesa . 12. Duration of treatment Each subject will be monitored, since its recruitment, for a period of 12 weeks. 13. Timetable and expected date of completion The overall duration of the study is estimated at about 6 months, from patient recruitment to the last data recorded by last subject. The aim is to carry out this study from March 2020 onwards.
Description: The primary objective of this trial is to investigate whether the use of a cell phone App-based platform is a useful tool to monitor the symptoms of a population in risk of SARS-Cov2 infection. The final aim is to assess determinants of incidence of infection of COVID-19 in people working in Hospital during the pandemia of SARS-Cov-2.
Measure: COVID-19 App-based platform Time: 6 monthsDescription: To monitor in real-time COVID-19 symptoms in the hospital workforce, which are a proxy of incident infection (Step 1) To identify in real-time clusters of COVID-19 symptoms and to facilitate control measures. To determine the incidence of new infection of COVID-19. To identify the determinants and risk/protective factors associated with this infection, in a workforce hospital population free of COVID-19 at the start of our study.
Measure: COVID-19 infection Time: 6 monthsThis is a randomized, double-blind placebo-controlled trial to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-19 infection. On evaluation for enrollment, participant will need to meet all inclusion and exclusion criteria. If participant consents, they will be randomized 1:1 to treatment with either tradipitant 85 mg PO BID or placebo in addition to standard of care for COVID-19 infection as per the protocol at the treating hospital. NEWS 2 will be assessed at screening and daily following randomization. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.
This study will utilize a single center internal control study design. The objective of this study is to determine the feasibility and safety of a bidirectional oxygenation PEEP generating mouthpiece when combined with oxygen by non-rebreather face mask, compared to support by oxygen non-rebreather face mask alone.
Description: The primary endpoint for this feasibility study is pulse oximetry level after treatment with a Bidirectional Oxygenation Valve
Measure: Pulse oximetry level Time: Change from Baseline pulse oximetry level at 15 minutes post treatmentDescription: Venous and arterial blood gases, if available, will be combined to report systemic carbon dioxide.
Measure: Systemic carbon dioxide Time: Change from Baseline clinical measurements at 15 minutes post treatmentCoronavirus 2019 (COVID-19) is a respiratory tropism virus transmitted through droplets emitted into the environment of infected persons. The symptoms can be extremely varied and the course can range from spontaneous healing without sequelae to death. Currently, the diagnosis of certainty for resuscitation patients (by definition "severe") is based on searching for a fragment of virus genetic material within the epithelial cells of the respiratory tree, up and/or down, by PCR. It is to be expected that the epidemic peak will make it difficult (if not impossible) to respect the stereotypical path that is currently in place, due to the lack of space in the specific unit. This will require optimization of care pathways and use of the specific sectors. It is therefore necessary to define the simple criteria, available from the moment patients are admitted, to predict the result of the COVID-19 PCR.
Description: Assessment of viral, bacterial, fungal and parasitic rate in confirmed and unconfirmed patients for COVID-19
Measure: Coinfections Time: during ICU stay, up to 28 daysDescription: it will be reported the evolution of respiratory dysfunction in patients infected with COVID-19 admitted to ICU during their stay and requiring mechanical ventilation (during, Pao2/FIO2 ratio,,features of artificial ventilation features of extra-bodied respiratory assistance)
Measure: Respiratory dysfunction requiring mechanical ventilation Time: during ICU stay, up to 28 daysDescription: the SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure).
Measure: Sequential Organ Failure Assessment (SOFA) Score Time: during ICU stay, up to 28 daysDescription: APS II was designed to measure the severity of disease for patients admitted to Intensive care units 24 hours after admission to the ICU, the measurement has been completed and resulted in an integer point score between 0 and 163 and a predicted mortality between 0% and 100%.
Measure: SAPS II score Time: at admissionDescription: The DIC Score was developed by the The International Society of Thrombosis and Haemostasis (ISTH.) The DIC score calculator accounts of the following four parameters.Each of the four parameters evaluated above have values that are weighted with a number of points varying from 0 to 3. By summing the points given to the choices, a final result between 0 and 8 is obtained
Measure: Disseminated Intravascular Coagulation (DIC) score Time: during ICU stay, up to 28 daysDescription: measuring the long-term impact of confirmed COVID-19 infection. assessment of quality of life according to 8 areas: physical activity (and related limitations), body pain, perception of one's own health, mental health (and related limitations), social life and vitality.
Measure: Short Form 36 Time: at 9 months +/- 3 months after ICU stayDescription: The scale allows to detect anxiety and depression using 14 items rated from 0-3. Measuring the long-term impact of confirmed COVID-19 infection
Measure: Hospital anxiety and depression scale (HADS) Time: at 9 months +/- 3 months after ICU stayDescription: 22-item self-report measure that assesses subjective distress caused by traumatic events Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88) Measuring the long-term impact of confirmed COVID-19 infection
Measure: Impact of Event Scale - revised (IES-R) Time: at 9 months +/- 3 months after ICU stayDescription: Question the stressful experience or event, followed by 20 multiple-choice questions. Measuring the long-term impact of confirmed COVID-19 infection
Measure: Post-traumatic stress disorder Checklist version DSM-5 (PSL-5) Time: at 9 months +/- 3 months after ICU stayDescription: The mMRC Dyspnea Scale stratifies severity of dyspnea in respiratory diseases Measuring the long-term impact of confirmed COVID-19 infection
Measure: Modified Medical Research Council (MMRC) Dyspnea Scale Time: at 9 months +/- 3 months after ICU stayDescription: Evolution of viral clearance in nasal and depp PCR during ICU
Measure: Viral clearance Time: through study completion, an average of 28 daysThis 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 yearsSince December 2019, the emergence of a new coronavirus named SARS-Cov-2 in the city of Wuhan in China has been responsible for a major epidemic of respiratory infections, including severe pneumonia. Within weeks, COVID-19 became a pandemic. In the absence of specific antiviral treatment, a special attention should be given to prevention. Personal protection equipments may be insufficiently protective, including in healthcare workers, a significant proportion of whom (around 4%) having been infected in the outbreaks described in China and more recently in Italy. Infection in healthcare workers could result from the contact with COVID-19 people in community or with infected colleagues or patients. As it will take at least a year before vaccines against SARS-CoV-2 becomes available, chemoprophylaxis is an option that should be considered in this setting where prevention of SARS-CoV-2 infection in Health Care Workers. The COVIDAXIS trial evaluates a chemoprophylaxis of SARS-CoV-2 infection in Health Care Workers. This trial is divided into two distinct studies that could start independently each with its own randomization process: COVIDAXIS 1 will study Hydroxychloroquine (HCQ) versus placebo; COVIDAXIS 2 will study Lopinavir/ritonavir (LPV/r) versus placebo. Upon randomization healthcare workers (HCWs) involved in the management of suspected or confirmed COVID-19 cases will be assigned to one of the following 2 treatment groups:
Description: An infection by SARS-CoV-2 is defined by either: a positive specific Reverse Transcription - Polymerase Chain Reaction (RT-PCR) on periodic systematic nasopharyngeal swab during follow-up OR a positive specific RT-PCR on a respiratory sample in case of onset of symptoms consistent with COVID-19 during follow-up OR a seroconversion to SARS-CoV-2 after randomization.
Measure: Occurrence of an symptomatic or asymptomatic SARS-CoV-2 infection among healthcare workers (HCWs) Time: Up to 2.5 monthsDescription: Number of adverse events expected or unexpected, related and unrelated to the treatment, notably grades 2, 3 and 4 (moderate, severe and lifethreatening, according to the Adverse National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0) in each arm.
Measure: Evaluation of the occurrence of adverse events in each arm, Time: Up to 2.5 monthsDescription: Number of treatment discontinuations in each arm
Measure: Evaluation of the discontinuation rates of the investigational drug in each arm, Time: Up to 2 monthsDescription: Treatment adherence rate will be assessed by: measurement of LPV and HCQ plasma concentrations using LC-MS/MS or LC-Fluorimetric detection the count of returned drugs at each visit.
Measure: Evaluation of the adherence of participants to study drug, Time: Up to 2 monthsDescription: Number of incident cases of symptomatic SARS-CoV-2 infections among HCWs in each arm. Symptomatic infection is defined as : a positive specific RT-PCR on a respiratory or non respiratory sample OR a thoracic CT scan with imaging abnormalities consistent with COVID-19. These investigations being performed in case of signs/symptoms consistent with COVID-19 during follow-up.
Measure: Evaluation of the incidence of symptomatic cases of SARS-CoV-2 infection in each arm, Time: Up to 2.5 monthsDescription: Number of incident cases of asymptomatic SARS-CoV-2 infection among HCWs in each randomization arm. Asymptomatic infection is defined as : a positive specific RT-PCR on periodic systematic nasopharyngeal swab during clinical follow-up without consistent clinical signs/symptoms during follow-up OR as seroconversion to SARS-CoV-2 between start and end of the study in HCWs that did not reported any consistent clinical symptoms during follow-up
Measure: Evaluation of the incidence of asymptomatic cases of SARS-CoV-2 infection in each arm Time: Up to 2.5 monthsDescription: Number of incident cases of severe SARS-CoV-2 infections among HCWs in each randomization arm, defined as : a positive specific RT-PCR on a respiratory sample OR a thoracic CT scan with imaging abnormalities consistent with COVID-19 performed in case of onset of symptoms consistent with COVID-19 during follow-up in a participant who need to be hospitalized for respiratory distress. Respiratory distress defined as dyspnea with a respiratory frequency > 30/min, blood oxygen saturation <93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300 and/or lung infiltrates >50% (1).
Measure: Evaluation of the incidence of severe cases of SARS-CoV-2 infection in each arm. Time: Up to 2.5 monthsDescription: Safety. Electrocardiogram (ECG)
Measure: corrected QT interval (ms) Time: At baseline, at D2 (only for COVIDAXIS 1) and every week up to 2 months.COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate potential therapeutics for the treatment of hospitalized COVID-19. We hypothesis that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid declines in viral load in throat swabs. This viral attenuation should be associated with improved patient outcomes. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19. The study is funded and leaded by The Ministry of Health, Vietnam.
Description: Viral presence will be determined using RT-PCR to detect SARS-CoV-19 RNA. Throat swabs for viral RNA will be taken daily while in hospital until there have at least 2 consecutive negative results . Virus will be defined as cleared when the patient has had ≥2 consecutive negative PCR tests. The time to viral clearance will be defined as the time following randomization to the first of the negative throat swabs.
Measure: Viral clearance time Time: Up to 56 days post randomizationDescription: The time since randomization to discharge between study groups
Measure: Lengh of hospital stay Time: Up to 56 days post randomizationDescription: The number of ventilator free days over the first 28 days of treatment
Measure: Ventilator free days Time: first 28 daysDescription: The number of oxygene free days over the first 28 days of treatment
Measure: Oxygene free days Time: first 28 daysDescription: The time to (all-cause) death following over the first 7, 10, 14, 28 and 56 days since randomization
Measure: Time to death Time: first 7, 10, 14, 28 and 56 days since randomizationDescription: The rates of serious adverse events, rates of grade 3 or 4 adverse events
Measure: Adverse events Time: Over the first 28 days (due to the prolonged half-life of Chloroquine)Description: Time since randomization to the first viral PCR negative from rectal swab
Measure: Time to viral PCR negative from rectal swab Time: During the first 56 days post randomizationDescription: Time since randomization to the first defervescence day
Measure: fever clearance time Time: Up to 56 days post randomizationDescription: WHO Ordinal outcome scale for COVID-19
Measure: Ordinal outcome scale Time: Up to 56 days post randomizationDescription: Development of ARDS defined by the Kigali criteria
Measure: Development of ARDS Time: Up to 56 days post randomizationThis 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 enrolmentSince December 2019, a novel coronavirus called SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused an international outbreak of respiratory illness described as COVID-19. Individuals with a history of cardiovascular disease develop a more severe illness and have higher rates of death. Because of the potential interaction between RAS blockers and SARS-CoV-2 mechanism of infection, there are ongoing scientific discussions on whether they should be stopped or continued in patients with COVID-19. It is crucial to determine whether RAS blockers should be discontinued or not in patients with COVID-19.
The investigators plan to evaluate a strategy of chemoprophylaxis with hydroxyloquine (HCQ) against COVID-19 infection in patients diagnosed with an immunomediated inflammatory disease who are following a treatment with biological agents and / or Jak inhibitors. The strategy will be carried out through a randomised double blind, placebo-controlled clinical trial and will assess comparative rates of infection (prevalence, incidence), severity including mortality, impact on clínical course of the primary diseases and toxicity. Such evaluation will require prospective surveillance to assess the different end-points. Drug interventions in this protocol will follow the Spanish law about off-label use of medicines.
Description: number of new cases divided by number of persons-time at risk
Measure: Incidence rate of new COVID-19 cases in both arms Time: From day 14 after start of treatment up to the end of follow-up: week 27Description: percentage of cases of COVID 19
Measure: Prevalence of COVID-19 cases in both arms Time: 27 weeks after the beginning of the studyDescription: Case fatality rate (CFR): the proportion of diagnosed cases of COVID 19 that lead to death
Measure: Mortality rate secondary to COVID-19 cases in both groups Time: 27 weeks after the beginning of the studyDescription: percentage of patients who need admission in an ICU due to COVID 19 infection
Measure: Intensive Care Unit (CU) admission rate secondary to COVID-19 cases in both groups Time: 27 weeks after the beginning of the studyDescription: Presence and type of adverse events at this point.
Measure: Adverse events Time: 12 weeks after the start of treatmentDescription: Proportion of participants that drop out of study
Measure: Adverse events Time: 27 weeks after the beginning of the studyWe hypothesize that inhaled steroid therapy and long acting beta 2 adrenergic agonist, widely prescribed in asthma patients, may also have a local protective effect against coronavirus infection, even in patients without asthma. The primary purpose is To compare time to clinical improvement in patients receiving standard of care associated to the combination budesonide/formoterol or standard of care only. Time (in days) to clinical improvement is defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first within 30 days.
Description: Time (in days) to clinical improvement is defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first within 30 days. The seven-category ordinal scale consisted of the following categories: Not hospitalized with resumption of normal activities Not hospitalized, but unable to resume normal activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; Hospitalized, requiring ECMO, invasive mechanical ventilation, or both Death. These parameters will be evaluated daily during hospitalization.
Measure: Time (in days) to clinical improvement within 30 days after randomization Time: within 30 daysThe coronavirus disease 2019 (COVID-19) outbreak is now considered as a public health emergency of international concern by the World Health Organization. In the context of the health emergency, research on the pathogen (the SARS-CoV-2 coronavirus), the disease and the therapeutic care is being organized. Research projects require the use of biological samples. This study aims at setting up a collection of biological samples intended for application projects in any discipline. The main objective of the study is to collect, process and store biological samples from patients and caregivers infected with SARS-CoV-2 (COVID-19) at the biological ressources center of the Bordeaux University Hospital.
Description: From blood samples: protein levels, whole genome sequence, transcriptomic analysis data. From upper respiratory samples: protein levels, virus transcriptomic analysis data. From stool: microbiota analysis data. From urine: protein level.
Measure: COVID-19 desease description Time: Inclusion visit (Day 1)Description: From blood samples: protein levels.
Measure: COVID-19 desease description Time: Day 30 to 90ORCHID 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 randomizationIn order to assess the efficacy of hydroxychloroquine treatment weekly for a total of 7 weeks in the prevention of COVID-19 infection, three hundred sixty (360) Healthcare workers with high risk exposure to patients infected with COVID-19 will be tested for COVID-19 infection via nasopharyngeal (NP) swab once weekly for 7 weeks. Of those, one hundred eighty (180) will receive weekly doses of hydroxychloroquine for the duration of the study. Subjects who opt not to receive the study drug will form the control group.
Description: Rate of COVID-19 positive conversion on weekly nasopharyngeal (NP) sampling
Measure: Rate of COVID-19 positive conversion Time: 7 weeksDescription: Time-to-first clinical event consisting of a persistent change for any of the following: One positive NP sample Common clinical symptoms of COVID-19 infection including fever, cough, and shortness of breath Less common signs and symptoms of COVID-19 infection including headache, muscle pain, abdominal pain, sputum production, and sore throat
Measure: Time-to-first clinical event Time: 7 weeksDescription: Time-to-first clinical worsening event consisting of any of the following: Hospitalization for COVID-19 infection Intensive care unit admission for COVID-19 infection All cause death
Measure: Time-to-first clinical worsening event Time: 7 weeksDesynchronization of infection rates in healthcare workers will potentially reduce the early infection rates and therefore maintain workforce for late time points of the epidemic. Given the current threat of the COVID-19 epidemic, the department for Visceral Surgery and Medicine, Bern University Hospital, has decided to limit its elective interventions to oncological and life-saving procedures only. At the same time, the medical team were split in two teams, each working for 7 days, followed by 7 days off, called a desynchronization strategy. Contacts between the two teams are avoided. The main aim of present study is to determine, if the infection rate between the two populations (at work versus at home) is different. Secondary aims are to determine if the workforce can be maintained for longer periods compared standard of care, and if the infection rate among patients hospitalized for other reasons varies compared to the community.
Description: To determine the infection rate of healthcare workers providing healthcare versus those who are staying at home, in a desynchronization work strategy
Measure: Fraction of healthcare workers infected with SARS-CoV-2 Time: 90 daysDescription: To compare the infection rate of hospitalized patients versus healthcare workers
Measure: Fraction of healthcare workers with COVID-19 Time: 90 daysDescription: Tracing origins of infection in healthcare workers to distinguish between community versus hospital acquired.
Measure: Number of patients infected in the hospital Time: 90 daysDescription: To determine the T and B cell specific antibody repertoire in the course of a COVID-19 infection.
Measure: Development of SARS-CoV2 specific antibody repertoire Time: 18 monthsA prospective, controlled, randomized, multicenter study whose goal is to compare the efficacy of a chloroquine analog (GNS561), an anti PD-1 (nivolumab) and an anti-interleukine-6 receptor (tocilizumab) versus standard of care in patients with advanced or metastatic cancer who have Sars-CoV-2 infection not eligible to a resuscitation unit. According to their severity level at the time of enrolment, eligible patients will be randomized into 2 different cohorts: - COHORT 1 (mild symptoms or asymptomatic): GNS561 vs anti-PD1 vs standard of care (randomization ratio 1:1:1). - COHORT 2 (moderate/severe symptoms): GNS561 vs anti-IL6 vs standard of care (randomization ratio 1:1:1).
Description: 28-day survival rate, defined by the proportion of patients still alive 28 days after randomization. The 28-day survival rate will be described in each arm of each cohort.
Measure: 28-day survival rate Time: 28 days from randomizationDescription: Time to clinical improvement defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale (WHO-ISARIC) or live discharge from the hospital, whichever comes first.
Measure: Time to clinical improvement Time: 28 days from randomizationDescription: Clinical status will be assessed using a 7-point ordinal scale : 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 Time: Day 7, Day 14, Day 28Description: Mean change in clinical status from baseline will be assessed using a 7-point ordinal scale.
Measure: Mean change in clinical status from baseline to days Time: Day 7, Day 14, Day 28Description: Overall survival will be defined by the time from date of randomization until date of death, regardless of the cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
Measure: Overall survival Time: 3 months (i.e. at the the time of last patient last visit)Description: The length of stay in Intensive Care Unit (from the date of admission in the Unit to the date of discharge).
Measure: Length of stay in Intensive Care Unit Time: 3 months (i.e. at the the time of last patient last visit)Description: The duration of mechanical ventilation or high flow oxygen devices (from the date of intubation to the stop date of mechanical ventilation or high flow oxygen)
Measure: Duration of mechanical ventilation or high flow oxygen devices Time: 3 months (i.e. at the the time of last patient last visit)Description: The duration of hospitalization (from the date of hospitalization to the date of definitive discharge for live patients)
Measure: Duration of hospitalization Time: 3 months (i.e. at the the time of last patient last visit)Description: Changes from baseline in neutrophils count (G/L)
Measure: Biological parameters Time: 3 months (i.e. at the the time of last patient last visit)Description: Treatment-Emergent Adverse Events, Serious Adverse Events, Suspected Unexpected Serious Adverse Reactions, New Safety Issues described using the NCI-CTC AE classification v5. Number of participants with a discontinuation or temporary suspension of study drugs (for any reason).
Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 Time: 3 months (i.e. at the the time of last patient last visit)Description: Incremental Cost-Effectiveness Ratios (ICERs) expressed in cost per Life Year Gained.
Measure: Cost-Effectiveness Analyses (CEA) Time: 3 months (i.e. at the the time of last patient last visit)Description: Changes from baseline in lymphocytes count (G/L)
Measure: Biological parameters Time: 3 months (i.e. at the the time of last patient last visit)Description: Changes from baseline in platelets count (G/L)
Measure: Biological parameters Time: 3 months (i.e. at the the time of last patient last visit)Description: Changes from baseline in hemoglobin count (g/dL)
Measure: Biological parameters Time: 3 months (i.e. at the the time of last patient last visit)Description: Changes from baseline in CRP count (mg/L)
Measure: Biological parameters Time: 3 months (i.e. at the the time of last patient last visit)Description: Changes from baseline in pro-inflammatory cytokine (IL6)
Measure: Biological parameters Time: 3 months (i.e. at the the time of last patient last visit)This is a Phase II interventional study will test the efficacy of quintuple therapy (Hydroxychloroquine, Azithromycin, Vitamin C, Vitamin D, and Zinc) in the treatment of patients with COVID-19 infection).
Description: Number of days from COVID-19 diagnosis to recovery via RT-PCR
Measure: The rate of recovery of mild or moderate COVID-19 in patients using Quintuple Therapy Time: 12 weeksDescription: Reduction and/or progression of symptomatic days, reduction of symptom severity
Measure: Reduction or Progression of Symptomatic Days Time: 12 weeksDescription: Assess the symptom response to study therapy as measured by the survey in the EDC
Measure: Assess the safety of Quintuple Therapy Time: 12 weeksDescription: Pulse from baseline to 12 weeks
Measure: Assess the safety of Quintuple Therapy via pulse Time: 12 weeksDescription: Oxygen saturation from baseline to 12 weeks
Measure: Assess the safety of Quintuple Therapy via oxygen saturation Time: 12 weeksDescription: EKG response from baseline to 12 weeks
Measure: Assess the safety of Quintuple Therapy via EKG Time: 12 weeksDescription: Assess Adverse Events and Serious Adverse Events due to Quintuple Therapy
Measure: Assess Tolerability of Quintuple Therapy Time: 12 weeksHealthcare 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 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 weeksThis is a pragmatic, randomized, open-label, incomplete factorial with nested randomization clinical trial evaluating the efficacy and safety of two potential treatments for hospitalized patients with confirmed SARS-CoV-2 infection. Participants who are hospitalized and have a positive nucleic acid amplification test for SARS-CoV-2 will undergo an initial randomization in a 1:1 ratio to one of the following regimens: Arm 1: Standard of care alone Arm 2: Standard of care plus hydroxychloroquine Participants who meet eligibility criteria to receive azithromycin will undergo a second randomization in a 1:1 ratio to receive additional concurrent therapy. This will effectively result in four treatment groups: 1. Standard of care alone 2. Standard of care plus hydroxychloroquine 3. Standard of care plus azithromycin 4. Standard of care plus hydroxychloroquine plus azithromycin
Description: 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: World Health Organization (WHO) ordinal scale measured at 14 days after enrollment Time: Day 14Description: 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: WHO ordinal scale measured at 28 days after enrollment Time: Day 28In the current COVID-19 pandemic with coronavirus, SARS-COV2, the Danish Health Authorities recommend using facial masks in the health care system when handling patients presumed or proven to be infected with the virus. However, the use of facial masks outside the health care system is not recommended by the Danish Health Authorities. Here, Health Authorities in other countries have different recommendations for the use of facial masks. Challenges when using facial masks outside the health care system include wearing the mask consistently, an efficacy of the mask of app. 8 hours necessitating a change of mask throughout the day, and that it is not sufficiently tight enough to safely keep the virus out. Moreover, the eyes (mucous membrane) remain exposed. Compliance could also be another challenge. SARS-COV2 is assumed to primarily enter the body via the mouth through respiratory droplets - or possibly through inhalation of aerosol containing the virus. From the mouth the virus is assumed to spread to the airways and the gastro-intestinal tract. SARS-COV2 is also known to be transmitted via physical contact, helped along by the fact that the virus can survive on surfaces for at least 72 hours. Touching such a contaminated surface can transfer the virus to the mouth via the hand - and thus lead to infection of the person. Facial masks are expected to protect against viral infection in two ways; 1. By reducing the risk of getting the virus in via the mouth or nose via respiratory droplets or aerosol 2. By reducing the transfer from virus-contaminated hands to the mouth or nose Hypothesis The use of surgical facial masks outside the hospital will reduce the frequency of COVID-19 infection. All participants will follow authority recommendations and be randomized to either wear facial masks or not. The participants will be screened for antibodies at study start and study end. They will perform swab-test if they experience symptoms during the study as well as the end of study.
Description: Reduction in COVID-19 infection frequency
Measure: Reduction in COVID-19 infection frequency Time: 30 daysDescription: Number of participants testing positive in antibody screening at study start and study end, respectively
Measure: Antibody-screening Time: 30 daysThis 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 spread of novel Coronavirus (2019-nCoV) related infection (COVID-19) has led to many patient presentations in the emergency department for respiratory complaints, with many of these patients requiring ICU admission and ventilatory support. While COVID-19 patients have an increased need for supportive care, there is currently no specific treatment directed against 2019-nCoV. Nitric oxide inhalation has been used as a pulmonary vasodilator and has been found to have antiviral activity against other coronavirus strains. The primary aim of this study is to determine whether inhaled NO improves short term respiratory status, prevents future hospitalization, and improves the clinical course in patients diagnosed with COVID-19 specifically in the emergency department.
Description: Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to return to the ED with worsening symptoms
Measure: Rates of return visits to the ED Time: 28 daysDescription: Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to require hospitalization during their COVID-19 course
Measure: Inpatient hospitalizations required Time: 28 daysDescription: Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to require intubation during their COVID-19 course
Measure: Rates of intubation Time: 28 daysDescription: Difference within treatment and control groups with COVID-related symptoms/disease in their likelihood to die of any cause within 28 days of their initial ED visit
Measure: Rates of mortality Time: 28 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 hoursOur 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: ScreeningSince December 2019, a new agent, the SARS-Cov-2 coronavirus has been rapidly spreading from China to other countries causing an international outbreak of respiratory illnesses named COVID-19. In France, the first cases have been reported at the end of January with more than 60000 cases reported since then. A significant proportion (20-30%) of hospitalized COVID-19 patients will be admitted to intensive care unit. However, few data are available for this special population in France. We conduct a large observational cohort of ICU suspected or proven COVID-19 patients that will enable to describe the initial management of COVID 19 patients admitted to ICU and to identify factors correlated to clinical outcome.
Description: Mortality at day 28
Measure: Mortality at day 28 Time: day 28Description: severe complications (pulmonary embolism, acute kidney injury, myocarditis, cardiac arrest, liver failure, ventilator associated pneumonia) Yes / No
Measure: severe complications Time: up to day 28Description: Delay in imaging in hours
Measure: Imaging Time: day 1Description: delay in microbiological diagnosis in hours
Measure: Delay in Microbiological diagnosis Time: day 1Description: Antiviral therapy Yes / no
Measure: Antiviral therapy Time: up to day 28Description: Antibiotic therapy Yes / No
Measure: Antibiotic therapy Time: day 28Description: Covid-19 treatments Yes / No
Measure: Covid-19 treatments Time: up to day 28Description: number
Measure: Patients receiving renal replacement therapy Time: up to day 28Description: number
Measure: Patients receiving mechanical ventilation Time: up to day 28Description: Patient alive at day 28 : yes / No
Measure: Vital status Time: day 28The purpose of this research is to identify whether or not Angiotensin Receptor Blockers (ARB) can halt the progression to respiratory failure requiring transfer into the intensive care unit (ICU), as well as halt mechanical ventilation in subjects with mild to moderate hypoxia due to the corona virus that causes COVID-19. Based on previous animal studies, the researchers hypothesize that the addition of an ARB is beneficial in abating acute lung injury in subjects in early stages of SARS-CoV-2 viral induced hypoxia.
Description: Number of subjects requiring transfer into ICU for mechanical ventilation due to respiratory failure
Measure: Mechanical ventilation Time: from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 daysDescription: Number of subjects transferred from non-ICU bed to an ICU bed
Measure: ICU transfer Time: from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 daysDescription: Number of days requiring oxygen therapy
Measure: Oxygen therapy Time: from date of patient admission to date of patient discharge or date of death, whichever came first, assessed up to 45 daysThe 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 daysA 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)This is a multi-centre population-based follow-up study for all 504 patients with laboratory-confirmed COVID-19. This study establishes a standardized and structured clinical database to provide complete and multidimensional clinical diagnosis and treatment data of novel coronavirus pneumonia, which also support future epidemiological, infectious disease study and patients' prognosis, by collecting clinical data and the related data of patients with novel coronavirus pneumonia in Southern Zhejiang province.
Description: sum score of SF 36 form in each time frame
Measure: 36-Item Short Form Survey Instrument (SF-36) Time: one month, three month, six month and one year after discharge, minimum scoreDescription: laboratory result
Measure: Lymphocyte value Time: one month, three month, six month and one year after dischargeDescription: laboratory result
Measure: Neutrophil value Time: one month, three month, six month and one year after dischargeDescription: laboratory result
Measure: DDI value Time: one month, three month, six month and one year after dischargeDescription: collect the number of applying ACEIs/ARBs medication and calculate the proportion
Measure: the proportion of applying ACEIs/ARBs medication Time: from the date of hospital admission to the day of hospital dischargeDescription: clinical symptoms
Measure: number of clinical symptoms after hospital discharge Time: one month, three month, six month and one year after dischargeThe 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 daysIt appears interesting to use nivolumab in severe patients infected with SARS-CoV-2 requiring hospitalization in conventional unit or in ICU. This protocol CORIMUNO19-NIVO therefore, will evaluate the efficacy and safety of OPTIVO® (nivolumab) COVID-19 patients hospitalized in conventional unit. The purpose of this study is to show the efficacy of nivolumab in patients with COVID-19 in combination with standard treatments. A phase 2 randomized open trial will evaluate the efficacy and safety of optivo® (nivolumab) alone versus standard of care (SoC) in patients hospitalized in conventional units. Patients will be randomly allocated 1:1 to either nivolumab or SoC.
Description: the time required for clinical improvement, defined as the time elapsed between randomization and a two-point improvement on an ordinal scale with seven categories (WHO scale), or the discharge alive from hospital, whatever occurred first
Measure: Time to clinical improvement Time: day 14Description: according to CTC AE-4.03
Measure: Incidence of grade 3-4 adverse events Time: day 28Description: range, from 0 (healthy) to 10 (death)
Measure: World Health Organisation (WHO) progression scale Time: day 4, 7 and 14We will evaluate low-dose pyridostigmine as add-on therapy to best medical care in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and its related Coronavirus Disease 2019 (COVID-19) who require hospitalization. Our hypothesis is that, in comparison to the placebo, pyridostigmine will reduce in at least 10% a composite outcome [death; mechanical ventilation; >2 point-increase in the SOFA score) by day 28. We will also evaluate interleukin (IL)-6 kinetics during the first 14 days of in-hospital stay. It is estimated that 25-33% of patients hospitalized for COVID-19 are admitted to intensive care units (ICU) for severe hypoxemia. The reported mortality in those with severe disease ranges between 38% and 49%. So far, there is no pharmacological therapeutic (or else) strategy known to reduce morbidity and mortality in these patients. Mortality in COVID-19 appears to be mediated not necessarily by the direct effect of the infection, but by the disproportionate inflammatory response of the host. Pyridostigmine is an old drug that, by inhibiting acetylcholine-esterase, the enzymatic machinery that degrades acetylcholine (ACh), results in increased ACh bioavailability. ACh, in turn, ligates to nicotinic-alpha7 receptors in macrophages and T cells, resulting in reduced overactivation of these immune cells. In experimental murine sepsis, this family of drugs has resulted in reduced inflammation and mortality. Human evidence is scarce for severe inflammatory conditions. However, recent evidence from our group and others indicates that pyridostigmine has an immunomodulatory effect in people living with HIV, resulting in elevation of CD4+ T cell counts, decreased immune activation, and reduction in inflammatory mediators. Altogether, this suggests that ACh-esterase inhibitors may act as immunomodulators during viral infections, potentially reducing the inflammatory cascade (the so-called "cytokine storm") observed in critically ill COVID-19 patients. At the proposed dose (60mg/d), the rate of minor adverse events is less than 5% with no reported serious adverse effects. From that perspective, we consider that pyridostigmine can function as an immuno-modulator and reduce morbidity and mortality in COVID-19-stricken patients, with the added value of a safe pharmacological profile. Moreover, as an old drug, re-purposing it for a novel indication may be a simpler, more efficient approach than developing a novel one from the ground up.
Description: Composite of death, Need for mechanical ventilation, or an increase of 2 or more points in the SOFA score
Measure: Critical condition or death Time: 28 daysDescription: Kinetics of circulating IL-6
Measure: IL-6 Time: 14 days in-hospital, hospital discharge, or deathIn this study invetigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 80 patients will be enrolled and randomly assigned in a 1:1:1 ratio to three study arms and received clazakizumab at a dose of 12.5 mg, 25 mg or placebo. Based on interim analysis, the remaining 10 subjects at NYU will be randomly assigned to a 1:1 ratio to two arms that will receive clazakizumab at a dose of 25 mg or placebo. The NYU site will serve as the central data management site for other centers who undertake this protocol. Other sites will enroll patients based on the two arm 1:1 randomization. 60 patients at outside sites are expected to enroll.
Description: Number of patients who remain alive at time point.
Measure: Patient Survival Time: 28 daysDescription: Number of patients who remain alive at end of study.
Measure: Patient Survival Time: 60 daysThe Investigators propose to set up a preventive trial of infection in hospital workers at risk of coronavirus infection by comparing the rate of SARS-Cov-2 infection in a population of negative SARS-Cov-2 hospital workers receiving preventively azithromycin, hydroxychloroquine or a Placebo
Description: The number of hospital workers with a positive serology or a positive PCR within 40 days of follow-up.
Measure: To assess the impact of hydroxychloroquine and azithromycin on the prevention of SARS-CoV-2 contamination in hospital workers exposed to 40 days of treatment. Time: 3 monthsDescription: Clinical signs suggesting SARS-2 CoV infection confirmed by positive endonasal PCR
Measure: Reducing clinical episodes due to suspected SARS-2 CoV infection confirmed by PCR Time: 40 daysDescription: number of seroconversion by serology between Day 0 and Day 40.
Measure: Reducing seroconversion for SARS-CoV-2 without any clinical sign Time: 3 monthsDescription: number of cardiological severe adverse events assessed (ECG abnormalities : widening QT, ventricular arythmia, and cardiac arrests), other serious adverse events including hospitalizations, and deaths
Measure: Evaluation of drug tolerance in the study Time: 40 daysDescription: Number of work stoppages over the period
Measure: Evaluation on work stopping of hospital workers Time: 40 daysDescription: Plasmatic concentrations of treatments
Measure: Observance of treatment measured by plasmatic concentrations of hydroxychloroquine or azythromycine Time: 40 daysDescription: number of cardiac events, especialy ECG abnormalities (widening QT) due to treatments
Measure: Incidence of cardiologic events Time: 40 daysThis is a phase 2b prospective, randomized, single-blind, controlled trial of two weekly subcutaneous injections of lambda interferon alfa-1a versus placebo for prevention of SARS-CoV-2 infection in non-hospitalized participants at high risk for infection due to household exposure to an individual with coronavirus disease (COVID-19). The study will also evaluate the regimens participants with asymptomatic SARS-CoV-2 infection detected at study entry. All participants will be followed for up to 12 weeks.
Description: No evidence of SARS-CoV-2 infection at or before study day 28
Measure: Proportion of participants with no evidence of SARS-CoV-2 infection Time: Up to 28 daysDescription: Resolution of SARS-CoV-2 infection in the upper respiratory tract
Measure: Time (days) to no detection of SARS-CoV-2 in two upper respiratory samples Time: Up to 14 daysEvaluation of the efficacy and safety of Danoprevir sodium tablet combined with ritonavir for SARS-CoV-2 infected patients.
Description: Defined as SPO2≤ 93% without oxygen supplementation, PaO2/FiO2 ≤ 300mmHg or a respiratory rate ≥30 breaths per min without supplemental oxygen min without supplemental oxygen
Measure: Rate of composite adverse outcomes Time: Within 10 days after administrationDescription: Clinical recovery was defined as 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 ≥ 30 breaths per min without supplemental oxygen).
Measure: Time to recovery Time: Within 10 days after administrationTranslational, prospective / retrospective, non-profit, non-pharmacological study, with cohort characteristics. The study consists of two parts: the first to study epidemiological aspects of the spread of the disease and the second one to identify infection-related genetic factors.
Description: Investigate the epidemiology of the infection in an asymptomatic population including both healthy individuals at high risk of infection and oncological patients by assessing the seroprevalence of IgG and IgM antibodies against the SARS-CoV-2
Measure: epidemiology Time: 12 monthsDescription: IgG and IgM antibodies evaluation over time
Measure: Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies evaluation Time: 12 monthsDescription: Make a comparison between different serological investigation methods and rapid molecular methods becoming available
Measure: methods comparison Time: 24 monthsDescription: To evaluate correlation between biochemical and coagulative factors with SARS-CoV-2 positivity
Measure: correlation between biochemical and coagulative factors with SARS-CoV-2 positivity. Time: 24 monthsDescription: Building a phylogenetic map of an epidemic Italian macro-region
Measure: phylogenetic map Time: 24 monthsDescription: Evaluate the spectrum of possible interactions between the virus and host cells, considering their genetic variability / instability in patients diagnosed with COVID-19
Measure: interactions between the virus and host cells Time: 24 monthsIntensive action has been taken around the globe to fight the corona virus SARS-COV-2 (COVID-19) pandemia. Clinical symptoms of the infection appear to be variable, from basically asymptomatic infections and mild, flu-like symptoms up to severe respiratory insufficiency, requiring mechanical ventilation at the intensive care unit, and death. Broad testing for COVID-19 infection has been proven difficult in clinical practice and hampered by limited resources. Urgently needed epidemiological data on the rate of silent, asymptomatic infections in the population and the percentage of individuals that have already developed immunity are still missing. Within this study we therefore plan to (i) determine the proportion of asymptomatic COVID-19 virus carriers in (a) German Cancer Research Center (DKFZ) employees, who work and are present at the center during the time of extended minimum operation and (b) in all DKFZ employees before onboarding when extended minimum operation has been terminated. We plan to (ii) develop a high-throughput assay for COVID-19 testing as well as (iii) a serum-based COVID-19 antibody assay. Finally, we will (iv) analyze for a possible correlation between oral microbiome and COVID-19 infection status.
The purpose of the study is to evaluate an effectiveness of the drug Dalargin for the prevention and treatment of severe pulmonary complications symptoms associated with severe and critical coronavirus infection cases (SARS COVID19, expanded as Severe acute respiratory syndrome Cоrona Virus Disease 2019 ). Test drug that will be administered to patients are: - Dalargin, solution for inhalation administration, - Dalargin, solution for intravenous and intramuscular administration.
Description: Estimated by Polymerase chain reaction (PCR)
Measure: The change of viral load in patients with SARS-COVID-19. Time: Upon patient inclusion in the study, after 96 hours and on the 10day;Description: Assessed through the entire patient participation in the study
Measure: The frequency of development of Acute Respiratory Distress Syndrome (ADRS) Time: up to 8 monthsDescription: The number of days a patient is hospitalized
Measure: Duration of hospitalization Time: through study completion, an average of 8 monthsDescription: Early mortality from all causes will be estimated
Measure: The frequency of early mortality Time: up to 30 daysDescription: Late mortality from all causes will be estimated
Measure: The frequency of late mortality Time: up to 90 daysDescription: Clinical status at the time of completion of participation in the study will be estimated based upon the following criteria: Death; Hospitalization is extended, on invasive mechanical ventilation of the lungs with extracorporeal membrane oxygenation; Hospitalization extended, on non-invasive ventilation; Hospitalization is extended, needs additional oxygen; Hospitalization is extended, additional oxygen is not required; Discharged.
Measure: Clinical status at the time of completion of participation in the study Time: through study completion, an average of 8 monthsThe overall objective of the study is to determine the therapeutic effect and tolerance of Eculizumab in patients with moderate, severe pneumonia or critical pneumonia associated with Coronavirus disease 2019 (COVID-19). Eculizumab is a terminal complement inhibitor that has been investigated for more than 10 years in numerous complement-mediated diseases. The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization will occur prior to offering Eculizumab administration to patients enrolled in the CORIMUNO-19 cohort. Eculizumab 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 Eculizumab will receive standard of care. Outcomes of Eculizumab-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 intubation, events considered are intubation or death
Measure: Survival without needs of intubation at day 14 Time: 14 daysDescription: Change in organ failure at day 3, defined by the relative variation in Sequential Organ Failure Assessment score
Measure: Change in organ failure at day 3 Time: 3 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: Intubation free survival at day 14 Time: Day 14Description: 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 days 4, 7 and 14 Time: 4, 7 and 14 daysDescription: Overall survival
Measure: Survival at 14, 28 and 90 days Time: 14, 28 and 90 daysDescription: Time between inclusion and hospital discharge
Measure: Time to discharge Time: 90 daysDescription: Time between inclusion and oxygen supply independency
Measure: Time to oxygen supply independency Time: 90 daysDescription: Time between inclusion and negative viral excretion
Measure: Time to negative viral excretion Time: 90 daysDescription: Incidence of secondary infections (acquired pneumonia)
Measure: Incidence of secondary infections Time: 90 daysDescription: Vasopressor-free survival
Measure: Vasopressor-free survival Time: 90 daysDescription: Ventilator-free survival
Measure: Ventilator-free survival Time: 90 daysDescription: Number of ventilator-free days alive up to day 28
Measure: 28-day ventilator-free days Time: 28 daysDescription: Incidence of dialysis (renal replacement therapy)
Measure: Incidence of dialysis Time: 90 daysDescription: PaO2/FiO2 ratio
Measure: PaO2/FiO2 ratio Time: days 4, 7, 14Description: Number of patients with arterial blood pH of <7.25, with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours
Measure: Rate of respiratory acidosis at day 4 Time: 4 daysDescription: Time to ICU discharge
Measure: Time to ICU discharge Time: 90 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 monthsThe goal of the research is to assess candidate COVID-19 rapid (5-15 min) antibody tests in order to judge their clinical accuracy compared to Centers for Disease Control (CDC)-recommended molecular genetic testing and clinical diagnosis. Second, it is our goal to determine if self-testing assisted by a mobile device camera acquisition software and telemedicine clinical/technical support (virtual point-of-care) improves the ease of use and interpretation of the tests, thus making self-testing comparable in accuracy and safety to testing in a clinical setting. The overall purpose of the study is to dramatically increase the capacity of COVID-19 testing by establishing the safety, ease-of-use and validity of finger-stick capillary blood self-testing assisted by mobile device imaging and telemedicine remote support.
Description: Accuracy refers to the amount of agreement between the results of the antibody-based rapid test and the results of a PCR-based reference test
Measure: Clinical accuracy of the antibody-based rapid tests compared to PCR-based test result Time: 1 yearDescription: Accuracy refers to the amount of agreement between the results of the antibody-based rapid test and a clinical diagnosis of COVID-19
Measure: Clinical accuracy of the rapid tests based on Clinical diagnosis Time: 1 yearDescription: Clinical accuracy of the subject's visual interpretation of the test result vs image analysis from clinician
Measure: Self-test interpretation of result vs expert clinical image interpretation of result Time: 1 yearDescription: Subjects will complete a survey to rate the testing procedure for ease of use and convenience. The survey will ask subjects to rate the ease of use on a scale from 1 (easiest procedure to complete and understand) to 10 (most complicated and confusing procedure)
Measure: Ease of self-testing procedure Time: 1 yearThe main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo.
The current sars-cov-2 epidemic is responsible for severe respiratory infections leading to end-of-life situations. Dexmedetomidine may be indicated in mild to moderate sedation in palliative patients, due to its pharmacological characteristics. The hypothesis of this study is that Dexmedetomidine would allow effective and safe light sedation in patients with respiratory failure in palliative situations suffering from Covid-19 infection.
Description: Number of days of mild to moderate sedation induced by dexmedetomidine until death or change of molecule.
Measure: Efficacy of mild to moderate palliative sedation induced by Dexmedetomidine. Time: Day 30Description: Overall survival time in days from inclusion.
Measure: Overall survival of patients on Dexmedetomidine Time: Day 30Description: The daily effectiveness of Dexmedetomidine on pain assessed by the NCS-R scale (Nociception Coma Scale) : the score is between 0 and 9.
Measure: Daily analgesic effect of Dexmedetomidine Time: Day 30Description: Number of the various sedative molecules used in the subjects of the study in addition to Dexmedetomidine.
Measure: Other sedative pharmacological agents Time: Day 30Description: Daily dosage measurement in ug / kg / h of Dexmedetomidine necessary to obtain light to moderate sedation
Measure: Average dosage required for Dexmedetomidine to achieve mild to moderate sedation Time: Day 30COVID-19 ( known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has a highly polymorphic clinical presentation, ranging from pauci-symptomatic infection to severe, potentially complicated forms with acute respiratory distress syndrome or multisystemic organs failure. The picture may be initially severe, or it may progress in two stages, with worsening 7 to 10 days after the first symptoms with an overall case-fatality rate of 3 to 4%. Its management is essentially symptomatic, as no antiviral treatment has so far demonstrated a clinical benefit in this condition. In such a context, healthcare professionals assigned to COVID units will be faced with a heavy workload and emotional burden that could lead to psychological suffering or even burnout and its consequences. We would therefore like to describe, using validated tools, the emotional evolution of the care workers at the Limoges University Hospital and the Esquirol University Hospital faced with this new pandemic infection. An initial and end-of-study evaluation of the caregivers will be carried out concerning their anxiety and depressive state, their personal capacity for resilience and their degree of empathy
Description: Assessing the anxiety of health professionals using Anxiety Disorder Assessment (GAD-7) scale. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.
Measure: anxiety Time: 7 days,Description: Assessing the anxiety of health professionals using Anxiety Disorder Assessment (GAD-7) scale. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.
Measure: anxiety Time: 15 days,Description: Assessing the anxiety of health professionals using Anxiety Disorder Assessment (GAD-7) scale. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.
Measure: anxiety Time: 1 monthDescription: Assessing the anxiety of health professionals using Anxiety Disorder Assessment (GAD-7) scale. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.
Measure: anxiety Time: 3 monthThe AGMT_COVID-19 Registry is designed as multicenter observational cohort of patients, that are tested positive for SARS-CoV-2. Data will be collected from all sites in Austria willing to participate. Due to the non-interventional nature of the AGMT_COVID-19 registry, only routine data, which has already been recorded in the patient's medical chart, is transferred to the eCRF.
Description: Due to the non-interventional nature of the AGMT_COVID-19 registry, only routine data, which has already been recorded in the patient's medical chart, is transferred to the eCRF. Treatment indication, the decision to offer treatment, treatment choice, dose, schedule and dose reductions/escalations, and response assessments shall be exclusively based on the risk/benefit estimation of the treating physician.
Measure: Documentation of natural course and the therapeutic landscape of patients with COVID-19. Time: 2 yearsThis is a retrospective/prospective, cohort, non-interventional observational study. This means that all patients with documented COVID and HM diagnosed between February 2020 and study initiation will compose the retrospective part, while those diagnosed after study approval will enter prospective part. The total duration of the study will be 12 months. The study population will must be older than 18 years of age with HM and SARS-CoV-2 infection. All patients with documented SARS-CoV-2 infection (COVID) and history or active hematological malignancies, who refer to any Hematological Unit will be included.
Description: The percentage of HM patients with COVID-19 who died.
Measure: To evaluate mortality. Time: At 2 months from study initiationDescription: We will assess the correlation between some biochemical parameters at diagnosis of COVID (i.e. hemoglobin, platelets, lymphocytes, clotting tests, CRP), each on the basis of its specific unit of measure, and mortality.
Measure: To evaluate potential predictive biochemical parameters of mortality. Time: At 2 months from study initiationDescription: We will assess the correlation between HM-related parameters at diagnosis of COVID [i.e. disease type (leukemia, lymphomas, myeloma), disease status (remission / stable / progression), therapy status (on / off therapy)] and mortality.
Measure: To evaluate potential predictive HM-related parameters of mortality. Time: At 2 months from study initiationDescription: We will assess the correlation between COVID severity [mild (non-pneumonia and mild pneumonia), severe (dyspnea, respiratory frequency ≥ 30/min, SpO2 ≤ 93%, PaO2/FiO2 < 300 and/or lung infiltrates > 50%) and critical (respiratory failure, septic shock, and/or multiple organ disfunction or failure)] and mortality
Measure: To evaluate COVID severity as predictive parameter of mortality. Time: At 2 months from study initiationDescription: Description of the different types of hematological malignancies (WHO criteria) in patients with SARS-CoV-2 infection. All aggregated data will be stratified on the basis of COVID severity: mild (non-pneumonia and mild pneumonia), severe (dyspnea, respiratory frequency ≥ 30/min, SpO2 ≤ 93%, PaO2/FiO2 < 300 and/or lung infiltrates > 50%) and critical disease (respiratory failure, septic shock, and/or multiple organ disfunction or failure)
Measure: Epidemiology of patients with HM infected by SARS-CoV-2with any spectrum of illness severity Time: At 6 months from study initiationDescription: Characterization of clinical and biochemical profile of patients with SARS-CoV-2 positivity.
Measure: Definition of complete clinical picture of COVID-19 in HM Time: At 2 months from study initiationDescription: Assessment of HM status post SARS-CoV-2 infection stratified as no implication, loss of response, progression of the hematological disease.
Measure: Evolution of HM Time: At 2 months from study initiationDescription: Percentage of HM patients being admitted to ICU requiring mechanical ventilation, or death stratified per disease type, status, per off-therapy/on-therapy, per type of therapy (chemo, immunotherapy, cell therapy, stem cell transplant).
Measure: To evaluate admission to ICU requiring mechanical ventilation or death per characteristics Time: At 2 months from study initiationThere is an urgent need to evaluate interventions that can prevent the infection with SARS-CoV 2 of healthcare workers at risk. Melatonin is an inexpensive and safe product with protective effect in both bacterial and viral infections likely due to its anti-inflammatory and anti-oxidative effects. This randomized controlled trial seeks to evaluate is efficacy as a prophylaxis in healthcare workers exposed to the virus in their clinical practice.
Description: Number of confirmed (positive CRP) symptomatic infections in each treatment group
Measure: SARS-CoV 2 infection rate Time: up to 12 weeksCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the disease progresses, a series of acute complications tend to develop in multiple organs. Beyond the supportive care, no specific treatment has been established for COVID-19. The effectiveness, both short-term and long-term, of some promising antivirals, such as the hydroxychloroquine combination with azithromycin, needs to be evaluated. This study aims to investigate the predictive role of cardiac biomarkers and pulmonary symptoms for late complications of COVID-19 coronavirus infection on the heart and lung in patients treated with the hydroxychloroquine / azithromycin combination therapy. Thus, COVID-19 coronavirus patients undergoing hydroxychloroquine / azithromycin combination therapy will be compared to patients not undergoing this therapy. The comparison will be made by the analysis of the relationships between (1) levels of ultrasensitive cardiac troponins collected at the beginning of the infection and cardiac magnetic resonance data in the 3rd and 12th months of troponin collection and (2) findings CT scans and the results of the ergospirometers tests performed in those same periods. It is expected to demonstrate that: (1) cardiac troponin and lung tomographic findings can predict late complications of COVID-19 coronavirus infection in the heart and lung, assessed by cardiac magnetic resonance and ergospirometers one year after the beginning of the infection, and (2) hydroxychloroquine / azithromycin combined therapy can abolish the onset of these complications late. Furthermore, the results may point to the need for more rigorous monitoring of cardiologists and pulmonologists of these patients, due to the risk of hemodynamic complications, arrhythmogenic and respiratory.
Description: presence of fibrosis on cardiac resonance and / or decreased functional capacity on ergospirometry
Measure: Fibrosis Time: 12 monthsDescription: Decreased functional capacity on ergospirometers
Measure: Ergospirometers Time: 12 monthesThe Nancy Cov-H-AKI: study is a prospective, non-randomized, monocenter study performed in patients hospitalised for either the severe or the critical form of Covid-19. The main objective of the Nancy Cov-H-AKI study is to evaluate the association of variations (from inclusion to 72H post-inclusion) of 5 blood-based cardio-vascular-renal biomarkers selected a priori, cardiac (NT-proBNP), coagulation (D-dimers), related to the renin angiotensin aldosterone system (ACE2) and renal (Penkid, and NGAL) with the appearance of acute kidney injury KDIGO grade 1 or higher OR cardiac injury in patients hospitalised for either the severe or the critical form of Covid-19
Description: Composite endpoint : Worsening of renal function by at least KDIGO grade 1 criteria from inclusion visit OR troponin greater than 99th percentile during hospitalization for Covid-19 infection (with Outcome 2).
Measure: Worsening of renal function by at least KDIGO grade 1 during hospitalization for Covid-19 infection Time: From inclusion to hospital discharge, an average of 21 daysDescription: Composite endpoint : Worsening of renal function by at least KDIGO grade 1 criteria from inclusion visit OR troponin greater than 99th percentile during hospitalization for Covid-19 infection (with Outcome 1)
Measure: Troponin greater than 99th percentile during hospitalization for Covid-19 infection Time: From inclusion to hospital discharge, an average of 21 daysDescription: Composite endpoint : AKI KDIGO grade 1 or higher or Elevation of troponin> 99th percentile in hospitalisation (approach with AND without a priori) ((with Outcome 3 )
Measure: AKI KDIGO grade 1 or higher in hospitalisation (approach with AND without a priori) Time: From inclusion to hospital discharge, an average of 21 daysDescription: Composite endpoint : AKI KDIGO grade 1 or higher or Elevation of troponin> 99th percentile in hospitalisation (approach with AND without a priori) (with Outcome 3)
Measure: Elevation of troponin> 99th percentile in hospitalisation (approach with AND without a priori) Time: From inclusion to hospital discharge, an average of 21 daysDescription: AKI KDIGO grade 1 in hospitalisation
Measure: AKI KDIGO grade 1 or higher Time: From inclusion to hospital discharge, an average of 21 daysDescription: Association with troponin elevation >99th percentile during hospitalisation
Measure: Association with troponin elevation >99th Time: From inclusion to hospital discharge, an average of 21 daysDescription: Association with elevation of serum creatinine >30% during hospitalisation
Measure: Association with elevation of serum creatinine >30% Time: From inclusion to hospital discharge, an average of 21 daysDescription: With the onset of chronic renal failure (eDFG <60 ml / min / 1.73m2) three months after discharge from hospital
Measure: With the onset of chronic renal failure (eDFG <60 ml / min / 1.73m2) Time: 3 months after discharge from hospitalDescription: Composite outcome : the occurrence of cardiovascular events (stroke, myocardial infarction, hospitalisation for heart failure, cardiovascular death) and death from any cause during hospitalisation and three months after discharge from hospital
Measure: The occurrence of cardiovascular events (stroke, myocardial infarction, hospitalisation for heart failure, cardiovascular death) during hospitalisation and three months after discharge from hospital Time: From inclusion to three months after discharge from hospitalDescription: Composite outcome : the occurrence of cardiovascular events (stroke, myocardial infarction, hospitalisation for heart failure, cardiovascular death) and death from any cause during hospitalisation and three months after discharge from hospital
Measure: The occurrence of death from any cause during hospitalisation and three months after discharge from hospital Time: From inclusion to three months after discharge from hospitalContext: On March 11, the World Health Organization (WHO) announced the current corona virus disease 2019 (COVID-19) outbreak as a pandemic. The first laboratory-confirmed case of COVID-19 in Austria was announced on February 27, 2020. Since then, the incidence of infection follows a gradual increase. Measurements taken by the Austrian government include travel restrictions, closing of national borders, social distancing, a mandatory use of facemasks in public, and closing of stores and restaurants. The underlying aim of those imposed restrictions is to contain the viral transmission and to slow spreading of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: The aims of this study are to determine i) how many employees in Austrian trauma hospitals and rehabilitation facilities have virus specific IgG and IgM antibodies against SARS-CoV-2, ii) how many are active virus carriers (symptomatic and asymptomatic), iii) how many employees are in their incubation period during the study period, and iv) to calculate the SARS-CoV-2 prevalence together with a specific occupation associated infection risk within the different specifications of health care workers. Study Design: Open uncontrolled observational cross-sectional study. Setting/Participants: A total of 4000 employees in 11 Austrian trauma hospitals and rehabilitation facilities of the Austrian Social Insurance for Occupational Risks (AUVA) will be invited to participate in the study. Study Interventions and Measures: An antibody test for SARS-CoV-2 specific IgG and IgM antibodies, and a RT-PCR test based on oropharyngeal swab samples, as well as laboratory-based antibody tests using ELISA, will be implemented to ensure protection and preservation of health in hospital staff and are not part of the study. The tests will be conducted twice, with approximately two weeks in between testing. The results of the tests will be used for statistical analysis in this study together with a questionnaire including questions related to personal health, traveling activities, living situation, as well as inquiries of symptoms and comorbidities.
Description: To determine how many employees in Austrian trauma hospitals and rehabilitation facilities have already virus specific IgG and IgM antibodies against SARS-CoV-2.
Measure: Antibody status in HCW Time: 4 monthsDescription: To determine how many are actively infected with or without showing symptoms.
Measure: Active virus carriers in HCW Time: 4 monthsDescription: To determine how many employees are in their incubation period during study time.
Measure: Incubation time Time: 4 monthsDescription: To evaluate the "background incidence rate" of COVID-19 to calculate the SARS-CoV-2 prevalence in a defined cohort of the Austrian population.
Measure: Background incidence rate Time: 4 monthsDescription: To calculate a specific occupation associated infection risk within the different specifications of health care workers amongst AUVA employees.
Measure: Occupation associated infection risk Time: 4 monthsTo assess the seroprevalence of SARS-CoV-2 IgG in Health care workers in three University Hospitals
Description: health care workers who have positive IGg in seum
Measure: Number of IGg seropositive health care workers Time: single measurement from each person collected over 2 monthsDescription: to know positive IGg persons and IGg negative persons to understand risk factors
Measure: Differentiation between low risk and high risk HCWs Time: 2 months through out duration of studyThis is a Phase II study. This research study is being conducted to use convalescent donor plasma in seriously ill patients who have COVID-19.
Description: Overall mortality within 60 days
Measure: Overall Mortality within 60 days Time: sixty days from infusion of plasmaDescription: length of admission for COVID
Measure: Length of ICU stay during current admission for COVID Time: Length of admission for COVID through study follow-up period, an average of 60 daysA novel human coronavirus, named SevereAcute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), emerged in China, in late 2019, and is now spreading quickly causing a pandemic. It is usually responsible for a mild infectious syndrome, but patients can also develop pneumonia, acute respiratory failure and other serious complications. To date, very little and controversial literature is available on the impact of SARS-CoV-2 infection on pregnancy, and the potential risk of vertical transmission. Therefore, the first part of the study, will evaluate the proportion of pregnant woman infected by SARS-CoV-2 during pregnancy over the next six months by performing SARS-CoV-2 serology during pregnancy and at delivery . This information will be correlated to pregnancy and neonatal outcome. The second part of the study 2 will collect sera from several mandatory screening that are kept for one year. Those will be used for assessing the time of the seroconversion and variations of susceptibility to infection with gestational age as well as the impact of social distancing measures. Concerning neonates born to mothers with documented SARS-CoV-2 infection during pregnancy, only few cases of congenital infections were recently reported because of pneumonia related to SARS-CoV-2 infection and/or positive IgM at birth. It remains unclear whether neonatal infection can follow transplacental transmission of SARS-CoV-2 during pregnancy and/or through early per- and postnatal exposure, including breast-feeding. In order to investigate these hypotheses, the third part of the study will perform, SARS-CoV-2 PCR tests in a variety of samples collected from infected-mother (symptomatic during the pregnancy and PCR confirmed) and child pairs, at delivery and in the postpartum period.
Description: Number of women who are positive for SARS-CoV-2
Measure: Seroprevalence or Number of women who are positive for SARS-CoV-2 in parturient woman Time: at deliveryDescription: Correlation between exposure to the virus (confirmed by serology) and its impact on pregnancy and its outcome : Pregnancy outcome, maternal or neonatal complications
Measure: Consequences of SARS-CoV-2 infection in pregnant women and their newborns : Pregnancy outcome, maternal or neonatal complications Time: 2 months after deliveryDescription: Presence of virus (objectified by PCR) in the different biological compartments tested :In the mother: vaginal, anal, amniotic fluid and in the newborn: nasopharyngeal swabs, gastric aspiration, anal swab.
Measure: Assessment of the vertical transmission of SARS-CoV-2 and the possible routes of this transmission in women who are positive for SARS-CoV-2 during pregnancy Time: at deliveryDescription: Presence of virus (objectified by PCR) in the different biological compartments tested :In the mother: milk and stool samples and in the newborn: nasopharyngeal swabs, urine and stool.
Measure: Assessment of the vertical transmission of SARS-CoV-2 and the possible routes of this transmission in women who are positive for SARS-CoV-2 during pregnancy Time: 5 days after deliveryDescription: Evaluation of gestational age at SARSCoV-2 infection by performing serology on monthly collected serum samples (samples collected for routine management of pregnancy).
Measure: Assessment of susceptibility to infection during the 3 trimesters of pregnancy Time: 5 days after deliveryDescription: Study of the methods of confinement by investigation
Measure: Evaluation of the confinement on the risk of exposure to the virus during pregnancy . Time: 5 days after deliveryDescription: A biobank will be carried out, including the collection of several biological samples at the time of maternal SARS-CoV-2 infection, at delivery and in the postpartum period in the parturient and her newborn
Measure: collection of biological samples for new investigations in women who are positive for SARS-CoV-2 during pregnancy. Time: 5 days after deliveryDescription: Risk factors in uninfected women
Measure: Assessment of the rate of SARS-CoV-2 infection in pregnant women the risk factors for the disease. Time: at deliveryDescription: Risk factors in infected and symptomatic women.
Measure: Assessment of the rate of SARS-CoV-2 infection in pregnant women the risk factors for the disease. Time: at deliveryDescription: risk factors in newborns
Measure: Assessment of the rate of SARS-CoV-2 infection in newborns and the risk factors for the disease. Time: at deliveryThis is an observational study, meaning that no interventions is tested, to determine incidence of SARS-CoV-2 infection and COVID-19 in different clinical sites in Brazil in several age groups. The study aims to assess baseline number of infected participants and perform a follow-up along two years to determine the new cases occurring among participants during the period. All participants will collect blood samples to get more details on the immune response.
Description: Number of cases with serological/virological diagnosis for SARS-Co-2 infection
Measure: Incidence of SARS-CoV-2 infection Time: 24 monthsDescription: Number of cases of symptomatic SARS-CoV-2 infection
Measure: Incidence of COVID-19 Time: 24 monthsDescription: Number of cases of hospitalization due to symptomatic SARS-Co-2 infection
Measure: Incidence of hospitalization due to COVID-19 Time: 24 yearsDescription: Level of neutralizing antibodies in participants with SARS-Co-2 infection
Measure: Level of neutralizing antibodies Time: 24 monthsDescription: Positive serology for SARS-Co-2 infection at baseline
Measure: Previous SARS-CoV-2 infection Time: 6 monthsDescription: Number of a new SARS-CoV-2 infection in an individual with a proven previous infection
Measure: Incidence of SARS-CoV-2 reinfection Time: 24 monthsDescription: Number of COVID-19 cases requiring mechanical ventilation
Measure: Incidence of COVID-19 cases requiring mechanical ventilation Time: 24 monthsDescription: Number of deaths due to COVID-19
Measure: Incidence of deaths due to COVID-19 Time: 24 monthsDescription: Number and description of sequels attributed to COVID-19
Measure: Incidence of sequels after COVID-19 Time: 24 monthsStudy of the cellular immune response during the SARS-CoV-2 infection and identify cytokinic profiles in caregivers exposed to the virus with asymptomatic forms of COVID19, patients with an asymptomatic form followed in ambulatory care and patients hospitalized in the infectious disease department or in resuscitation at the CHU de Nice COVID-19 according to their clinical symptomatology and the kinetics of clinical aggravation using functional tests evaluating the Th1 type immune response. The project is divided into a clinical component comprising the study of the immune response in different populations and a cellular component focusing on the in vitro study of different immunomodulating treatments on their ability to induce an anti-viral Th1
Description: Peripheral T lymphocytes will be stimulated with an anti-CD3 for 16-24h. The Level of IFN-gamma (pg/mL) will be defined using an automated ELISA test (Protein Simple) on the stimulated and non-stimulated plasma.
Measure: Level of IFN-gamma after a non-specific stimulation of T lymphocytes Time: 6 monthsInflammation and abnormalities in laboratory coagulation tests are inseparably tied. For example, coagulation abnormalities are nearly universal in septic patients. Coagulation disorders have also been reported in many patients with severe courses of Coronavirus disease 2019 (Covid-19). But it is difficult to assess these changes. Global coagulation tests have been shown to incorrectly assess in vivo coagulation in patients admitted to intensive care units. But other tests are available. Thrombin generation assay (TGA) is a laboratory test which allows the assessment of an individual's potential to generate thrombin. But also in conventional TGA the protein C system is hardly activated because of the absence of endothelial cells (containing natural thrombomodulin) in the plasma sample. Therefore the investigators add recombinant human thrombomodulin to a conventional TGA. Thereby the investigators hope to be able to depict in vivo coagulation more closely than global coagulation tests do.
Description: nM;
Measure: ETP (AUC) without rhThrombomodulin (rhTM) Time: 6 monthsDescription: nM;
Measure: ETP (AUC) with rhThrombomodulin (rhTM) Time: 6 monthsDescription: Ratio of endogenous thrombin potential (ETP) with rhTM to ETP without rhTM
Measure: ETP-ratio Time: 6 monthsDescription: Comparison of ETP-ratios from ICU patients and ETP-ratios from citrated plasma samples from healthy donors
Measure: ETP-Normalisation Time: 6 monthsThe COVID-19 emerging disease due to a novel coronavirus (SARS-CoV-2), started in Wuhan, China, last December, 2019. In the past three months, the virus has spread rapidly worldwide to reach the pandemic threshold. Research has since been carried out and is intensifying in order to describe the clinical characteristics of infected patients, to identify the prognostic factors of acute respiratory distress syndrome [ARDS] and the death; and to assess the effectiveness of new antivirals and therapeutic strategies to treat COVID-19. Treatments currently being investigated include: - Potentially effective treatments: (hydroxy)chloroquine, Remdesivir, Lopinavir, Ritonavir +/- IFN-ß-1a (currently evaluated in the European discovery trial), methylprednisolone in patients with ARDS; - Potentially harmful treatments: antihypertensives such as converting enzyme inhibitors and angiotensin receptor antagonists. We made the hypothesis that (1) patients receiving ARBs or ACEi's have a higher risk to present a serious COVID-19 infection disease and (2) patients receiving synthetic AMD (e.g. HCQ and CQ) have a lower risk to present a serious covid19 infection disease. Using data from the French insurance health database (SNDS) and hospital discharge database (PMSI), our objectives are - Main objective: To assess the risk of moderate to serious COVID-19 infections in patients using synthetic anti-malarial drugs (AMD) or anti-hypertensive drugs (Angiotensin receptor-blocking/Angiotensin-converting-enzyme inhibitors). - Secondary objective : To examine the risk of moderate to serious COVID-19 infections according of age, sex, co-morbidities, level of exposure of AMD, geographical locations and underlying comorbidities. This in order to: - To prevent moderate to serious COVID-19 infections in at-risk population (diabetes, elderly, respiratory failure population) using synthetic AMD. - To prevent moderate to serious COVID-19 infections in at-risk population stopping angiotensin receptor-blocking and angiotensin-converting-enzyme inhibitors.
Description: Participants as those with the emergency ICD-10 (international classification of diseases, 10th revision) code of U07.1 which was assigned to the disease diagnosis of COVID-19.
Measure: Identification of serious COVID-19 infections Time: From 2020/01/01 to 2020/06/30This trial will estimate the efficacy and tolerance of several experimental treatments to prevent hospitalization or death in outpatients aged 65 years or above with Symptomatic SARS-CoV-2 Infection (COVID-19).
Description: Proportion of participants with an occurrence of death
Measure: Death Time: From inclusion (day0) to day 14Description: Proportion of deaths, overall and by cause, in each group
Measure: Death and causes of death Time: From inclusion (day0) to day 28Description: Evolution of Haematological markers in each group : Complete Blood Count, prothrombin level, INR
Measure: Haematological markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of Biochemical markers in each group : ferritin, serum creatinine, urea, sodium, potassium, chlorine, calcium, magnesium, albumin, bicarbonates / tCO2, LDH, CPK, ASAT, ALAT, uricemia
Measure: Biochemical markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of Inflammatory markers in each group : PCT, CRP
Measure: Inflammatory markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Evolution of immunological markers in each group : B ans T Cells phenotypic profiles
Measure: Immunological markers evolution Time: from inclusion (day 0) to day 7 and day 14Description: Number and proportion of grade 1,2,3,4 adverse events in each group
Measure: Adverse events Time: from inclusion (day 0) to day 14Description: Number and proportion of grade 1,2,3,4 adverse events in each group
Measure: Adverse reactions Time: from inclusion (day 0) to day 14Description: Plasma concentration of the study drugs at D7
Measure: Plasma concentration Time: day 7Description: Acceptability of the treatment by participant will be assessed with an interview
Measure: Acceptability of the treatment Time: from inclusion (day 0) to day 10This is a randomized, open-label phase II study designed to evaluate the safety and efficacy of etoposide in patients with the 2019 novel coronavirus (COVID-19) infection. Randomization will be performed with a 3:1 allocation ratio. Treatment will be comprised of etoposide administered intravenously at a dose of 150 mg/m2 on Days 1 and 4 in patients with COVID-19 infection meeting eligibility criteria. Subsequent doses of etoposide will be allowed if the investigator and treating physician believe the patient had clinical benefit from etoposide therapy but subsequently has evidence of recurrent clinical deterioration. Subjects randomized to control will receive standard of care treatment. No placebo will be used.
Description: An 8 point ordinal scale will be used to assess pulmonary status consisting of the following values: 8= Death; 7= Ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT), or need for vasopressors (dopamine ≥5 μg/kg/min OR epinephrine ≥0.1 μg/kg/min OR norepinephrine ≥0.1 μg/kg/min); 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= Discharged from hospital either to home with supplemental oxygen OR to inpatient rehabilitation/skilled nursing facility (+/- supplemental oxygen); 1= Discharged to home without supplemental oxygen
Measure: Change in pulmonary status Time: baseline, through study completion, an average of 45 daysDescription: number of events
Measure: Incidence of serious adverse events Time: baseline, through study completion, an average of 45 daysDescription: When calculating days of hospitalization, re-hospitalization or death occurring in the first 28 days should result in zero ascribed to time out of the hospital prior to readmission.
Measure: Length of hospitalization Time: From date of enrollment until the date of extubation, assessed study completion, an average of 45 daysDescription: Reintubations or death within 28 days will result in zero ascribed time off ventilator prior to reintubation
Measure: Ventilator free days Time: baseline, through study completion, an average of 45 daysIn the SAVE study patients with lower respiratory tract infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at high risk for progression to serious respiratory failure will be detected using the suPAR biomarker. They will begin early treatment with anakinra in the effort to prevent progression in serious respiratory failure. Also due to the potential co-existing immunodysfunction in the context of SARS-CoV-2 infection patients will also receive trimethoprim/sulfamethoxazole as part of chemoprophylaxis.
Description: The primary study endpoint is the ratio of patients who will not develop serious respiratory failure SRF until day 14. Patients dying before study visit of day 14 are considered non-achieving the primary endpoint.
Measure: The ratio of patients who will not develop serious respiratory failure (SRF) Time: Visit study day 14Description: Evaluation of clinical data (pO2/FiO2 and need of mechanical ventilation) between baseline and study visit day 14 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of the rate of patients who will not develop serious respiratory failure (SRF) until day 14 with historical comparators from Hellenic Sepsis Study Group Database Time: Visit study day 14Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 7
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 14
Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 7 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of SOFA score in enrolled subjects between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 14 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)
Measure: Change of Sequential organ failure assessment (SOFA) score in enrolled subjects between days 1 and 14 Time: Visit study day 1, visit study day 14Description: Change of cytokine stimulation from peripheral blood mononuclear cells of enrolled subjects will be compared between days 1 and 7
Measure: Change of cytokine production between days 1 and 7 Time: Visit study day 1, visit study day 7Description: Change of plasma inflammatory mediators measured levels will be compared between days 1 and 7
Measure: Change of plasma inflammatory mediators levels between days 1 and 7 Time: Visit study day 1, visit study day 7The global health emergency created by the rapid spread of the SARS-CoV-2 coronavirus has pushed healthcare services to face unprecedent challenges to properly manage COVID-19 severe and critical manifestations affecting a wide population in a short period of time. Clinicians are committed to do their best with a great uncertainty in this evolving crisis. Off label use of plenty of drugs has arisen the need for clinical trials to demonstrate their true role in the therapy. Based in unpublished experiences in China, Italy and Spain, intravenous IL-6 receptor inhibitors are now being tested in several trials but no data on subcutaneous formulations are available yet. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptors to inhibit IL-6 signalling, licensed in a subcutaneous route administration.
Description: Score ranges 1-7 Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized
Measure: Mean change in clinical status assessment using the 7-point ordinal scale at day 7 after randomisation Time: 7 days from enrolmentDescription: Days from the date of enrolment to the date of discharge
Measure: Duration of hospitalisation (days) Time: 30 days from enrolmentDescription: Number of deaths
Measure: Death Time: 30 days from enrolmentDescription: Time to become afebrile for a minimum period of 48 hours, without antipyretics
Measure: Time to become afebrile (days) Time: 30 days from enrolmentDescription: Days from enrolment to non-invasive mechanical ventilation
Measure: Time to non-invasive mechanical ventilation (days) Time: 30 days from enrolmentDescription: Days from enrolment to invasive mechanical ventilation
Measure: Time to invasive mechanical ventilation (days) Time: 30 days from enrolmentDescription: Days from enrolment to supplementary oxygen therapy withdrawal
Measure: Time to independence from supplementary oxygen therapy (days) Time: 30 days from enrolmentDescription: Scale ranges 1-7: Death Hospitalized, with mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Hospitalized, with non-invasive mechanical ventilation, a mask with a reservoir or oxygen with high flow nasal goggles. Hospitalized with oxygen supplement Hospitalized, without oxygen supplement, but in need of continued medical care (related or not with COVID) Hospitalized, without oxygen supplement and without the need for continued medical care Not hospitalized
Measure: Mean change in clinical status assessment using the 7-point ordinal scale at day 14 after randomisation Time: 14 days from enrolmentDescription: Number of adverse events and number of patients with adverse events
Measure: Incidence of serious and non-serious adverse events. Time: 30 days after enrolmentDescription: Number of adverse reactions that requires discontinuation of any drug in the study
Measure: Discontinuation due to adverse reactions Time: 30 days after enrolmentObservational cohort study aiming at comparing the incidence of ventilator-associated lower respiratory tract infections between COVID-19 patients and two control groups: one with influenza pneumonia and the other with no viral pneumonia.
Description: the incidence of ventilator associated pneumonia and ventilator associated tracheobronchitis
Measure: Cumulative incidence of ventilator-associated lower respiratory tract infection Time: from day 3 of mechanical ventilation to extubation or day 28 post-intubation.Description: incidence of ventilator-associated tracheobronchitis
Measure: Cumulative incidence of ventilator-associated tracheobronchitis Time: from day 3 of mechanical ventilation to extubation or day 28 post intubationDescription: incidence of ventilator-associated pneumonia
Measure: Cumulative incidence of ventilator-associated pneumonia Time: from Day 3 of mechanical ventilation to extubation or day 28 post intubation.Description: incidence of ICU-acquired bacteremia
Measure: the cumulative incidence of ICU acquired bacteremia diagnosed Time: from ICU admission to extubation or Day 28.Description: death in the ICU
Measure: ICU mortality Time: at day 28Description: death
Measure: Mortality Time: at day 28Description: number of days Under mechanical ventilation
Measure: the duration of mechanical ventilation Time: from the start of mechanical ventilation to extubation or day 28 post intubationDescription: number of days in the ICU
Measure: Length of stay in Intensive Care Unit Time: from admission to ICU until extubation or Day 28This study seeks to determine whether the virus which causes COVID-19, SARS-CoV-2, is shed in the stools of patients who are infected.
Description: Relative abundance of bacterial classes within taxonomic phyla and, more broadly, within their domain will be analyzed by sequencing the gut microbiome. These data will then be categorized among specific gastrointestinal disease types.
Measure: Correlation of Microbiome to Disease via Relative Abundance Found in Microbiome Sequencing Time: One yearDescription: To validate the methods used to sequence samples
Measure: Validation of Sequencing Methods Time: One yearIn this study, investigators will determine whether the early addition of HT-CCP to standard treatment improves the clinical outcome (as assessed by the Modified WHO Ordinal Scale) of patients with COVID-19 who are hospitalized but not yet in moderate or severe ARDS.
Description: The primary outcome will be the MOS numerical score (score 0-9) where a score of 0 attributes to 'no clinical evidence of infection' and a score of 9 attributes to 'death'. The eligibility requirements for this trial select individuals at level 3 or higher on the modified scale, but the day 14 outcome can be any one of 10 levels.
Measure: Modified WHO Ordinal Scale (MOS) score Time: Day 14Emergence of Covid-19 virus is associated with high frequency of extremely severe clinical pictures, with minor signs of CNS impairment (e.g. anosmia, headache). Since neurotropism is a common feature of coronavirus infection in animals, the investigators examine if indirect signs of CNS lesion are observed in association with severe Covid-19 infection.
Description: Change of neurofilament light chain (NFL) (pg/ml) level between first day of hospitalisation and one week; and change of GFAP (pg/ml) level between first day of hospitalisation and one week.
Measure: Change of neurodegeneration markers level Time: Level of neurofilament light chain (NFL) is dosed at inclusion (day 0) and week 1. Level of GFAP is dosed at inclusion (day 0) and week 1 (day 7).This phase III trial compares the effect of adding tocilizumab to standard of care versus standard of care alone in treating cytokine release syndrome (CRS) in patients with SARS-CoV-2 infection. CRS is a potentially serious disorder caused by the release of an excessive amount of substance that is made by cells of the immune system (cytokines) as a response to viral infection. Tocilizumab is used to decrease the body's immune response. Adding tocilizumab to standard of care may work better in treating CRS in patients with SARS-CoV-2 infection compared to standard of care alone.
Description: The 7-day length of invasive MV for each arm will be estimated with 95% confidence intervals (CIs) using the exact binomial distribution. Their difference by the arms will be tested by Cochran-Mantel-Haenszel (CMH) test stratified by the age group and Sequential Organ Failure Assessment (SOFA) score at significance level of 0.05.
Measure: 7-day length of invasive mechanical ventilation (MV) Time: Up to 7 daysDescription: Defined as death within 30-day after randomization. The 30-day mortality rate for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
Measure: 30-day mortality rate Time: Up to 30-day after randomizationDescription: The rate of ICU transfer for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
Measure: Rate of intensive care (ICU) transfer Time: Up to 2 yearsDescription: The rate of invasive mechanical ventilation for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
Measure: Rate of invasive mechanical ventilation Time: Up to 2 yearsDescription: The rate of tracheostomy for each arm will be estimated with 95% CIs using the exact binomial distribution. Their difference by the arms will be tested CMH test stratified by the age group and SOFA score at significance level of 0.05.
Measure: Rate of tracheostomy Time: Up to 2 yearsDescription: Will first be described by median and inter-quartile, and then compared between two arms by Wilcoxon Sum-Rank test
Measure: Length of ICU stay Time: Up to 2 yearsSpectrum of skin lesions may arise during Covid-19 virus infection. It includes non-specific urticaria, aphtoids lesions, but also acrosyndromes, in particular suggestive of chilblains. Pathological findings showed thrombocytic lymphocytic vasculitis. Chilblains are sometimes associated with Raynaud's phenomenon or acrocyanosis. Dermatological features may present pathophysiological similarities with the inflammatory and respiratory vascular disturbances, which makes all the gravity of this disease, or even with other organs. Indeed, genetic conditions such as familial lupus chilblains, linked to a mutation of TREX1 gene, and SAVI (Sting associated vasculopathy with onset on infancy) have similar clinical presentations. In particular, SAVI associates both acral skin and lung damage, and auto-antibodies. They have recently been identified as type I interferonopathies. Hallmark is interferon signature, i.e. hyperexpression of type I interferon in the blood. The investigators hypothesize Covid-19 may lead to similar skin involvement as in type I interferonopathies. The interferon pathway is involved in anti-viral defense. Covid-19 could cause excessive activation of this pathway. In addition, hyperactivation of the type I interferon pathway leads to modulation of the adaptive immune response. Production of autoantibodies, in particular antiphospholipid antibodies, have thrombogenic properties. Searching for acquired hemostasis disorders and high level of interferon secondary Covid-19 virus infection, could explain this new and misunderstood skin disorder. Then, targeted therapies, both treating and preventing, could be considered.
Description: Searching for presence or absence of abnormal acquired thrombophilic condition as antibodies, hemostasis disturbances. Presence or absence of thrombophilic markers in the blood
Measure: Biological acquired thrombophilia Time: 1 dayDescription: Dosing transcriptomic interferon signature in a blood sample. Presence or absence of interferon in the blood
Measure: Overexpression of interferon type I Time: 1 dayThis is a multicenter; double blind randomized controlled study investigating the role of remote intercessory multi-denominational prayer on clinical outcomes in COVID-19 + patients in the intensive care unit. All patients enrolled will be randomized to use of prayer vs. no prayer in a 1:1 ratio. Each patient randomized to the prayer arm will receive a "universal" prayer offered by 5 religious denominations (Christianity, Hinduism, Islam, Judaism and Buddhism) in addition to standard of care. Whereas the patients randomized to the control arm will receive standard of care outlined by their medical teams. During ICU stay, patients will have serial assessment of multi-organ function and APACHE-II/SOFA scores serial evaluation performed on a daily basis until discharge. Data assessed include those listed below.
Description: This study will measure the difference in mortality of COVID-19 patients who are admitted to ICU - given prayer vs no prayer as an adjunct to standard therapy.
Measure: Impact of multi-denominational prayer on clinical outcomes of critically ill COVID-19 patients in the Intensive Care Unit on mortality. Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysDescription: APACHE II uses 0-71 scale, the higher the score the higher the risk for mortality.
Measure: Difference in patient outcomes - Acute Physiology and Chronic Health Enquiry. APACHE II score. Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 days.Description: The higher the SOFA score the increased likelihood of organ failure.
Measure: Difference in patient outcomes - Sequential Organ Failure Assessment - SOFA Score Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysDescription: A prolonged length of time in ICU increases mortality.
Measure: Difference in patient outcomes - Length of stay in ICU. Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysDescription: A prolonged length of time with ventilator support increases mortality.
Measure: Difference in patient outcomes - Length of ventilator support Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysDescription: A prolonged length of time with vasopressor support increases recovery time.
Measure: Difference in patient outcomes - length of vasopressor support Time: daily until patient recovers and moves out of ICU or exits the study, up to 30 daysUntil the first half of April, Colombia has more than 2,800 infected cases and a hundred deaths as a result of COVID-19, with Antioquia being the third department with the highest number of cases. Official records indicate that, in Colombia, the first case was diagnosed on March 6, 2020, corresponding to a patient from Italy. However, in conversations with several infectologists and intensivists from Medellín, it was agreed that clinical cases similar to the clinical presentation that is now recognized as COVID-19 had arisen since the end of 2019 when it was still unknown to everyone. The previous suggests that the virus was already circulating in the country since before March 6, 2020. But at that moment, there were no tools to make a clinical identification, nor to diagnose it from the laboratory's point of view. Considering as real the hypothesis that the infection has been circulating in the country since before the first official diagnosis, the question arises: Why does not the country still has the same healthcare and humanitarian chaos that countries such as Italy and Spain are suffering at this time? To answer this question may be that there are differences in vaccination rates with BCG (Bacille Calmette-Guérin or tuberculosis vaccine), which is significantly higher in Latin America compared to those in Europe. This finding could explain to some extent the situation in the country, since previous studies have shown the influence that this vaccine can have on the immune response against various other pathogens, including viruses. Among the population at risk of infection, health-care workers due to their permanent contact with patients are the population group with the highest risk of contracting SARS-Cov-2 and developing COVID-19 in any of its clinical manifestations, and currently there are no vaccines or proven preventive interventions available to protect them. For this reason, this research study aims to demonstrate whether the centennial vaccine against tuberculosis (BCG), a bacterial disease, can activate the human immune system in a broad way, allowing it to better combat the coronavirus that causes COVID-19 and, perhaps, prevents the complications that lead the patient to the intensive care unit and death. In the future, and if these results are as expected, they may be the basis for undertaking a population vaccination campaign that improves clinical outcomes in the general population.
Description: Incidence of COVID-19 cases confirmed or probable in the study population
Measure: Primary outcome Time: From date of randomization to 360 day of the studyDescription: Incidence of severe or critical infection in COVID-19 cases
Measure: Secondary outcome Time: From date to diagnosis to 1 month afterDescription: Lethality of the infection in both groups
Measure: Secondary outcome Time: From date to diagnosis to 1 month afterDescription: Assess the safety (frequency, seriousness, and severity of adverse events) of BCG vaccination
Measure: Secondary outcome Time: From date of randomization to 7 day of the studyDescription: Prevalence of SARS-Cov-2 infection
Measure: Secondary outcome Time: At baseline evaluationThe aim of the study is to determine the incidence o of SARS-cov2 infection among health care workers highly exposed to covid 19 during 10 weeks et to analyze the determinants of their occupational and environmental exposure. Every 14 days, we performed SARS-Cov2 RT- PCR, serological testing and clinical questionnaire among a cohort of 100 HCW with a high degree of exposure to covid19 infection. Information about occupational exposure as the workplace, the activity of care, the characteristics of patient infected are captured, as well as environmental or personal exposure. The results will support the design of a new care organization and will define new ways of protection for patients (covid or not covid 19) and prevention for HCW.
This is a multi-center prospective study that aims to investigate the clinical and immunologic impact of SARS-CoV-2 infection in pregnant women and neonates. The goal is to recruit 200 SARS-CoV-2 infected pregnant women starting at 24 weeks of gestation in a neonatal network of 45.000 birth a year. Clinical data will be collected from women and neonates. Upper airways samples will be obtained from both for bio-markers investigation. Finally, maternal and umbilical cord serum and human milk will be obtained for antibody assessment.
Description: Presence of IgM in Umbilical Cord or presence of virus in human milk with infected neonate
Measure: Vertical transmission Time: 96 hours from birthDescription: Presence of IgG in umbilical cord
Measure: Neonatal protection due to maternal antibodies Time: 24 weeks of gestation to birthDescription: Respiratory distress, hypothermia, poor feeding and others
Measure: Increase risk of neonatal morbidity Time: up to 30 days of lifeACCESS enables individuals to contribute to critical research, via an iOS and Android smartphone mobile application. ACCESS combines patient reported outcomes, data from wearable devices and real-world data (such as claims, EHRs, etc), with an opt-in to participate in current and future studies for diagnostics, treatments and vaccines. The data that people share can be quickly and anonymously matched to research studies, providing researchers with a foundational framework for dynamic research at scale and participants a way to be personally matched and prescreened for future research.
Description: To use multifaceted participant data consisting of participant reported outcomes, environmental surface and presence or absence of COVID-19 based on testing results, prescription medications (including off-label use), claims, lab, and medical record data to develop population-based models of disease risk, short and long-term outcomes, and efficacy of interventions and prevention measures.
Measure: Development of population-based models of disease risk Time: Up to 10 yearsDescription: To leverage geolocation and lab results to provide population-level real-time data regarding disease burden at the community, state and national levels.
Measure: Relation between disease burden and geolocation Time: Up to 10 yearsDescription: To specifically identify medications and regimens that address disease symptoms
Measure: Effect of medications on symptoms of COVID19 Time: Up to 10 yearsDescription: To specifically identify medications and regimens that treat and reduce disease severity.
Measure: Effect of medications on disease severity of COVID19 Time: Up to 10 yearsDescription: To identify regional variations in disease incidence and outcomes.
Measure: Rate of COVID19 infection and disease outcomes Time: Up to 10 yearsDescription: To understand long-term outcomes such as risk of pulmonary and cardiovascular disease complications.
Measure: Effect of COVID19 on health outcomes Time: Up to 10 yearsDescription: To conduct long-term follow up of individuals who tested positive for COVID-19 compared to demographically matched individuals that did not.
Measure: Long-term follow up and recontact Time: Up to 10 yearsNational multicentre epidemiological study to describe retrospectively and prospectively the clinical outcomes of patients with a suspected coronavirus infection (either confirmed or not) while receiving a medical treatment for the underlying cancer
Description: Mortality rate, defined as the proportion of patients who are dead 28 days after the date of the diagnostic procedure for the 2 cohorts of patients (positive and negative).
Measure: Mortality of cancer patients under active anticancer treatment Time: 28 days after the date of the diagnostic procedureDescription: Overall survival will be defined as the time from the date of the first diagnostic procedure (either diagnostic test or chest imaging) to the date of death due to any cause.
Measure: Overall survival Time: 6 months (i.e. at the the time of last patient last visit)Description: The duration of hospitalization (from the date of hospitalization to the date of definitive discharge for live patients)
Measure: Hospitalizations Time: 28 days after the date of the diagnostic procedureDescription: Cause of death, related or not to the COVID-19
Measure: Death Time: 6 months (i.e. at the the time of last patient last visit)Description: Associated complications described by their type
Measure: Complications Time: 28 days after the date of the diagnostic procedureDescription: proportion of hospitalizations
Measure: Hospitalizations Time: 28 days after the date of the diagnostic procedureDescription: To describe accurately patients' characteristics in terms of demographics
Measure: Patients' characteristics Time: At the date of the diagnostic procedureDescription: To describe accurately patients' characteristics in type of tumor
Measure: Patients' characteristics Time: At the date of the diagnostic procedureDescription: To describe accurately patients' characteristics in type of anticancer treatment,
Measure: Patients' characteristics Time: At the date of the diagnostic procedureDescription: To describe accurately patients' characteristics in terms of comorbidities
Measure: Patients' characteristics Time: At the date of the diagnostic procedureBackground Rapid European COVID-19 Emergency Research response (RECoVER), is a project involving 10 international partners that has been selected for funding by the European Union under the Horizon 2020 research framework responding to call topic SC1-PHE-CORONAVIRUS-2020: Advancing knowledge for the clinical and public health response to the SARS-CoV-2 epidemic. MERMAIDS 2.0 is the hospital care study within RECOVER. Rationale Detailed patient-oriented studies are needed to determine the spectrum of SARS-CoV-2 disease and the combined influences of age, comorbidities and pathogen co-infections on the development of severe disease, together with virological and immunological profiles. This research is key to understanding the pathophysiology and epidemiology of this new disease, as well as to identifying potential targets for therapeutic or preventive interventions. Objective To establish the prevalence, disease spectrum and severity, clinical features, risk factors, spread and outcomes of novel 2019 coronavirus infection (SARS-CoV-2) in Hospital Care. Study design Prospective observational cohort study in selected European countries. Study population Children and adults with 1) acute respiratory illness (ARI) presenting to hospital care during the SARS-CoV-2 epidemic (including both COVID-19 and non-COVID-19 patients) and 2) patients with confirmed COVID-19 infection, but with atypical presentation (non-ARI) or with nosocomial acquisition. Sites can optionally participate in the following tiers: Tier 0 (Clinical data collection only) - Clinical data will be collected but no biological samples will be obtained for research purposes. Summary of the illness episode and outcome, including a selection of risk factors and comorbidities and medications. Tier 1 (Clinical data and biological sampling) - Clinical samples and data will be collected on enrolment day and then at scheduled time points. Tier 2 (Clinical data an extended biological sampling). Optional add-on study In a subset of sites and patients, COVID-19 positive patients will be followed post-discharge for 6 months to study clinical recovery and long-term sequelae Main study parameters/endpoints: Prevalence of COVID-19 among patients with acute respiratory illness. COVID-19 disease spectrum and host and pathogen risk factors for severity. Long-term sequelae of COVID-19 requiring hospital care. Proportion hospital-acquired COVID-19 infections and characteristics of nosocomial transmission. Study Duration Scheduled 2 years and based on COVID-19 dynamics. Nature and extent of the burden associated with participation, benefit and group relatedness This study is observational in nature. There will be no direct benefit to research participants. The study may include biological sampling in addition to sampling required for medical management. The results of the tests done on these samples may not contribute to improving the participant's health. Minimal inconvenience and discomfort to the participant may arise from study visits and biological sampling.
Suspension of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors and Adverse Outcomes in Hospitalized Patients With Coronavirus Infection.
Description: The primary outcome of the study will be days alive and outside the hospital (DAOH) at 30 days. This endpoint will be calculated for each included patient and the calculation will be from the date of randomization to the 30-day post-randomization. The DAOH endpoint represents the follow-up time (30 days) subtracted from the hospitalization days and/or the days between death and the end of follow-up.
Measure: Median days alive and out of the hospital Time: 30 daysDescription: Cardiovascular outcomes such as evolution with acute myocardial infarction, stroke, myocarditis, pericarditis, arrhythmias requiring treatment, thromboembolic phenomena, increase in troponin and D-dimer, respiratory failure, hemodynamic decompensation, sepsis, renal failure and death.All events will be reported according to CTCAE 4.0
Measure: Number of participants with adverse cardiovascular outcomes and new worsening heart failure Time: 30 daysDescription: Evaluation of test results troponin, NT-ProBNP, BNP, and D-dimer will also be assessed as secondary outcome.
Measure: Cardiovascular biomarkers related to COVID-19 Time: up to 30 daysThis study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in hospitalized patients with moderate COVID-19 disease.
Description: Number and severity of adverse events
Measure: Phase 1: Frequency and Severity of Adverse Events (AE) Time: Up to 12 monthsDescription: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR
Measure: Time to Clearance of SARS-CoV-2 Time: Up to 12 monthsDescription: Time from the date of randomization to the first date of clinical improvement of cough.
Measure: Time to Clinical Improvement of cough Time: Up to 28 daysDescription: Time from the date of randomization to the first date of clinical improvement of radiological evaluation of disease related chest x-ray
Measure: Time to Clinical Improvement in radiological evaluation of disease related chest x-ray Time: Up to 28 daysDescription: Proportion of subjects who achieve pulmonary clearance
Measure: Rate of Pulmonary Clearance Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of radiological evaluation of disease related chest x-ray
Measure: Rate of Clinical Improvement of radiological evaluation of disease related chest x-ray Time: Up to 28 daysDescription: Number and severity of adverse events
Measure: Phase 2: Frequency and Severity of Adverse Events (AE) Time: up to 12 monthsDescription: Time to medical discharge as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by time to medical discharge Time: up to 12 monthsDescription: Hospital utilization will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by hospital utilization Time: up to 12 monthsDescription: Mortality rate will be measured as an assessment of overall clinical benefit
Measure: Overall Clinical Benefit by measuring mortality rate Time: up to 12 monthsDescription: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.
Measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score Time: Up to 28 daysDescription: Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).
Measure: Time to Pulmonary Clearance Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of cough
Measure: Rate of Clinical Improvement of cough Time: Up to 28 daysDescription: Proportion of subjects who achieved clinical improvement of fever
Measure: Rate of Clinical Improvement of fever Time: Up to 28 daysDescription: Time from the date of randomization to the first date of clinical improvement of fever
Measure: Time to Clinical Improvement of fever Time: Up to 28 daysDescription: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR
Measure: Rate of Clearance of SARS-CoV-2 Time: Up to 12 monthsThis study is a retrospective cohort trial to assess the efficacy of remdesivir in hospitalized adult patients diagnosed with COVID-19. The study is a multicenter trial which will be carried out on different sites in France. This trial is retrospective and will analyze the data collected during treatment.
Description: Study the prognostic factors of the clinical course of patients on Day 15 under treatment with remdesivir. Clinical progress will be categorized using a 7-point ordinal scale.
Measure: Clinical course on Day 15. Time: 15 daysDescription: Explore the prognostic factors of the clinical course of patients on Day 3
Measure: Clinical course on Day 3. Time: 3 daysDescription: Explore the prognostic factors of the clinical course of patients on Day 8
Measure: Clinical course on Day 8 Time: 8 daysDescription: Explore the prognostic factors of the clinical course of patients on Day11
Measure: Clinical course on Day 11. Time: 11 daysDescription: Explore the prognostic factors of the clinical course of patients on D29.
Measure: Clinical course on Day 29. Time: 29 daysDescription: Duration of treatment with remdesivir
Measure: Duration of treatment Time: 29 daysDescription: PaO2 / FiO2 and artificial ventilation; platelets; bilirubin; average blood pressure and use of vasoactive drugs; Glasgow score; creatinine.
Measure: Sepsis-related Organ Failure Assessment score Time: Day 3, 8, 11, 15 and 29Description: Duration without mechanical ventilation within 29 days of initiation of treatment with remdesivir
Measure: Duration without mechanical ventilation Time: 29 daysDescription: Mortality at 29 days after initiation of treatment with remdesivir.
Measure: Mortality Time: 29 daysDescription: Evaluate the safety of the treatment with cumulative incidence of grade 3 and 4 adverse events (AEs).
Measure: cumulative incidence of grade 3 and 4 adverse events (AEs). Time: 29 daysDescribe the main clinical features impacting the food intake, and therefore the nutritional status of a population infected by a coronavirus.
Description: Self assessment on the SEFI (Self-Evaluation of Food Intake) scale at one month after hospital discharge: 0 corresponds to the worsen score (no ingesta) and 10 corresponds to the best (same ingesta than before the disease)
Measure: Evaluation of food intake at 1 month after discharge from hospital for COVID Time: one month after hospital dischargeDescription: Self-reported weight in kilograms, or in the absence of self-reported variations before the disease, during hospitalisation, at hospital discharge, one month after hospital discharge
Measure: Weight variation during the infection Time: one month after hospital dischargeDescription: Effect of these factors (anorexia, dysgeusia, Ear Nose and Throat pain, swallowing disorders, intestinal transit disorders...) on SEFI and weight
Measure: Clinical signs limiting food intake Time: one month after hospital dischargeDescription: Effect of these factors (supply difficulties, disease-related food disgust, limiting food habits or prior diet, hydration difficulties, need for help) on SEFI and weight
Measure: Factors limiting food intake Time: one month after hospital dischargeDescription: Effect of nutritional strategy and interventions that were implemented (nutritional advice, adapted meals, oral nutritional supplementation, enteral and parenteral nutrition during hospitalisation and one month after hospital discharge) on SEFI and weight
Measure: Implemented nutritional strategy Time: one month after hospital dischargeDescription: Effect of pre-existing chronic disorders (pulmonary, chronic inflammatory bowel disease, cardio-vascular disease, diabetes, obesity, cognitive disorders, immunodepression, cancer, inflammatory joint disorder) on SEFI and weight
Measure: Pre-existing chronic disorders Time: one month after hospital dischargeDescription: Quantifying unscheduled consultations or hospitalisations in the month following discharge from hospital
Measure: Covid-19 repercussions Time: one month after hospital dischargeThis original study will assess the impact of the coronavirus health crisis on the management of patients undergoing medical treatment for cancer, in particularly on the modification of the hospital organization. It will also provide a record of the progress of patients who will have been treated during the epidemic period and infected by the virus. We will also assess the psychological impact of the pandemic in patients but also in caregivers
Description: Proportion of patients with modification of the treatments administered
Measure: To assess the impact of the COVID-19 pandemic on the modifications of treatments administered in hospital (day units) to patients with cancer or malignant hemopathy Time: up to 6 monthsDescription: Proportion of patients with change in the rate of treatment administration
Measure: To assess the impact of the COVID-19 pandemic on the change in the rate of treatment administration in hospital (day units) to patients with cancer or malignant hemopathy Time: up to 6 monthsDescription: Proportion of patients with change in the number of cures administered
Measure: To assess the impact of the COVID-19 pandemic on the number of cures administeredin hospital (day units) to patients with cancer or malignant hemopathy Time: up to 6 monthsDescription: Proportion of patients with change of modality of administration (home administration to replace day hospital administration, teleconsultation uses)
Measure: To assess the impact of the COVID-19 pandemic on change of modality of administration in hospital (day units) to patients with cancer or malignant hemopathy Time: up to 6 monthsDescription: Score of questionnaires of Perceived Stress Scale [0-40 points]
Measure: Evaluate the perceived stress on cancer patients treated in unit day of hospital Time: up to 6 monthsDescription: Score of questionnaires of Impact of Event Scale-Revised [0-88 points]
Measure: Evaluate the post-traumatic stress on cancer patients treated in unit day of hospital Time: up to 6 monthsDescription: Score of questionnaires of sleep disorders (ISI scale, 0-28 points)
Measure: Evaluate the sleep disorders on cancer patients treated in unit day of hospital Time: up to 6 monthsDescription: Score of questionnaires of quality of life (FACT-G scale)
Measure: Evaluate the quality of life on cancer patients treated in unit day of hospital Time: up to 6 monthsDescription: Score of questionnaires of cognitive complaints (Fact-Cog scales; 0-148 points)
Measure: Evaluate the cognitive complaints on cancer patients treated in unit day of hospital Time: up to 6 monthsDescription: Score of questionnaires of Perceived Stress Scale [0-40 points]
Measure: Evaluate the perceived stress on caregivers (perceived stress, post-traumatic stress, burnout, feeling of personal effectiveness) Time: up to 3 monthsDescription: Score of questionnaires of Impact of Event Scale-Revised [0-88 points]
Measure: Evaluate the post-traumatic stress on caregivers (perceived stress, post-traumatic stress, burnout, feeling of personal effectiveness) Time: up to 3 monthsDescription: Score of questionnaires of burnout ((Maslach Burn Out Inventory scale, 0-132 points)
Measure: Evaluate the burnout on caregivers (perceived stress, post-traumatic stress, burnout, feeling of personal effectiveness) Time: up to 3 monthsDescription: Score of questionnaires of feeling of personal effectiveness (0-30 points)
Measure: Evaluate the feeling of personal effectiveness on caregivers (perceived stress, post-traumatic stress, burnout, feeling of personal effectiveness) Time: up to 3 monthsPhase I / II multicentre, randomized and controlled clinical trial to evaluate the efficacy of treatment with hyperimmune plasma obtained from convalescent antibodies of COVID-19 infection.
Description: Incidence of Adverse Events and Serious Adverse Events grade 3 and 4, related to the product under investigation or the administration procedure, graduated according to the common toxicity criteria scale (CTCAE).
Measure: Safety: Incidence of Adverse Events and Serious Adverse Events grade 3 and 4, related to the product under investigation or the administration procedure, graduated according to the common toxicity criteria scale (CTCAE). Time: 30 days after enrollmentDescription: IL-6> 40 pg / mL, D-dimer> 1500, ferritin> 1000ng / mL.
Measure: Efficacy: Any of the following analytical data after 72h of randomization. Time: Day +21 after randomizationDescription: IL-6> 40 pg / mL, D-dimer> 1500, ferritin> 1000ng / mL until the cure test.
Measure: Efficacy: Proportion of patients who develop analytical alterations. Time: Day +21 after randomization.Prospective registry for multimodal assessment of neuromuscular pathology associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, enrolling consecutive patients with corona virus disease 2019 (Covid-19), who are admitted to the intensive care unit of the department of anesthesiology and intensive care medicine, or the department of neurology at Tübingen University Hospital.
Description: Elevation of creatine kinase during hyperacute phase of corona virus disease 2019 (Covid-19)
Measure: Rate of elevated creatine kinase in hyperacute phase Time: 1 weekDescription: Elevation of creatine kinase during hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Rate of elevated creatine kinase Time: 24 monthsDescription: Two-peak elevation of creatine kinase during acute phase of corona virus disease 2019 (Covid-19)
Measure: Rate of two-peak elevation of creatine kinase during acute phase Time: 30 daysDescription: Presence of myositis-specific antibodies on admission, at two weeks, and at end of follow-up
Measure: Rate of myositis-specific antibodies Time: 24 monthsDescription: Presence of antimyocardial antibodies on admission, at two weeks, and at end of follow-up
Measure: Rate of antimyocardial antibodies Time: 24 monthsDescription: Level of creatine kinase elevation in the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19) assessed by the area under the curve (AUC)
Measure: Area under the curve (AUC) of elevated creatine kinase Time: 24 monthsDescription: Maximal value of creatine kinase elevation in the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Peak-levels of elevated creatine kinase Time: 24 monthsDescription: Maximal value of troponin in the acute phase of corona virus disease 2019 (Covid-19)
Measure: Peak-levels of troponin Time: 30 daysDescription: Maximal value of urine myoglobin in the acute of corona virus disease 2019 (Covid-19)
Measure: Peak-levels of urine myoglobin Time: 30 daysDescription: Muscle hyperechogenicity in the upper and lower extremities, the accessory respiratory serratus anterior muscle, and abdominal wall according to qualitative ultrasound assessment (Heckmatt score) during the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Rate of muscle hyperechogenicity Time: 24 monthsDescription: Peak-muscle hyperechogenicity in the upper and lower extremities, the accessory respiratory serratus anterior muscle, and abdominal wall according to qualitative ultrasound assessment (Heckmatt score) during the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)
Measure: Peak-muscle hyperechogenicity Time: 24 monthsThe aims of this study is to define the genetic bases of COVID-19 related disease heterogeneity in frail population, to carry out a retrospective study on individuals w/wo symptoms to verify the reliability of a prognostic/diagnostic test based on IgM/IgG analysis and on the presence of genetic profiling and to explore the therapeutic potential of the modulation of ACE2 expression.
Description: BioMedomics Rapid IgM-IgG Combined Antibody Test for COVID-19 is immunochromatography based. The test card contains colloidal gold-labeled recombinant novel coronavirus antigen and quality control antibody colloidal gold marker, two detection lines (G and M lines) and one quality control line (C) fixed on a nitrocellulose membrane. When 10 microL of test sample is added to the sample well of the test cassette, the sample will move forward along the test card via capillary action. If the sample contains IgM antibody, the antibody will bind to the colloidal gold-labeled novel coronavirus antigen. The antibody/antigen complex will be captured by the anti-human IgM antibody immobilized on the membrane, forming a red M line and indicating a positive result for the IgM antibody. If the sample contains IgG antibodies, the same thing happens, forming a red G line and indicating a positive result for the IgG antibody. If neither antibody is present, a negative result is displayed.
Measure: Retrospective study on individuals with or without symptoms to verify the reliability of a prognostic/diagnostic test based on IgM/IgG analysis. Time: 6 monthsDescription: By an in silico analysis, we found 2 missense variants in ACE2 gene annotated at residues 82 (rs766996587) and 355 (rs961360700) involved in PPIs with MAF<0.01. Variants in other residues of the ACE2 may affect protein structure and/or activity/localization, influence the binding of the spike protein and thus the virus ability to enter the respiratory tract.In light of its relevance in cell entry, pharmacological approaches aimed at modulating ACE2 expression, through the modulation of SIRT1 activity in the lung or by selective oligo antisense treatment, should help in counteracting COVID-19 infection. Annotated SNPs evaluation of the TMPRSS2 gene showed 4 exonic common polymorphisms (MAF>1%); of these, rs12329760 is a missense variant in the SRCR domain mediating PPI and ligand binding. Common SNPs are at the 3'UTR, possibly involved in regulating mRNA stability and several rare variants mapped in exons encoding the peptidase domain, potentially affecting protein activity.
Measure: ACE2 expression in patients with COVID-19 infection Time: 6 monthsPurpose: To determine the number of asymptomatic individuals who have antibodies to SARS-CoV-2, the virus which causes COVID-19
Description: Presence or absence of IgG antibodies to SARS-CoV2
Measure: Percentage of Asymptomatic patients with an IgG response from SARS-CoV-2 infection. Time: at enrollmentDescription: swab for presence of SARS-CoV-2 virus
Measure: Percentage of Asymptomatic patients with viral presence of SARS-CoV-2 infection. Time: at enrollmentA prospective, longitudinal, observational cohort study looking at patients following COVID-19 disease using multi-parametric magnetic resonance imaging (MRI) to assess the degree and prevalence of organ injury.
Description: In patients recovering from COVID-19 disease: Characterise using summary statistics the prevalence and severity of organ volume change and damage to heart, kidneys and liver
Measure: Characterise prevalence and severity of organ volume change and damage (heart, kidneys and liver) Time: 12 MonthsDescription: In patients recovering from COVID-19 disease: To characterise using summary statistics the prevalence and severity of organ volume change and damage in lung, pancreas and spleen
Measure: Characterise prevalence and severity of organ volume change and damage (lung, pancreas and spleen) Time: 12 MonthsDescription: In patients recovering from COVID-19 disease: Characterise liver damage as assessed by liver volume in liters, iron corrected T1 (cT1) in milliseconds, liver fat content as %, liver T2star in milliseconds (a correlate of liver iron content)
Measure: Change from Baseline in liver-specific biomarkers: volume, iron corrected T1(cT1), fat content and T2star Time: 6 MonthsDescription: In patients recovering from COVID-19 disease: Characterise heart and spleen damage as assessed by liver volume in liters as well as kidney, liver and pancreas damage as assessed by volume in liters, iron corrected T1 (cT1) in milliseconds, fat infiltration as %, T2star in milliseconds (a correlate of liver iron content).
Measure: Change from Baseline in organ-specific biomarkers characterising organ volume change in the heart and spleen along with organ volume and damage in the kidney, liver and pancreas assessed by volume, iron corrected T1 (cT1) and fat infiltration Time: 12 MonthsDescription: In patients recovering from COVID-19 disease: Change in patient reported outcome measures collected to assess breathlessness and its effect on overall health and daily life assessed by Dyspnea-12. Each question is assigned a value between: none, mild, moderate and severe and is used to assess breathing characteristics.
Measure: Change in patient reported outcome measured by the Dyspnea-12 questionnaire Time: 12 MonthsDescription: In patients recovering from COVID-19 disease: Change in patient reported outcome measures collected to assess breathlessness and its effect on overall health and daily life assessed by the St. George's Respiratory questionnaire. Each section comprises of questions in various formats allowing to assess which aspects of the illness cause the participant the most problems in daily life.
Measure: Change in patient reported outcome measured by the St. George's Respiratory questionnaire (SGRQ) Time: 12 MonthsDescription: In patients recovering from COVID-19 disease: Change in patient reported outcome measures collected to assess breathlessness and its effect on overall health and daily life assessed by the EQ-5D-5L questionnaire. Two main sections provide the opportunity to capture statements best describing a participant's daily health and a scale form 0 to 100 capturing self-reported health stats. (100 being the best health imaginable and vice versa)
Measure: Change in patient reported outcome measured by the EQ-5D-5L questionnaire Time: 12 MonthsDescription: In patients recovering from COVID-19 disease: Difference from Baseline in degree of change in liver MR-derived biomarkers with and without known genetic variants associated with liver disease (e.g., PNPLA3) using a paired t-test (or non-parametric alternative)
Measure: Degree of change in liver MR-derived biomarkers Time: 12 MonthsTo compare various treatments provided to positive COVID-19 patients at locations across the OSF Ministry. Provide the opportunity to compare the effectiveness of various treatments and treatment timelines provided to specific cohorts of patients that have the potential to impact future treatment plans for COVID-19 patients and/or future research hypotheses.
Healthcare personnel are at an increased risk of exposure to SARS-CoV-2 infection while handling such patients. Currently, there is no treatment available for SARS-CoV-2 and stringent preventive measures are advised to avoid or minimize risk of exposure to healthcare workers. There are in vitro studies available which show inhibition of corona virus by hydroxychloroquine, a widely-used agent against malaria and certain autoimmune conditions and of low-cost and limited toxicity. However, evidence regarding its effects in patients is limited. We plan to conduct a randomized controlled trial to evaluate the safety and potential prophylactic efficacy of hydroxychloroquine in preventing secondary SARS-CoV-2 infection among healthcare workers at high-risk of exposure while managing such patients.
Description: Negative RT-PCR for SARS-CoV-2 both at baseline and at end of 12 weeks in experimental arm
Measure: Prevention of SARS-CoV-2 as determined by negative RT-PCR at the end of 12 week study period Time: From date of randomization until study completion 12 weeks after treatment initiationDescription: To assess the presence or absence of side effects from HCQ treatment.
Measure: Safety as determined by presence or absence of any adverse event related with hydroxychloroquine treatment Time: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiationDescription: Symptomatic infection by SARS-CoV-2 defined as cough, dyspnea, fever, myalgia, arthralgia or rhinorrhea.
Measure: Confirmed SARS-CoV-2 infection based on symptoms and confirmed by RT-PCR Time: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiationDescription: Disease severity including i) asymptomatic. ii) Mild symptoms but ambulatory. iii) Moderate symptoms requiring hospitalisation. iv) severe symptoms requiring ICU care and oxygen. v) Severe symptoms requiring assisted mechanical ventilation. vi) Death.
Measure: Clinical disease severity in confirmed SARS-CoV-2 participants Time: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiationDescription: Symptomatic non-COVID viral infection (any other acute respiratory illness with fever but without evidence of epidemiological risk factors such as close contact with SARS-CoV-2 positive patient or travel to or residence in high-risk area).
Measure: Incidence of any acute respiratory infection Time: From date of randomization until the appearance of symptoms or study completion 12 weeks after treatment initiationThe main objectives of this study are 1) to establish the prevalence of SARS-CoV-2 in asymptomatic healthcare workers (HCWs) in an early phase of community spread as well as 2) to monitor the future spread of the disease by assessing serological responses to SARS-CoV-2 in symptomatic and asymptomatic HCWs over time and 3) to improve the assessment of the immune response and its protective effect as well as the assessment of infectivity of affected HCWs and 4) to evaluate the value and significance of antibody formation and serological antibody tests and 5) to be able to evaluate possible future preventive and / or therapeutic approaches against SARS-CoV-2
Description: Anti-SARS-COV2 S protein IgG ELISA
Measure: Number of people with detectable antibodies to SARS-COV2 Time: 1 yearDescription: SARS-COV2 PCR
Measure: Number of people with detectable SARS-COV2 nucleic acid Time: 1 yearDescription: Anti-SARS-COV2 S protein IgG ELISA
Measure: Number of people with detectable antibodies to SARS-COV2 Time: 2 yearsDescription: Anti-SARS-COV2 S protein IgG ELISA
Measure: Number of people with detectable antibodies to SARS-COV2 Time: 3 yearsDescription: Anti-SARS-COV2 S protein IgG ELISA
Measure: Number of people with detectable antibodies to SARS-COV2 Time: 4 yearsDescription: Anti-SARS-COV2 S protein IgG ELISA
Measure: Number of people with detectable antibodies to SARS-COV2 Time: 5 yearsDescription: SARS-COV2 PCR
Measure: Number of people with detectable SARS-COV2 nucleic acid Time: 2 yearsDescription: SARS-COV2 PCR
Measure: Number of people with detectable SARS-COV2 nucleic acid Time: 3 yearsDescription: SARS-COV2 PCR
Measure: Number of people with detectable SARS-COV2 nucleic acid Time: 4 yearsDescription: SARS-COV2 PCR
Measure: Number of people with detectable SARS-COV2 nucleic acid Time: 5 yearsPatient are being asked to provide respiratory and blood samples for a clinical research study because the patients have a virus called the novel coronavirus, or SARS-CoV-2, that causes the disease known as Covid-19. Investigators do not know a lot about this virus, including all the ways it travels from person to person. Investigators also do not know if a person will get sick or not from the virus after being in close contact with someone who has the virus. Because of this, investigators are performing research on the virus found in respiratory secretions to get more information on how investigators can best detect and treat this new virus in the future. Primary Objective - To determine the clinical characteristics and outcomes of Covid-19 in children. - To characterize the clinical risk factors of Covid-19 in children.. Secondary Objectives - To characterize the immunological risk factors and serologic response to SARS-CoV-2 infection in children.- To evaluate the duration of viral shedding in children. - To evaluate the duration of SARS-CoV-2 viral shedding in children. Exploratory Objective
Description: Clinical characteristics, including demographics, underlying diagnosis, and signs/symptoms, and outcomes, such as hospitalization, oxygen requirements, and mortality, will be summarized with counts and percentages.
Measure: Characteristics and outcomes of acute respiratory infections due to COVID-19 in children. Time: Baseline-Day 60Description: Pearson or Spearman's correlation of clinical risk factors such as age, underlying diagnosis, immunosuppression with outcomes as detailed in primary objective 1 will be evaluated.
Measure: Clinical risk factors of acute respiratory infection due to COVID-19 in children. Time: Baseline-day 60Description: Immunological (e.g., Absolute lymphocyte/monocyte counts, Immunoglobulin level) and serological (antibodies against the virus) response measures will be summarized with mean, standard deviation, median and range.
Measure: Immunologic response to acute respiratory infection due to COVID-19 in children. Time: Baseline-day 60Description: The duration of viral shedding, defined as the time between the first positive test date and the first negative test date, will be summarized for all participants with mean, standard deviation, median and range.
Measure: Duration of viral shedding and evolution in children longitudinally. Time: Baseline-Day 60COHIVE is an observational cohort nested in four antiretroviral therapy research studies (ADVANCE - NCT03122262; D²EFT - NCT03017872; DolPHIN2 - NCT03249181 and NAMSAL-ANRS12313 - NCT02777229). COHIVE will include participants who are possible COVID-19 cases with symptoms or confirmed COVID-19 cases, and participants who agree to have a serology testing for SARS-CoV-2 regardless of COVID-19 history.
Description: To characterise the clinical features of symptomatic COVID-19 in PLWH (cardio-respiratory and other clinical signs or symptoms), described overall and by HIV and comorbid disease factors including pregnancy status.
Measure: Clinical features of symptomatic COVID-19 in people living with HIV (PLWH) Time: At baselineDescription: To characterise the clinical outcomes of symptomatic COVID-19 in PLWH, assessing the outcomes of patients including the percentage of patients who are fully recovered, required hospitalisation, developed severe illness (ICU admission or equivalent) or died.
Measure: Clinical outcomes of symptomatic COVID-19 in PLWH Time: At Day 28Description: To characterise the clinical outcomes of symptomatic COVID-19 in PLWH, assessing the outcomes of patients including the percentage of patients who are fully recovered, required hospitalisation, developed severe illness (ICU admission or equivalent) or died.
Measure: Clinical outcomes of symptomatic COVID-19 in PLWH Time: At Month 3Description: To determine seroprevalence of COVID-19 in all parent study participants regardless of COVID-19 history.
Measure: Seroprevalence of COVID-19 in all parent study participants Time: Through study completion, an average of one yearThis is a single arm phase II trial to assess efficacy and confirm safety of infusions of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms,with or without confirmed interstitial COVID-19 pneumonia by chest Xray or CT. A total of 29 eligible subjects will be enrolled to receive anti-SARS-CoV-2 plasma.Outcomes will be compared to hospitalized controls with confirmed COVID-19 disease through retrospective chart review.
Description: Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.
Measure: Transfer to ICU Time: Days 0 - 60Description: Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.
Measure: 28 day mortality Time: Days 0 - 60Description: Will be collected from time of enrollment until completion of the study. The adverse events will be evaluated by CTCAE V5.0 and MedDRA.
Measure: Cumulative incidence of serious adverse events Time: Days 0 - 60Description: Will be done by collecting respiratory tract swabs and testing for SARS-CoV-2 positivity.
Measure: Rates and duration of SARS-CoV-2 Time: Days 0, 7, 14, and 21Description: Serum or plasma will be collected and analyzed for SARS-CoV-2 antibody.
Measure: Serum of plasma antibody titer to SARS-CoV-2 Time: Days 0, 7, 14, and 28Description: Blood will be collected and analyzed for cellular and humoral response.
Measure: Cellular and humoral immune response Time: Days 0, 7, 14, 28Description: All days where a supplemental oxygen is needed will be recorded as a concomitant medication and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the supplemental oxygen free days.
Measure: Supplemental oxygen free days Time: Days 0-28Description: All days where a ventilator is needed will be recorded as a concomitant procedure and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ventilator free days.
Measure: Ventilator free days Time: Days 0 - 28Description: All days where the participant is admitted to the ICU will be recorded and subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ICU free days.
Measure: ICU free days Time: Days 0 - 28Description: The patient will be evaluated throughout their enrollment in the study. The score will be evaluated to see if the score improved or worsened throughout their admission.
Measure: Sequential organ failure assessment score Time: days 0, 1, 4, 7, 14, 21, 28Description: Concomitant medications will be recorded throughout the patients participation in the study and vasopressors will be recorded, if they are needed.
Measure: Need for vasopressors Time: Days 0 - 60Description: Renal function will be assessed throughout the patients participation in the study. If renal replacement therapy is needed, it will be captured as a concomitant procedure.
Measure: Need for renal replacement therapy Time: Days 0 - 60Description: Respiratory function will be assessed throughout the patients participation in the study. If ECMO is needed, it will be captured as a concomitant procedure.
Measure: Need for extracorporeal membrane oxygenation (ECMO) Time: Days 0 - 60Description: Will be calculated from the date the patient entered the hospital until they were discharged.
Measure: Hospital length of stay (LOS) Time: Days 0-60Description: Will be calculated from the date the patient entered the ICU until they were discharged from the ICU.
Measure: ICU LOS Time: days 0 - 60Description: All adverse events will be recorded and evaluated by CTCAE v.5.0. All grade 3 and 4 AEs will be calculated to determine safety of convalescent plasma.
Measure: Grade 3 or 4 Adverse Events (AEs) Time: days 0 - 60This study aims to observe the long-term health-related quality of life (HRQOL) and physical performance in individuals hospitalized due to a COVID-19 infection. Therefore, data is extracted from a study-site standard aftercare program which has been adjusted for this patient population. This comprehensive aftercare program includes education sessions and physical exercise. A second aim is to observe adherence and feasibility to the program and if indicated compare the clinical data and outcomes from patients following the program with patients denying to participate in guided exercise and education sessions. It is expected that patients hospitalized due to COVID-19 infection show a reduction in physical performance and HRQOL directly after discharge. The severity of illness is hypothesized to be associated with a reduction as well in HRQOL and physical performance after one-year post-discharge.
Description: Self-managed questionnaire on functional status, anxiety, pain and independence in daily living; The EuroQoL includes a five item scale and a visual analog scale from 0-100 in order to quantify perception of current health. The five item scale includes ordinary scores from 0-5. Lower numbers equal less problems and better quality of life. For the visual analog scale a higher number represents a better health status perceived.
Measure: Health-related quality of life; EuroQoL (EQ-5D-5L) Time: 01.04.2020 - 30.05.2021Description: 6-minute walk test measures the distance acquired during six minutes walking, it quantifies the physical performance, dyspnoea and endurance.
Measure: 6-minute walk test Time: 01.04.2020 - 30.05.2021Description: Measures the handgrip strength and is associated with sarcopenia, mortality and independence in life (e.g. for older individuals and patients after or with critical illness)
Measure: Jamar dynamometer Time: 01.04.2020 - 30.05.2021Description: Self-administered questionnaire on anxiety and depression after hospitalization; bot, anxiety and depression is quantified by an ordinal scale from 0-3, respectively. The lower the number the less signs of depression or anxiety are present.
Measure: Hospital Anxiety and Depression Scale (HADS) Time: 01.04.2020 - 30.05.2021Description: Questionnaire on avoidance, intrusion and arousal (or overreaction) in order to identify potential risk for post-traumatic stress. The Scale includes 22 questions ordinally scored from "not at all" to " very frequent" with four scores. The scores are transformed into numbers (0,1,3,5). The values are put in a formula resulting in a single value.A value below zero indicates no risk of post-traumatic stress disorder (PTSD) is present. Values equal or higher than zero indicate the risk of a PTSD
Measure: revised Impact of Event Scale (IES-R) Time: 01.04.2020 - 30.05.2020Description: Questionnaire on the nutritional condition of the patient. It includes 16 questions and 2 measures. Points range from 0-30; A score <17 indicates malnutirtion, a score from 17-23.5 indicates a risk of malnutrition and scores between 24-30 indicate normal nutritional behaviour.
Measure: Mini-Nutritional Assessment (MNA) Time: 01.04.2020 - 30.05.2021Description: Measures the lung function (bedside screening)
Measure: Spirometry (bed-side) Time: 01.04.2020 - 30.05.2021Description: This scale measures the functional state and Independence of patients after COVID-19 infection. The scale includes two items scored from 0-4 and 0-5. A high value indicates more restrictions in function and independence during daily life.
Measure: Post-Covid Functional Scale (PCFS) Time: 01.04.2020 - 30.05.2021Description: Quantifies and stratifies the perception of dyspnoea with a score ranging from 0-4. The higher the value the more frequent and more severe is the perception of dyspnoea during daily life activities.
Measure: modified Medical Research Council Dyspnoea Scale (mMRC Dyspnoea) Time: 01.04.2020 - 30.05.2021This is a prospective study, involving contacting potential plasma donors and the use of their plasma to help fight off infections of those suffering from COVID19 in accordance to collection guidelines for plasma and FDA IND requirement. This study will include up to 240 participants potentially receiving convalescent plasma and up to 1000 potential donors. There are 3 basic arms to the study: mild, moderate and severe/critical severity. All 3 severity groups are eligible for enrollment, but mild severity will not be given plasma unless there is progression. Moderate severity will given up to 1 unit of plasma and severe/critical severity up to 2 units. There is no placebo group, however given the excepted issues of shortages of plasma, intention to treat will be used for analysis.
Description: Time it takes to identify eligible donors whom are willing to donate
Measure: Plasma Donor Time: Measured in days for 365 daysDescription: Time it takes the plasma collection center to contact willing donors whom are allowed to donate plasma
Measure: Plasma Donor Time: Measured in days for 365 daysDescription: Time from consent to infusion
Measure: Plasma Recipient Time: Measured evey 24 hours up to 30 daysDescription: Survival
Measure: Plasma Recipient Time: Measured in days with 30 day from discharge follow-upDescription: Time until plasma is donated
Measure: Plasma Donor Time: Measured every 24 hours up to 1 yearDescription: Incident of treatment-Emergent Adverse Events [Safety and Tolerability]
Measure: Plasma Recipient Time: Day 1, 2, 3, 4, 7, and 30 dayDescription: Morbidity reduction
Measure: Plasma Recipient Time: Day 1, 2, 3, 4, 7, and 30 dayDescription: Reduced Length of Stay in hospital
Measure: Plasma Recipient Time: Measured every 24 hours until patient discharged from hospital up to 1 yearDescription: Reduced Length of Stay on Advance Respiratory Support
Measure: Plasma Recipient Time: Measured every 24 hours until Off Advanced Respiratory Support up to 1 yearThe new Severe acute respiratory syndrome coronavirus (SARS-CoV-2) named coronavirus disease 2019 (COVID-19) is currently responsible for a pandemic spread of febrile respiratory infections, responsible for a veritable global health crisis. In adults, several evolutionary patterns are observed: i) a/pauci-symptomatic forms; ii) severe forms immediately linked to rare extensive viral pneumonia; and iii) forms of moderate severity, some of which progress to secondary aggravation (Day 7-Day 10). Children can be affected, but are more rarely symptomatic and severe pediatric forms are exceptional. Like some other coronaviruses (SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV)), these differences in clinical expression could be based on a variability in the immunological response, notably either via inhibition of the type I interferon (IFN-I) response, or on the contrary an immunological dysregulation responsible for a "cytokine storm" associated with the aggravation. Little is known about the impact of these innate immune response abnormalities on the adaptive response. In addition, certain genetic factors predisposing to a state of "hyper-fragility" and certain viral virulence factors could also be predictive of the clinical response. In this context, the main hypothesis is that the virological analysis and the initial biological and immunological profiles are correlated with the initial clinical presentation of COVID-19 infection. In particular, children forms and pauci-symptomatic disease in adults may be linked to a more robust innate immune response, including better production of IFN-I.
Description: Describe the immune response (biological profile in blood samples) of children and adults with COVID-19 infection and correlate it with the initial clinical presentation measurement of the following parameters in blood at time of inclusion: white blood cell count, C-reactive protein, procalcitonin, hepatic and renal functions, ferritin, vitamin C and D, fibrinogen, prothrombin time test and partial thromboplastin time in order to correlate them with the initial clinical presentation.
Measure: Initial biological profile of children and adults with COVID-19 infection Time: Day 0Description: measurement of the following parameters in blood at time of inclusion: interferon alpha and gamma, Tumor necrosis factor (TNF) alpha, interleukins 6 and 10, transcriptomic signature of interferon, lymphocyte phenotyping and monocyte Human Leukocyte Antigen - DR isotype (HLA-DR) expression in order to correlate them with the initial clinical presentation.
Measure: Initial immunological profile of children and adults with COVID-19 infection Time: Day 0Description: Determine whether the initial biological and immunological profiles (see primary outcome measures) are predictive of a secondary worsening (i.e., admission to intensive care unit, and/or increase in NEWS-2 score, and/or increase in oxygen dependence level) of COVID-19 infection
Measure: Clinical worsening Time: Within 21 days following inclusionDescription: measurement of the following parameters in blood at day 7, and at time of worsening: interferon alpha and gamma, TNF alpha, interleukins 6 and 10, transcriptomic signature of interferon, lymphocyte phenotyping and monocyte HLA-DR expression in order to correlate them with with the secondary worsening
Measure: Evolution of the immunological profile of children and adults with COVID-19 Time: Within 21 days following inclusionDescription: Nasopharyngeal swabs SARS-CoV-2 viral loads (copies/mL) measured at day 0 and correlation to the initial clinical presentation
Measure: Nasopharyngeal swabs SARS-CoV-2 viral loads of children and adults with COVID-19 Time: Day 0Description: Serological SARS-CoV-2 results (titers in specific Immunoglobulin G (IgG) antibodies) measured at day 0 and correlation to the initial clinical presentation
Measure: titers in specific Immunoglobulin G (IgG) antibodies of children and adults with COVID-19 Time: Day 0Description: Serological SARS-CoV-2 results (titers in specific Immunoglobulin M (IgM) antibodies) measured at day 0 and correlation to the initial clinical presentation
Measure: titers in specific Immunoglobulin M (IgM) antibodies of children and adults with COVID-19 Time: Day 0Description: Nasopharyngeal swabs SARS-CoV-2 viral loads (copies/mL) measured within 21 days following inclusion, and correlation to the secondary worsening
Measure: Nasopharyngeal swabs SARS-CoV-2 viral loads of children and adults with COVID-19 Time: Within 21 days following inclusionDescription: Serological SARS-CoV-2 results (titers in specific Immunoglobulin G (IgG) antibodies) measured within 21 days following inclusion, and correlation to the secondary worsening
Measure: titers in specific Immunoglobulin G (IgG) antibodies of children and adults with COVID-19 Time: Within 21 days following inclusionDescription: Serological SARS-CoV-2 results (titers in specific Immunoglobulin M (IgM) antibodies) measured within 21 days following inclusion, and correlation to the secondary worsening
Measure: titers in specific Immunoglobulin G (IgM) antibodies of children and adults with COVID-19 Time: Within 21 days following inclusionDescription: Genotyping using the whole exome sequencing technic (by Illumina HiSEQ 2500) in order to correlate with the initial clinical presentation.
Measure: Genetic profile of adults with COVID-19 infection Time: Day 0Description: Genotyping using the whole exome sequencing technic (Illumina HiSEQ 2500) in order to correlate with with the secondary worsening
Measure: Genetic profile of adults with COVID-19 infection Time: Within 21 days following inclusionThis is a PET/CT study using the 18F-αvβ6-binding-peptide.The goal of this study is to evaluate this peptide in patients after infection with SARS CoV2.
Description: Completion of administration of 18F-αvβ6-BP in SARC CoV2 patients
Measure: Administration of 18F-αvβ6-BP Time: baselineDescription: Completion of administration of 18F-αvβ6-BP in SARC CoV2 patients
Measure: Administration of 18F-αvβ6-BP Time: 3 monthsDescription: Completion of administration of 18F-αvβ6-BP in SARC CoV2 patients
Measure: Administration of 18F-αvβ6-BP Time: 6 monthsDescription: Uptake of 18F-αvβ6-BP in lung damage will be measured by PET
Measure: Determine whether 18F-αvβ6-BP demonstrates accumulation in lung damage Time: baselineDescription: Uptake of 18F-αvβ6-BP in lung damage will be measured by PET
Measure: Determine whether 18F-αvβ6-BP demonstrates accumulation in lung damage Time: 3 monthsDescription: Uptake of 18F-αvβ6-BP in lung damage will be measured by PET
Measure: Determine whether 18F-αvβ6-BP demonstrates accumulation in lung damage Time: 6 monthsDescription: Uptake of 18F-αvβ6-BP in lung measured by PET will be compared to lung damage as indicated on CT.
Measure: Determine whether 18F-αvβ6-BP accumulation in lung correlates to lung damage as indicated on CT. Time: baselineDescription: Uptake of 18F-αvβ6-BP in lung measured by PET will be compared to lung damage as indicated on CT.
Measure: Determine whether 18F-αvβ6-BP accumulation in lung correlates to lung damage as indicated on CT. Time: 3 monthsDescription: Uptake of 18F-αvβ6-BP in lung measured by PET will be compared to lung damage as indicated on CT.
Measure: Determine whether 18F-αvβ6-BP accumulation in lung correlates to lung damage as indicated on CT. Time: 6 monthsA multicenter randomized clinical trial aiming to assess the efficacy of hydroxychloroquine associated to Zinc compared to hydroxychloroquine, in the prevention of Military Health Professionals Exposed to SARS CoV2 in Tunisia
Description: Frequency of confirmed SARS CoV2 infection
Measure: SARS CoV2 infection Time: At 2 months of follow-upDescription: Any COVID-19 related symptoms (cough, fever, headache, vomiting, nausea, dyspnea, diarrhea, smell disorder,conjunctivitis, dizziness)
Measure: COVID-19 symptoms description Time: At 2 months of follow-upDescription: Any adverse event or serious adverse event
Measure: Adverse Events Time: each month up to 2 monthsThe study of volatile organic compounds (VOCs) detected in exhaled air is an innovative research area for respiratory diseases. This analysis can be done by the technique of electronic nose, simpler and faster, which provides an idea of the general profile of the VOCs without identifying them. The VOCs in exhaled air in patients hospitalized for COVID-19 infection are analysed in this study, using electronic noses.
Description: Comparison of variation of profiles of Volatile Organic Compounds in exhaled air from electronic noses (a set of sensors interacting with the VOCs exhaled. The analysis of the generated signal (resistance or load variations) is characteristic of the composition of VOCs), between patients who improve and patients who get worse during their hospitalisation for COVID-19 infection
Measure: Profiles of volatile organic compounds (VOCs) in exhaled air between 2 health conditions Time: 1 dayDescription: Comparison of variation of profiles of Volatile Organic Compounds in exhaled air from electronic noses (a set of sensors interacting with the VOCs exhaled. The analysis of the generated signal (resistance or load variations) is characteristic of the composition of VOCs), between the start and the discharge to the hospital in patients infecting and recovering from COVID-19.
Measure: Profiles of volatil organic compounds (VOCs) in exhaled air on 1 health condition Time: 2 weeksDescription: Comparison of variation of profiles of Volatile Organic Compounds in exhaled air from electronic noses (a set of sensors interacting with the VOCs exhaled. The analysis of the generated signal (resistance or load variations) is characteristic of the composition of VOCs), between the hospitalisation period and a post-hospitalisation follow-up consultation in patients infected by COVID-19 and recovered.
Measure: Profiles of volatil organic compounds (VOCs) in exhaled air between 2 periods Time: 4 monthsThe SARS-CoV-2 epidemic was declared as a global pandemic by the WHO on March 12, 2020. France is affected with approximately 120,000 biologically confirmed cases, as of April 30, 2020, a figure probably very underestimated. Its distribution in different populations, in particular immunocompromised, has not yet been measured. The in vitro efficacy of lopinavir coupled with ritonavir, an HIV protease inhibitor, on SARS-CoV, responsible for SARS has been discussed and this therapeutic combination is currently being evaluated in patients infected with COVID-19. The possible protective role of treatment with Lopinavir / ritonavir or another HIV protease inhibitor has not been studied. In addition, patients receiving HIV pre-exposure prophylaxis (PrEP) share certain epidemiological and behavioral characteristics with HIV-infected patients. The objective was to carry out an epidemiological study aimed at determining the attack rate of COVID-19 infection in patients infected with HIV and or on PrEP and to analyze this attack rate according to the characteristics of these 2 populations and in particular the existence or not of an antiretroviral treatment comprising Lopinavir / Ritonavir or another inhibitor of the HIV protease. Cross-referencing of Virology Laboratory data (positive or negative screening) and clinical-biological data can be easily carried out using a unique identification number in the 2 software programs and will allow an almost exhaustive epidemiological analysis in 2 well identified populations.
Description: Cross-referencing of Virology Laboratory data (positive or negative screening) and clinical-biological data using the unique identification number in the 2 databases. This cross-checking of files will allow an almost exhaustive epidemiological analysis in 2 well identified populations.
Measure: Covid attack rate Time: During hospitalisation for Covid symptoms: one week (max 2 weeks) after symptoms initiationMain goal: To generate information on the efficacy and safety of Dialyzable Leukocyte Extract (DLE) as an aid in the treatment of patients with acute respiratory infection (suspected or confirmed cases of COVID-19). Primary goal: To generate information on the efficacy of DLE as an aid in symptomatic treatment, by reducing the signs and symptoms of acute respiratory infection (suspected/confirmed cases of COVID-19). Secondary goals: 1. To evaluate clinical deterioration and respiratory alarm data. 2. To evaluate the duration of the clinical picture. 3. To explore cytokine changes associated with the therapeutic effect induced by DLE. 4. To obtain data on the safety of DLE as an aid in the symptomatic treatment of acute respiratory infection (suspected/confirmed cases of COVID-19). 5. To generate information to validate the contingency scale to assess the severity of acute respiratory disease (suspected/confirmed cases of COVID-19). Justification The systemic inflammatory response has been recognized as being responsible for COVID-19 complications. Immunomodulation strategies to control it are currently being considered, including the use of systemic steroids to down-regulate the systemic inflammatory response, the use of human immunoglobulin and even chloroquine given its anti-inflammatory and antiviral qualities; however, none of these treatments has been sufficiently studied or has shown any significant change in the clinical course of infected patients. Due to the importance of the COVID-19 pandemic and in the absence of specific treatment, it is important to implement new treatments that allow modulating the immune response, and one strategy may be the addition of DLE to symptomatic and supportive treatment. Hypotheses by goals. 1. The addition of DLE to the symptomatic treatment could decrease the severity of the clinical outcome (signs and symptoms) in individuals with an acute respiratory infection (cases suspected/confirmed by COVID-19). 2. The addition of DLE to the symptomatic treatment could decrease the clinical deterioration due to the acute respiratory infectious process (suspected/confirmed cases of COVID-19). 3. The addition of DLE to the symptomatic treatment could decrease the duration of the clinical outcome (suspected/confirmed cases of COVID-19).
Description: Change in the score of the "Contingency scale to assess the severity of acute respiratory disease in cases suspected/confirmed by COVID-19" at the end of treatment concerning the baseline value. The clinical effect will be daily evaluated with the patient's diary in the cell app. Minimum value 0, Maximum value 32 points. Higher scores mean worse outcome.
Measure: Change in the score of the "Contingency scale to assess the severity of acute respiratory disease in cases suspected/confirmed by COVID-19" Time: 35 daysDescription: Defined as the presence of signs and symptoms related with respiratory alarm symptoms. The respiratory alarm data will be daily evaluated with the patient's diary in the cell app.
Measure: Clinical deterioration Time: 35 daysDescription: Defined as the number of days with any of the symptoms mentioned in contingency table during the visits and follow-up through the patient's diary in the cell app.
Measure: Duration of the clinical status Time: 35 daysDescription: Defined as the changes in the total concentration of the serum cytokines IL-6, TNF-α and type I and II Interferons due to DLE treatment.
Measure: Cytokine concentration Time: 35 daysThis phase I/IIa trial studies the side effects of rintatolimod and interferon (IFN) alpha-2b in treating cancer patients with mild or moderate COVID-19 infection. Interferon alpha is a protein important for defense against viruses. It activates immune responses that help to clear viral infection. Rintatolimod is double stranded ribonucleic acid (RNA) designed to mimic viral infection by stimulating immune pathways that are normally activated during viral infection. Giving rintatolimod and interferon alpha-2b may activate the immune system to limit the replication and spread of the virus.
Description: This refers to the frequency of grade 3 or 4 AEs considered to be probably or definitely related to the treatment regimen. Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE version [v] 5.0).
Measure: Incidence of adverse events (AEs) Time: Up to 30 days post treatment intiationDescription: ARDS will be defined by Berlin criteria.
Measure: Reduction of acute respiratory distress syndrome (ARDS) Time: Up to 30 days post treatment initiationDescription: The binary endpoint of 30-day mortality will be analyzed using a logistic regression model.
Measure: 30-day mortality Time: At 30 days post treatment initiationDescription: Will be analyzed using quantitative polymerase chain reaction (PCR).
Measure: Kinetics of viral load in the peripheral blood and nasal swabs Time: During the course of treatment up to day 28Description: The circulatory inflammatory mediators include C-reactive protein (CRP), cytokines, chemokines, interferons.
Measure: Kinetics of changes of the immune subsets and circulating inflammatory mediators in peripheral blood Time: During the course of treatment up to day 28The trial has two parts: a dose-finding part (Part A) with four dose cohorts (treatment groups) for each vaccine and one pre-defined and one optional dose level for a de-escalation approach and, a second part (Part B) dedicated to recruit expansion cohorts with dose levels which are selected from data generated in Part A. The vaccines BNT162a1, BNT162b1, and BNT162b2 will be administered using a Prime/Boost (P/B) regimen. The vaccine BNT162c2 will be administered using a Single dose (SD) regimen.
Description: For BNT162a1, BNT162b1, BNT162b2 (P/B): occurring up to 21±2 days after the prime immunization.
Measure: The proportion of subjects with at least 1 unsolicited treatment emergent adverse event (TEAE): Time: 21 days following dose administrationDescription: For BNT162a1, BNT162b1, BNT162b2 (P/B): occurring up to 28±4 days after the boost immunization. For BNT162c2 (SD): The proportion of subjects with at least 1 unsolicited TEAE occurring up to 28±4 days after the immunization.
Measure: The proportion of subjects with at least 1 unsolicited treatment emergent adverse event (TEAE): Time: 28 days following dose administrationDescription: Functional antibody responses at 7±1 days and 21±2 days after primary immunization and at 21±2 days, 63±5 days, and 162±7 days after the boost immunization.
Measure: For BNT162a1, BNT162b1, BNT162b2 (P/B): Time: up to 162 days following dose administrationDescription: Fold increase in functional antibody titers 7±1 days and 21±2 days after primary immunization and at 21±2 days, 63±5 days, and 162±7 days after the boost immunization.
Measure: For BNT162a1, BNT162b1, BNT162b2 (P/B): Time: up to 162 days following dose administrationDescription: Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline at 7±1 days and 21±2 days after primary immunization and at 21±2 days, 63±5 days, and 162±7 days after the boost immunization.
Measure: For BNT162a1, BNT162b1, BNT162b2 (P/B): Time: up to 162 days following dose administrationDescription: Functional antibody responses at 7±1 days, 21±2 days, 42±3 days, 84±5 days, and 183±7 days after the primary immunization.
Measure: For BNT162c2 (SD): Time: up to 183 days following dose administrationDescription: Fold increase in functional antibody titers at 7±1 days, 21±2 days, 42±3 days, 84±5 days, and 183±7 days after the primary immunization.
Measure: For BNT162c2 (SD): Time: up to 183 days following dose administrationDescription: Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline at 7±1 days, 21±2 days, 42±3 days, 84±5 days, and 183±7 days after the primary immunization.
Measure: For BNT162c2 (SD): Time: up to 183 days following dose administrationThe purpose of the study is to design and execute a prospective, longitudinal, descriptive cohort study in a pragmatic clinical practice for adults with symptoms that may be related to COVID-19.
Description: Patient reported change
Measure: Patient reported main complaint Time: 24 hoursDescription: Patient reported change
Measure: Patient reported main complaint Time: 48 hoursDescription: Patient reported change
Measure: Patient reported main complaint Time: 3 monthsDescription: Patient reported change
Measure: Patient reported main complaint Time: 12 monthsDescription: Patient interview notes as written by clinicians.
Measure: Conduct qualitative analyses of data Time: 24 hoursDescription: Patient interview notes as written by clinicians.
Measure: Conduct qualitative analyses of data Time: 48 hoursDescription: Patient interview notes as written by clinicians.
Measure: Conduct qualitative analyses of data Time: 3 monthsDescription: Patient interview notes as written by clinicians.
Measure: Conduct qualitative analyses of data Time: 12 monthsIn this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.
Description: Number of participants alive at day 28.
Measure: Patient Survival Time: 28 daysDescription: Number of participants alive at day 60, end of study.
Measure: Patient Survival Time: 60 daysRandomized open label clinical trial carried out at study centers in Sweden, including Karolinska University Hospital Huddinge, S:t Göran Hospital, Danderyd Hospital and Västmanlands Hospital. Patients with COVID-19 who are hospitalized with oxygen therapy are eligible for inclusion. Subjects are randomized to 14 days of inhalation with ciclesonide 360 µg twice daily or to standard of care. Primary outcome is time (in days) of received supplemental oxygen therapy. Key secondary outcome is a composite outcome of death and received invasive mechanical ventilation within 30 days.
Description: Time (in days) of received supplemental oxygen therapy (defined as being alive and discharged from hospital to home or at least 48 h of not receiving oxygen therapy during hospitalization).
Measure: Duration of received supplemental oxygen therapy Time: 30 days after study inclusionDescription: Rate of and time to (in days) received invasive mechanical ventilation or all-cause death
Measure: Invasive mechanical ventilation or all-cause death Time: 30 days after study inclusionDescription: Rate of and time to (in days) death of any cause
Measure: All cause death Time: 30 days after study inclusionDescription: Rate of and time to (in days) received invasive mechanical ventilation
Measure: Invasive mechanical ventilation Time: 30 days after study inclusionDescription: Maximum received oxygen therapy during hospitalization in liters per minute
Measure: Maximum oxygen therapy Time: 30 days after study inclusionDescription: Time (in days) from study inclusion to discharge from hospital.
Measure: Duration of hospitalization Time: 30 days after study inclusionDescription: Level of remaining dyspnea symptoms according to the Modified Medical Research Council Dyspnea Scale
Measure: Remaining dyspnea symptoms Time: 3 and 6 months after inclusion. (Only for patients hospitalized at S:t Goran's Hospital)Agent Name and Study Duration ArtemiC is a medical spray comprised of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (=Boswellia) (15 mg/ml) and vitamin C (60 mg/ml) in micellar formulation for spray administration. Patients will receive up to 6 mg Artemisinin, 20 mg Curcumin, 15 mg Frankincense and 60 mg vitamin C given daily as an add-on therapy (in addition to standard care) in two divided doses, on Days 1 and 2. Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care. Patient follow-up will last 2 weeks. During this time, patients will be monitored for adverse events. Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy. Placebo, composed of the same solvent but without active ingredients, will be given in the placebo group as add-on therapy, 2 times a day, on Days 1 and 2. Overall rationale A preparation of ArtemiC, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus SARS-CoV-2. It is readily available in light of its status as a food supplement. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed. Leading among these considerations are well established immuno-modulatory activities of the active ingredients as established in vitro and in vivo and published over the years. These activities as apparent, for example, in diminishing activity of TNF alpha and IL-6 levels are acknowledged to be relevant to the pathophysiology processes involved in the progressive form of COVID-19. The active agents have in addition prominent anti-oxidant, anti-inflammatory as well as anti-aggregant and anti-microbial activities. Based on these activities and observations in animal models, together with clinical experience of the separate ingredients and in various combinations in other contexts it is proposed to evaluate their effect in the context of COVID-19. Study Purpose This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19. Methodology 50 adult patients who suffer from COVID-19 infection studied in parallel groups treated with active agent or placebo as add on to standard care. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.
Description: patient will be assessed using a scoring table for changes in clinical signs
Measure: Time to clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of = 2 Maintained for 24 Hours in comparison to routine treatment Time: 24 hoursDescription: Adverse events caused by the study drug will be assessed
Measure: Percentage of participants with definite or probable drug related adverse events Time: 14 daysA weekly questionnaire is sent to patients and parents of patients who are vulnerable for infections. Possible symptoms of COVID19 are asked for and use of healthcare services and testing for COVID19. Weekly reports are being send to the national institutions to update advice given to this group.
Description: To describe frequency of cough, fever, diarrhoea, shortness of breath, sore throat, blocked nose, red eyes, headache, joint pain, muscle pain, fatigue, chills, nausea, vomiting, diarrhoea over a year
Measure: To describe COVID19 infection in children/adults who are vulnerable for infection in an outpatients setting Time: 1 yearDescription: Patient/parent reported positive tests for COVID19
Measure: Number of children/adults tested positive for COVID19 Time: 1 yearDescription: Patient/parent reported admissions in hospital because of COVID19
Measure: Number of children/adults admitted in hospital because of COVID19 Time: 1 yearDescription: Patient/parent reported effect of COVID19 on daily activities
Measure: To assess the impact of COVID19 infection on the daily activities of immunosuppressed adults and children Time: 1 yearThe primary objective of this study is to evaluate if the addition of zanubrutinib to supportive care increases the respiratory failure-free survival rate at Day 28 in participants hospitalized for Corona Virus Disease 2019 (COVID-19) and pulmonary distress.
Description: Respiratory failure-free survival rate 28 is defined as the proportion of patients who have not had respiratory failure nor died <= 28 days from randomization.
Measure: Respiratory failure-free survival rate at day 28 Time: 28 DaysDescription: This scale evaluates the safety and efficacy of investigational therapeutic agents in combination with care for the treatment of hospitalized participants suffering from COVID-19 infections on a scale of scores from 0 to 8, with higher scores indicating higher level of severity of the disease. (0 = No clinical or virological evidence of disease, and 8 = Death)
Measure: Change from Baseline to Day 14 in WHO - 8 Point Ordinal Scale Time: Up to 28 DaysObservational, cross-sectional, multi-center, multi-wave survey, assessing characteristics and predictors of physical and mental health as well as health behaviors during COVID-19 pandemic, targeting the general population (children, adolescents and adults).
Description: Primary outcome in the wave 1 survey, conducted during the COVID-19 pandemic, will be mean change in visual analogue scale-assessed transdiagnostic measures across all psychiatric symptoms, and World Health Organization (WHO)-5 well-being in the last 2 weeks compared to the last 2 weeks of "regular life" before the COVID-19 outbreak. For WHO-5 the raw score ranges from 0 (absence of well-being) to 25 (maximal well-being).
Measure: Mental health symptoms, well-being change from last 2 weeks before the pandemic to last 2 weeks during COVID-19 pandemic Time: wave 1 - change from last 2 weeks before pandemic to the following from April 26th 2020 on, until the pandemic will be over as declared by WHO (we estimate between October 2020 and April 2021)Description: Primary outcome in the wave 2 survey, conducted during the COVID-19 pandemic, will be mean change in visual analogue scale-assessed transdiagnostic measures across all psychiatric symptoms and World Health Organization (WHO)-5 well-being in the last 2 weeks six months after the COVID-19 pandemic ended, compared to the last 2 weeks of "regular life" before the COVID-19 outbreak. For WHO-5 the raw score ranges from 0 (absence of well-being) to 25 (maximal well-being).
Measure: Mental health symptoms, well-being change from last 2 weeks before the pandemic to last 2 weeks 6 months after WHO declares pandemic over COVID-19 pandemic Time: wave 2 - change from before to 6 months after pandemicDescription: Primary outcome in the wave 3 survey, conducted during the COVID-19 pandemic, will be mean change in visual analogue scale-assessed transdiagnostic measures across all psychiatric symptoms and World Health Organization (WHO)-5 well-being in the last 2 weeks 12 months after the COVID-19 pandemic ended, compared to the last 2 weeks of "regular life" before the COVID-19 outbreak. For WHO-5 the raw score ranges from 0 (absence of well-being) to 25 (maximal well-being).
Measure: Mental health symptoms change, well-being change from last 2 weeks before the pandemic to last 2 weeks 12 months after WHO declares pandemic over COVID-19 pandemic Time: wave 3 - change from before to 12 months after pandemic (after the pandemic outbreak has been declared from WHO, and until the pandemic outbreak has been declared conlucded by WHO)Description: Change in alcohol abuse, as change in units used from last 2 weeks before the pandemic to last 2 weeks during pandemic
Measure: Change in alcohol abuse, as change in units used from last 2 weeks before the pandemic to last 2 weeks during pandemic Time: wave 1 - change from last 2 weeks before pandemic to the following from April 26th 2020 on, until the pandemic will be over as declared by WHO (we estimate between October 2020 and April 2021)Description: Change in cigarettes use, as change in number of cigarettes per day from last 2 weeks before the pandemic to last 2 weeks during pandemic
Measure: Change in cigarettes use, as change in number of cigarettes per day from last 2 weeks before the pandemic to last 2 weeks during pandemic Time: wave 1 - change from last 2 weeks before pandemic to the following from April 26th 2020 on, until the pandemic will be over as declared by WHO (we estimate between October 2020 and April 2021)Description: Change in grams of cannabinoids smoked from last 2 weeks before the pandemic to last 2 weeks during pandemic
Measure: Change in grams of cannabinoids smoked from last 2 weeks before the pandemic to last 2 weeks during pandemic Time: wave 1 - change from last 2 weeks before pandemic to the following from April 26th 2020 on, until the pandemic will be over as declared by WHO (we estimate between October 2020 and April 2021)Description: Change in alcohol abuse, as change in units used from last 2 weeks before the pandemic to last 2 weeks during pandemic
Measure: Change in alcohol abuse, as change in units used from last 2 weeks before the pandemic to last 2 weeks during pandemic Time: wave 2 - change from before to 6 months after pandemicDescription: Change in cigarettes use, as change in number of cigarettes per day from last 2 weeks before the pandemic to last 2 weeks during pandemic
Measure: Change in cigarettes use, as change in number of cigarettes per day from last 2 weeks before the pandemic to last 2 weeks during pandemic Time: wave 2 - change from before to 6 months after pandemicDescription: Change in grams of cannabinoids smoked from last 2 weeks before the pandemic to last 2 weeks during pandemic
Measure: Change in grams of cannabinoids smoked from last 2 weeks before the pandemic to last 2 weeks during pandemic Time: wave 2 - change from before to 6 months after pandemicDescription: Change in alcohol abuse, as change in units used from last 2 weeks before the pandemic to last 2 weeks during pandemic
Measure: Change in alcohol abuse, as change in units used from last 2 weeks before the pandemic to last 2 weeks during pandemic Time: wave 3 - change from before to 12 months after pandemicDescription: Change in cigarettes use, as change in number of cigarettes per day from last 2 weeks before the pandemic to last 2 weeks during pandemic
Measure: Change in cigarettes use, as change in number of cigarettes per day from last 2 weeks before the pandemic to last 2 weeks during pandemic Time: wave 3 - change from before to 12 months after pandemicDescription: Change in grams of cannabinoids smoked from last 2 weeks before the pandemic to last 2 weeks during pandemic
Measure: Change in grams of cannabinoids smoked from last 2 weeks before the pandemic to last 2 weeks during pandemic Time: wave 3 - change from before to 12 months after pandemicDescription: Change in general physical health, self-rated, on a VAS scale from 0 to 100.
Measure: Change in general physical health, self-rated, on a VAS scale from 0 to 100. Time: wave 1 - change from last 2 weeks before pandemic to the following from April 26th 2020 on, until the pandemic will be over as declared by WHO (we estimate between October 2020 and April 2021)Description: Change in general physical health, self-rated, on a VAS scale from 0 to 100.
Measure: Change in general physical health, self-rated, on a VAS scale from 0 to 100. Time: wave 2 - change from before to 6 months after pandemicDescription: Change in general physical health, self-rated, on a VAS scale from 0 to 100.
Measure: Change in general physical health, self-rated, on a VAS scale from 0 to 100. Time: wave 3 - change from before to 12 months after pandemicDescription: Change in general mental health, self-rated, on a VAS scale from 0 to 100.
Measure: Change in general mental health, self-rated, on a VAS scale from 0 to 100. Time: wave 1 - change from last 2 weeks before pandemic to the following from April 26th 2020 on, until the pandemic will be over as declared by WHO (we estimate between October 2020 and April 2021)Description: Change in general mental health, self-rated, on a VAS scale from 0 to 100.
Measure: Change in general mental health, self-rated, on a VAS scale from 0 to 100. Time: wave 2 - change from before to 6 months after pandemicDescription: Change in general mental health, self-rated, on a VAS scale from 0 to 100.
Measure: Change in general mental health, self-rated, on a VAS scale from 0 to 100. Time: wave 3 - change from before to 12 months after pandemicDescription: Change in easiness of access to care, self-rated a on a VAS scale from 0 to 100.
Measure: Change in easiness of access to care, self-rated a on a VAS scale from 0 to 100. Time: wave 1 - change from last 2 weeks before pandemic to the following from April 26th 2020 on, until the pandemic will be over as declared by WHO (we estimate between October 2020 and April 2021)Description: Change in easiness of access to care, self-rated a on a VAS scale from 0 to 100.
Measure: Change in easiness of access to care, self-rated a on a VAS scale from 0 to 100. Time: wave 2 - change from before to 6 months after pandemicDescription: Change in easiness of access to care, self-rated a on a VAS scale from 0 to 100.
Measure: Change in easiness of access to care, self-rated a on a VAS scale from 0 to 100. Time: wave 3 - change from before to 12 months after pandemicDescription: Change in medication adherence, self-rated a on a VAS scale from 0 to 100.
Measure: Change in medication adherence, self-rated a on a VAS scale from 0 to 100. Time: wave 1 - change from last 2 weeks before pandemic to the following from April 26th 2020 on, until the pandemic will be over as declared by WHO (we estimate between October 2020 and April 2021)Description: Change in medication adherence, self-rated a on a VAS scale from 0 to 100.
Measure: Change in medication adherence, self-rated a on a VAS scale from 0 to 100. Time: wave 2 - change from before to 6 months after pandemicDescription: Change in medication adherence, self-rated a on a VAS scale from 0 to 100.
Measure: Change in medication adherence, self-rated a on a VAS scale from 0 to 100. Time: wave 3 - change from before to 12 months after pandemicDescription: Change in functioning in self-care, school/work, social, and family, self-rated a on a VAS scale from 0 to 100.
Measure: Change in functioning in self-care, school/work, social, and family, self-rated a on a VAS scale from 0 to 100. Time: wave 1 - change from last 2 weeks before pandemic to the following from April 26th 2020 on, until the pandemic will be over as declared by WHO (we estimate between October 2020 and April 2021)Description: Change in functioning in self-care, school/work, social, and family, self-rated a on a VAS scale from 0 to 100.
Measure: Change in functioning in self-care, school/work, social, and family, self-rated a on a VAS scale from 0 to 100. Time: wave 2 - change from before to 6 months after pandemicDescription: Change in functioning in self-care, school/work, social, and family, self-rated a on a VAS scale from 0 to 100.
Measure: Change in functioning in self-care, school/work, social, and family, self-rated a on a VAS scale from 0 to 100. Time: wave 3 - change from before to 12 months after pandemicPreparation of safe purified hyper immunoglobulins containing anti-Corona VS2 immunoglobulins from plasma collected from COVID19 convalescent patients to be used to: 1. To determine efficacy of COVID19 hyper immunoglobulins prepared from convalescent plasma using VIPS Mini-Pool IVIG medical device in the treatment of COVID19 2. To determine efficacy of anti-SARS-CoV-2 hyper immunoglobulins in the prevention of infection in high risk groups exposed to SARS-CoV-2 infection
Description: efficacy of COVID19 hyper immunoglobulins prepared from convalescent plasma using VIPS Mini-Pool IVIG medical device in the treatment of COVID19
Measure: Efficacy of COVID19 hyper immunoglobulins for patients Time: 2 weeksDescription: efficacy of anti-SARS-CoV-2 hyper immunoglobulins in the prevention of infection in high risk groups exposed to SARS-CoV-2 infection
Measure: Efficacy of COVID19 hyper immunoglobulins for high risk groups Time: 1 monthDescription: overall percentage of adverse events as hemolysis and anaphylaxis ,headache and other complains that occur during 72 hours of following infusion of anti-SARS-CoV-2 hyper immunoglobulins will be assessed by 1-vital sign 2-hemolysis by LDH and bilirubin level
Measure: Safety of anti-SARS-CoV-2 hyper immunoglobulins assessed by percentage of adverse events Time: 72 hoursIt has been suggested that ibuprofen might be associated with more severe cases of coronavirus infections, based on the observation that severe COVID cases had been exposed to ibuprofen, resulting in a warning by the French authorities. This was attributed to: 1. a suggestion that ibuprofen might upregulate ACE-2 thereby increasing the entrance of COVID-19 into the cells, 2. an analogy with bacterial soft-tissue infections where more severe infections on NSAIDs are attributed to an immune-depressive action of NSAIDs, or to belated treatment because of initial symptom suppression, 3. fever is a natural response to viral infection, and reduces virus activity: antipyretic activity might reduce natural defenses against viruses. However fever reduction in critically ill patients had no effect on survival. However, these assertions are unclear: upregulation of ACEII would increase the risk of infection, not necessarily its severity, and would only apply to the use of NSAIDs before the infection, i.e. chronic exposure. It would be irrelevant to the infection once the patients are infected, i.e., to symptomatic treatment of COVID-19 infection. Anti-inflammatory effect masking the early symptoms of bacterial infections resulting in later antibiotic or other treatment is not applicable: there is no treatment of the virus that might be affected by masking symptoms. Antipyretic effect increasing the risk or the severity of infection would apply equally to all antipyretic agents including paracetamol, which share the same mechanism of action for fever reduction. EMA remains prudent about this assertion In addition, excess reliance on paracetamol while discouraging the use of ibuprofen might increase the risk of hepatic injury from paracetamol overdose. Paracetamol is the prime drug associated with liver injury and transplantation, in voluntary and inadvertent overdose or even at normal doses. This might be increased by COVID-related liver function alterations. It is therefore proposed to conduct a case-control study in a cohort of patients admitted to hospital in France with COVID-19 infection.
Description: Describe medications including ibuprofen used prior to admission associated with worse infection in COVID-19 patients in France. Thanks to a questionnaire created for the study, with 5 questions on existing pathology, drugs administrated symptom onset and when, hospitalisation. Each questions have a multiple choice.
Measure: Describe medications used prior to admission associated with worse infection in COVID-19 patients in France. Time: At inclusion dayDescription: Quantify medications including ibuprofen used prior to admission associated with worse infection in COVID-19 patients in France. Thanks to a questionnaire created for the study, with 5 questions: existing pathology, drugs administrated symptoms onset and when, hospitalisation. Each questions have a multiple choice.
Measure: Quantify medications used prior to admission associated with worse infection in COVID-19 patients in France. Time: At inclusion dayDescription: Describe patient characteristics thanks to the same questionnaire.
Measure: Describe other patient characteristics with worse infection in COVID-19 patients in France. Time: At inclusion dayDescription: Quantify patient characteristics thanks to the same questionnaire.
Measure: Quantify other patient characteristics with worse infection in COVID-19 patients in France. Time: At inclusion dayThe Malaysian COVID-19 Anosmia Study is a nationwide multicentre observational study to investigate the prevalence and characteristics of olfactory and gustatory/taste disturbances in COVID-19 infection in Malaysia, and to evaluate the predictive value of screening for these symptoms in COVID-19 infection. This study consists of two phases: the first phase is a cross-sectional study and the second phase is a case-control study. The case-control study is described here (the cross-sectional study is described in a separate ClinicalTrials.gov record).
Description: In the patient-reported online questionnaire, subjects will be asked regarding whether they experienced symptoms of olfactory and/or taste disturbances
Measure: Presence or absence of olfactory and taste disturbances in study participants Time: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infectionDescription: The relationship between case & control status and each exposure variable will be estimated by odds ratios and their 95% confidence intervals using conditional logistic regression models.
Measure: Adjusted odds ratio of olfactory & taste disturbances in COVID-19 infection Time: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked regarding other symptoms they experienced when they were diagnosed with COVID-19/within the past 2 weeks of answering the questionnaire (e.g. headache, nasal congestion, fever, chills, cough, dyspnoea, gastrointestinal symptoms, eye & ear symptoms)
Measure: Clinical manifestations of study participants Time: 2 weeks prior to answering questionnaire/ prior to diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked regarding their pre-existing health conditions (for example, obesity, diabetes, hypertension, cardiac conditions, previous head trauma, chronic rhinosinusitis, etc.)
Measure: Other pre-existing health conditions Time: BaselineDescription: PPV reflects the probability that the presence of olfactory and taste disturbances will have a positive diagnosis of COVID-19. This is derived from dividing the number of patients with olfactory & taste disturbances with COVID-19 infection over the total number of patients with olfactory and taste disturbances, and multiplying by 100%
Measure: Positive predictive value (PPV) of olfactory and taste disturbances in predicting diagnosis of COVID-19 infection Time: BaselineDescription: NPV reflects the probability that the absence of olfactory and taste disturbances will have a negative diagnosis of COVID-19. This is derived from dividing the number of patients without olfactory & taste disturbances and without COVID-19 infection over the total number of patients with no olfactory and taste disturbances, and multiplying by 100%
Measure: Negative predictive value (NPV) of olfactory and taste disturbances in predicting absence of COVID-19 infection Time: BaselineDescription: The percentage of true positives, i.e. the proportion of patients with olfactory and taste disorders with COVID-19 infection. This can be calculated by dividing the number of subjects with olfactory & taste disturbances who have COVID-19 infection with the number of patients with olfactory & taste disturbances, and multiplying by 100%
Measure: Sensitivity of olfactory and taste disturbances in predicting COVID-19 infection Time: BaselineDescription: The percentage of true negatives, i.e. the proportion of patients without olfactory and taste disorders who do not have COVID-19 infection. This can be calculated by dividing the number of subjects without olfactory & taste disturbances who do not have COVID-19 infection with the number of patients without olfactory & taste disturbances, and multiplying by 100%
Measure: Specificity of olfactory and taste disturbances in predicting COVID-19 infection Time: BaselineWe will study genetic factors causing severe disease due to infection with SARS-COV-2 which may help to find targeted therapy
Description: Genetic susceptibility to COVID-19
Measure: Mutations leading to increase susceptibility to SARS-COV-2 infection Time: 12 monthsThe purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Organicell Flow for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.
Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician
Measure: Incidence of any infusion associated adverse events Time: 60 DaysDescription: Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Measure: Incidence of Severe Adverse Events Time: 60 DaysDescription: Measured at day 60 or at hospital discharge, whichever comes first.
Measure: All Cause Mortality Time: 60 DaysDescription: Number of participants that are alive at 60 days post first infusion follow up
Measure: Survival Rate Time: 60 DaysDescription: Measure IL-6, IL-2, TNF-alpha from serum of blood samples
Measure: Cytokine Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab
Measure: D-dimer Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: CRP from serum of blood samples
Measure: C-reactive protein Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: Viral load by real time RT methodology using blood samples or nose / throat swab
Measure: Quantification of the COVID-19 Time: Day 0, Day 4, Day 8Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.
Measure: Improved Organ Failure Time: Day 30Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.
Measure: Chest Imaging Changes Time: Day o, Day 30COVID-19 infection has spread worldwide causing several deaths in few months Convalescent Plasma from COVID 19 donors has shown huge activity in small series from Chinese patients and currently many centers from USA and the European Union are assessing its use looking to avoid mortality and prolonged hospitalizations COVID-19-related
Description: in-hospital mortality secondary to COVID-19 among patients treated with convalescent plasma
Measure: in-hospital mortality secondary to COVID-19 among patients treated with convalescent plasma Time: 1 yearDescription: safety of convalescent plasma from COVID 19 donors (CTCAE V5.0)
Measure: safety of the use of convalescent plasma drom COVID 19 donors Time: 1 yearDescription: any cause of mortality during these periods
Measure: Mortality at 30 days, 90 days, 6 months and 1 year Time: 1 yearDescription: based on results from this trial comparing with official information
Measure: in-hospital Mortality COVID-19 related compared with non-treated population according to Chilean official reports Time: through study completion, an average of 1 yearDescription: number of days of hospitalization in high complexity facilities after convalescent plasma use
Measure: Number of days of hospitalization in high complexity facilities after convalescent plasma use Time: 1 yearDescription: number of days of hospitalization in intensive care unit after convalescent plasma use
Measure: Number of days of hospitalization in intensive care unit after convalescent plasma use Time: 1 yearDescription: number of days of mechanical ventilatory support in patients after convalescent plasma use
Measure: Number of days of mechanical ventilatory support in patients after convalescent plasma use Time: 1 yearDescription: total number of days of mechanical ventilatory support
Measure: Total number of days of mechanical ventilatory support Time: 1 yearDescription: total number of hospitalization days in patients treated with convalescent plasma
Measure: Total number of hospitalization days in patients treated with convalescent plasma Time: 1 yearDescription: total number of hospitalization days in patients after treatment with convalescent plasma
Measure: Number of hospitalization days in patients after treatment with convalescent plasma Time: 1 yearDescription: Viral load measuring
Measure: Viral load measuring Time: 14 daysDescription: COVID19-Immunoglobulin M and Immunoglobulin G, neutralizing antibodies
Measure: Immunological response in treated patients (COVID19-Immunoglobulin M and Immunoglobulin G, neutralizing antibodies) Time: day 1 of hospitalizationDescription: negativization of COVID 19 load since convalescent plasma use
Measure: Negativization of COVID 19 load since convalescent plasma use Time: 14 daysDescription: negativization of COVID 19 load since hospitalization
Measure: Negativization of COVID 19 load since hospitalization Time: 14 daysDescription: negativization of COVID 19 load since first reported symptoms COVID-19 related
Measure: Negativization of COVID 19 load since first reported symptoms COVID-19 related Time: 14 daysDescription: Interferon Gamma measurement from donor
Measure: Donor Interferon Gamma profile characterization Time: 1 dayDescription: Granulocyte Macrophage Colony Stimulating Factor measurement from donor
Measure: Donor Granulocyte Macrophage Colony Stimulating Factor characterization Time: 1 dayDescription: Tumor Necrosis Factor Alfa measurement from donor
Measure: Donor Tumor Necrosis Factor Alfa characterization Time: 1 dayDescription: Interleukin -1 beta measurement from donor
Measure: Donor Interleukin -1 beta characterization Time: 1 dayDescription: Interleukin -2 measurement from donor
Measure: Donor Interleukin-2 characterization Time: 1 dayDescription: Interleukin -4 measurement from donor
Measure: Donor Interleukin-4 characterization Time: 1 dayDescription: Interleukin -6 measurement from donor
Measure: Donor Interleukin-6 characterization Time: 1 dayDescription: Interleukin -8 measurement from donor
Measure: Donor Interleukin-8 characterization Time: 1 dayDescription: Interleukin -10 measurement from donor
Measure: Donor Interleukin-10 characterization Time: 1 dayDescription: Interferon Gamma measurement from receptor
Measure: Receptor Interferon Gamma profile characterization Time: 1 dayDescription: Granulocyte Macrophage Colony Stimulating Factor measurement from receptor
Measure: Receptor Granulocyte Macrophage Colony Stimulating Factor characterization Time: 1 dayDescription: Tumor Necrosis Factor Alfa measurement from receptor
Measure: receptor Tumor Necrosis Factor Alfa characterization Time: 1 dayDescription: Interleukin -1 beta measurement from receptor
Measure: receptor Interleukin -1 beta characterization Time: 1 dayDescription: Interleukin -2 measurement from receptor
Measure: Receptor Interleukin-2 characterization Time: 1 dayDescription: Interleukin -4 measurement from receptor
Measure: Receptor Interleukin-4 characterization Time: 1 dayDescription: Interleukin -6 measurement from receptor
Measure: Receptor Interleukin-6 characterization Time: 1 dayDescription: Interleukin -8 measurement from receptor
Measure: Receptor Interleukin-8 characterization Time: 1 dayDescription: Interleukin -10 measurement from receptor
Measure: Receptor Interleukin-10 characterization Time: 1 dayPassive immunotherapy through plasma infusion of convalescent subjects - convalescent plasma - or "hyperimmune" plasma was one of the most widespread and effective anti-infective treatments in the pre-antibiotic era and one of the founding pillars of immunology, and has also been used during the SARS (2002-2003) and Ebola (2014-2016) viral epidemy for which there were no alternative immunoprophylactic or therapeutic interventions. To date, there are not proven etiological therapies for SARS-CoV-2 infection, the agent responsible for the disease called Covid-19. Among those subjected to clinical studies during the current epidemic in China, hyperimmune plasma appears to be one of the most rational and promising. The objective of this study will be to evaluate the efficacy and safety of the hyperimmune plasma administered add-on to the anti-Covid-19 treatment (standard therapy) according to clinical practice in patients with severe Covid-19 infection, compared to patients with severe Covid-19 infection treated only with standard therapy.
Description: Statistically significant reduction (P <0.05) of mortality in the group of patients treated with hyperimmune plasma vs patients treated with standard therapy.
Measure: decrease in mortality Time: 30 daysDescription: Statistically significant increase (P <0.05) of lymphocyte levels after 7 and 14 days after the start of treatment with hyperimmune plasma (treated group), compared to the control group.
Measure: lymphocytes Time: 7 and 14 daysDescription: Statistically significant reduction (P <0.05) of plasma levels of reactive protein C (expressed as mg/L), 7 and 14 days after the start of treatment with hyperimmune plasma vs standard therapy (group control)
Measure: PCR levels vs control Time: 7 and 14 daysDescription: Statistically significant reduction (P <0.05) of plasma levels of reactive protein C (expressed as mg/L), 7 and 14 days after the start of treatment with hyperimmune plasma vs the same patients before the beginning of the treatment
Measure: PCR levels vs before treatment Time: 7 and 14 daysDescription: Significant Correlation (P<0.05) between hyperimmune plasma antibody levels and clinical improvement time (expressed in days)
Measure: AB levels and clinical improvement Time: 30 daysDescription: Statistically significant reduction (P <0.05) of plasma levels of IL-6 (expressed as pg/mL) and TNF-alpha (expressed as pg/mL), 7 and 14 days after the start of treatment with hyperimmune plasma vs standard therapy (group control)
Measure: Inflammatory cytokines vs controls Time: 7 and 14 daysDescription: Statistically significant reduction (P <0.05) of plasma levels of IL-6 (expressed as pg/mL) and TNF-alpha (expressed as pg/mL), 7 and 14 days after the start of treatment with hyperimmune plasma vs the same patients before the beginning of the treatment
Measure: Inflammatory cytokines vs before treatment Time: 7 and 14 daysSNG001 is an inhaled drug that contains a antiviral protein called interferon beta (IFN-β). IFN-β in produced in the lungs during viral lung infections. It has been shown that older people and people with some chronic diseases have an IFN-β deficiency. Many viruses inhibit IFN-β as part of their strategy to evade the immune system. Addition of IFN-β in vitro protects lung cells from viral infection. IFN-β protects cells against the MERS and SARS coronaviruses (close relatives of SARS-CoV-2, the virus that causes COVID-19). SNG001 is an inhaled formulation of interferon beta-1a it is currently in Phase II clinical trials for COPD patients. Synairgen has conducted randomised placebo controlled clinical trials of SNG001 involving >200 asthma and COPD patients. These trials have shown that SNG001 has: - been well tolerated during virus infections - enhanced antiviral activity in the lungs (measured in sputum and blood samples) - provided significant lung function benefit over placebo in asthma in two Phase II trials. Synairgen believes SNG001 could help prevent worsening or accelerate recovery of severe lower respiratory tract illness in COVID-19 patients. Patients who are in hospital or non-hospitalised but are a high risk groups (e.g. elderly or diabetics) will be invited to take part in the trial. The patient would receive either SNG001 or placebo once daily for 14 days. The severity of the patients condition would be recorded on a scale developed by the World Health Organisation and the patient would be asked questions about their breathlessness, cough and sputum every day, as well as assess their general medical condition and safety. If SNG001 proves to be beneficial it would be a major breakthrough for the treatment of COVID-19.
Description: Change in condition measured using the Ordinal Scale for Clinical Improvement during the dosing period - minimum of 0 (patient is well) to a maximum of 8 (death)
Measure: Ordinal Scale for Clinical Improvement Time: Day 1 to day 28Description: Progression to pneumonia as diagnosed by chest x-ray, if no pneumonia is present at time of enrolment
Measure: Progression to pneumonia Time: Day 2 to day 28Description: Evolution of pneumonia, as diagnosed by chest x-ray, if pneumonia is present at time of enrolment
Measure: Progression to pneumonia Time: Day 1 to day 28Description: Time to clinical improvement
Measure: Time to clinical improvement Time: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hoursDescription: NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response)
Measure: National Early Warning Score 2 (NEWS2) assessment of acute-illness severity Time: Day 1 to day 28Description: Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms)
Measure: Changes in daily breathlessness, cough and sputum scale (BCSS) Time: Day 1 to day 28Description: Looking at blood pressure measured in mmHg
Measure: Safety and tolerability - blood pressure II. Viral load Time: Day 1 to day 28Description: Looking at heart rate measured in beats per minute
Measure: Safety and tolerability - heart rate II. Viral load Time: Day 1 to day 28Description: Looking at temperature measured in degrees Celsius
Measure: Safety and tolerability - temperature II. Viral load Time: Day 1 to day 28Description: Looking at respiratory rate measure in breaths per minute
Measure: Safety and tolerability - respiratory rate II. Viral load Time: Day 1 to day 28Description: Looking at oxygen levels measured in a %
Measure: Safety and tolerability - oxygen saturation II. Viral load Time: Day 1 to day 28Description: Looking at adverse events (numbers and terms)
Measure: Safety and tolerability - adverse events II. Viral load Time: Day 1 to day 28Description: Looking at concomitant medications given during treatment
Measure: Safety and tolerability - concomitant medications II. Viral load Time: Day 1 to day 28In December 2019, the first patients infected with the 2019 novel coronavirus (2019-nCoV) were diagnosed in Wuhan. The clinical presentation and course of Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2) infection is poorly understood in older patients and is certainly different from the general population. This project is designed to better understand and to determine clinical, biological and radiological markers of poor adverse outcomes in hospitalized older patients diagnosed with COVID-19.
Description: We measure functional score of comorbidities
Measure: To evaluate the relative contributions of comorbidities on intra-hospitalized death Time: 1 monthDescription: We measure Functional Independence Measure scale
Measure: To evaluate the relative contributions of functional characteristics on intra-hospitalized death Time: 1 monthDescription: We describe the role fo geriatric syndrome such as delirium, falls
Measure: To explore specific clinical profiles that may influence COVID-19 disease outcomes in the elderly based on geriatrics syndromes Time: 1 monthSarilumab is an anti-interleukin-6 human monoclonal antibody, such as tocilizumab, which is administered subcutaneously every two weeks for the treatment of moderate to severe active rheumatoid arthritis in adult patients. Despite the effectiveness reported for tocilizumab in the recently published experiences, the need to rapidly find alternative therapies to manage the complications of Covid-19 infection remains extremely high. The lack of clinical experience on the usage of sarilumab in such patients prevents the possibility of adopting early access programs for using commercially available sarilumab (prefilled syringe) packs in patients with severe Covid-19 pneumonia. The present study is aimed to generate a rapid, still robustly documented, evidence on the potential clinical efficacy and tolerability of a further IL-6R antagonist in Covid-19 pneumonia.
Description: Clinical efficacy of sarilumab in adult patients hospitalized due to severe Covid-19 pneumonia based on the proportion of patients who show an improvement of the respiratory function, described as ≥30% decrease in oxygen requirement compared to baseline (as defined as the ratio of O2 flow through the Venturi mask).
Measure: Proportion of patients who show an improvement of the respiratory function Time: 6 weeksDescription: Evaluation of the time to resolution of fever, defined as body temperature ≤36.6°C axilla, ≤37.8°C rectal or tympanic for at least 48 hours without antipyretics in patients with fever at baseline.
Measure: Evaluation of the time to resolution of fever Time: 6 weeksDescription: Evaluation of the viral load on blood and sputum for COVID-19
Measure: Evaluation of the viral load on blood and sputum for COVID-19 Time: Before administration of sarilumab, 48 hours and 96 hours after administrationDescription: Evaluation of the plasma concentration of GM-CSF
Measure: Evaluation of the plasma concentration of GM-CSF Time: Pre-treatment and 96 and 120 hours post-treatmentDescription: Evaluation of the plasma concentration of Il-6
Measure: Evaluation of the plasma concentration of Il-6 Time: Pre-treatment and 96 and 120 hours post-treatmentDescription: Evaluation of the plasma concentration of TNF-α
Measure: Evaluation of the plasma concentration of TNF-α Time: Pre-treatment and 96 and 120 hours post-treatmentDescription: Evaluation of the rate of progression of WBC fraction of immature granulocytes - IG - (absolute count).
Measure: Evaluation of the rate of progression of White Blood Cell (WBC) fraction Time: 96 and 120 hours post-treatmentIntroduction: The SARS-Cov-2 outbreak in France and the concomitant massive increase in the number of cases requiring hospital management create a major risk of COVID-19 infection for hospital staff. In addition to nosocomial transmission, the health care workers (HCWs), defined as persons serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials, are also exposed to community transmission. Whether HCWs acquire infection at work or in the community is important to adapt protection measures. A few studies investigated COVID-19 infection among medical and nursing personnel. However, none have analyzed all categories of hospital staff. As of April 9, 2020, a total of 9,282 US HCWs with confirmed COVID-19 had been reported to CDC (US), however description of occupational activities was not available. Therefore, limited information is available about COVID-19 infection among HCWs. Thus, the objectives of the sdudy are to estimate the incidence of symptomatic SARS-CoV-2 infection in HCWs in five university hospitals (including geriatric hospitals) of the great Paris area and to estimate both nosocomial and community risk factors. Method: A prospective and retrospective cohort study that includes all hospital staff (including medical and nursing personnel, health care managers, laboratory, radiology, reception staffs, stretcher-bearers, etc.) working in different departments of five university hospitals (acute medical centers and geriatric hospitals) in the great Paris area (9 000 HCWs). Incidence of symptomatic SARS-CoV-2 infection will be estimated with its 95%CI. Individual and contextual risk factors will be analyzed using multilevel multivariate logistic regression modelling to account for clustering and confounding. Conclusion This study should make it possible to better characterize SARS-Cov-2 contamination of HCWs and to estimate the share of nosocomial transmission.
Description: The primary endpoint will be the occurrence of confirmed (RT-PCR or work stopping) SARS-CoV-2 infection.
Measure: SARS-COV-2 infection Time: At inclusionDescription: The primary endpoint will be the occurrence of confirmed (RT-PCR or work stopping) SARS-CoV-2 infection.
Measure: SARS-COV-2 infection Time: Up to 3 monthsDescription: Individual factors collected by a self-questionnaire
Measure: Individual factors Time: At inclusionDescription: Individual factors collected by a self-questionnaire
Measure: Individual factors Time: Up to 3 monthsDescription: Weekly consumption of masks and hydroalcoholic solution
Measure: Hospital ward level Time: Up to 3 monthsIn December 2019, an outbreak of pneumonia associated with a novel coronavirus named as severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) was reported in Wuhan city, China, and spread exponentially throughout China and other countries in the following weeks. It is recommended that elective endoscopies should be deferred during the COVID-19 outbreak for the potential transmission between patients and medical staff in the statements of Asian Pacific Society for Digestive Endoscopy (APSDE-COVID statements). Therefore, exploring an alternative for patients with the requirements of endoscopy during the outbreak is of great importance. Herein,the investigators developed an novel non-contact magnetically-controlled capsule endoscopy (Nc-MCE) system (Figure 1) adds a remote control workstation and a audio-visual exchange system to the original well-established MCE system. This study was a open-label, prospective, randomized controlled study approved by the institutional review board of Shanghai Changhai Hospital. It was designed to evaluate the diagnostic utility, safety, feasibility and patients acceptability of Nc-MCE in patients with an indication of endoscopy, and comparing it with the result of MCE.
Description: Maneuverability score was the sum of four subjective scores rated by the operator (signal transmission quality score, operating comfort score, gastric visualization score and study subject compliance score), each of which ranged from 1 to 5 denoting the lowest to the highest degree of satisfaction.
Measure: Maneuverability score Time: During the procedureDescription: GET was defined as the time time taken for the endoscopist to complete the gastric examination to his or her satisfaction
Measure: Gastric examination time(GET) Time: During the procedureDescription: The investigators use a satisfaction questionnaire to evaluate the comfort and acceptability of each patient
Measure: the comfort and acceptability of patients Time: After the procedure(within 5 days)Description: Diagnosis based on the data of nc- MCE by two endoscopist
Measure: diagnostic yield Time: after the procedure(within 5 days)Description: Adverse events during and after the procedure
Measure: Adverse events Time: During and within 2 weeks after the procedureDescription: Complete observation of the mucosa (>90% of the mucosa observed) in gastric cardia, fundus, body, angulus, antrum and pylorus
Measure: Clinical success Time: During the procedureThe PROTECT open-label randomised basket trial will assess the effectiveness of hydroxychloroquine (HCQ) as chemoprophylaxis against COVID-19 in multiple vulnerable populations in the United Kingdom.
Description: The primary outcome for PROTECT is the time to confirmed COVID-19 infection from the date of randomisation. This will be captured via linkage with PHE or by direct reporting by sites.
Measure: Time to confirmed diagnosis of COVID-19 Time: To study completion, average 6 monthsDescription: Death from any cause
Measure: All-cause mortality Time: To study completion, average 6 monthsDescription: Severity will be assessed by requirement for hospitalisation, HDU/ICU admission or death and Length of inpatient stay.
Measure: Severity of COVID-19 disease Time: To study completion, average 6 monthsDescription: Acute respiratory distress syndrome, viral pneumonitis, myocarditis/myocardial injury, acute kidney injury.
Measure: Incidence of COVID-19 complications Time: To study completion, average 6 monthsTo evaluate the efficacy of using Desferal injections for prevention of ARDS in moderate cases with fever , chest tightness and relevant chest images
Description: patient dies from ARDS
Measure: Mortality rate Time: two weeksDescription: time to recovery
Measure: Duration of severe symptoms Time: two weeksThis project investigates individual treatments using convalescent severe acute respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plasma in SARS-CoV-2 infected patients at risk for disease progression. In addition to standard of care, SARS-CoV-2 infected patients for whom blood group compatible convalescent plasma is available and who are willing to sign the informed consent receive convalescent plasma. Only patients with moderate to severe disease at risk for transfer to intensive care unit or patients at the intensive care unit with limited treatment options will be treated.
Description: Serious adverse events during the study period include transfusion reaction (fever, rash), transfusion related acute lung injury (TRAU) , transfusion associated circulatory overload (TACO) , transfusion related infection
Measure: Serious adverse events in convalescent plasma treated patients Time: From baseline (enrolment) to 24 hours follow-upDescription: Change in SARS-CoV2 quantitative in nasopharyngeal swab
Measure: Virologic clearance in nasopharyngeal swab of convalescent plasma treated patients Time: at Baseline (admission to Covid-ward), day -1 (before plasma), day 1 (after plasma), day7, day 14, day 28Description: Transfer to ICU
Measure: Transfer to ICU Time: at Baseline (admission to Covid-ward) until day 28Description: in-hospital death
Measure: in-hospital death Time: at Baseline (admission to Covid-ward) until day 28Description: Change in SARS-CoV2 quantitative in plasma
Measure: Virologic clearance in plasma of convalescent plasma treated patients Time: at Baseline (admission to Covid-ward), day -1 (before plasma), day 1 (after plasma), day7, day 14, day 28Description: Duration of hospitalisation
Measure: Time to discharge from hospital after enrolment Time: at Baseline (admission to Covid-ward) until discharge (approx. 28 days)Description: Rise of SARS-CoV-2 antibody titers (on day 1, 7, 14 and 28)
Measure: Humoral immune response Time: at Baseline (admission to Covid-ward), day -1 (before plasma), day 1 (after plasma), day7, day 14, day 28SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra.
Description: Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment
Measure: Proportion of patients with a positive SARS-CoV-2 PCR Time: 7 days post-treatmentDescription: Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab
Measure: Mean viral load Time: Baseline and on days 4, 7, 14 and 21Description: Proportion of patients with fever and cough at days 4, 7, 14 and 21 as well as proportion of patients progressing to severe disease or death during the trial
Measure: Fever and cough progression Time: Up to and including day 21Description: Proportion of participants with positive IgG at day 21
Measure: Seroconversion at day 21 Time: Up to and including day 21Description: Proportion of drug-related adverse events
Measure: Proportion of drug-related adverse events Time: 7 days post treatmentDescription: Levels in median fluorescence intensity (MFI) of IgG, IgM and IgA against the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 in plasma, measured by a Luminex assay
Measure: Levels of IgG, IgM and IgA Time: Up to and including day 28Description: Frequency (% over total PBMC) of innate immune cells (myeloid and plasmacytoid dendritic cells, NK cell, classical, intermediate and pro-inflammatory macrophages) measured in cryopreserved PBMC by flow cytometry
Measure: Frequency of innate immune cells Time: Up to and including day 7Description: Frequency of CD4+ T and CD8+ T cells (% over total CD4+T and CD8+ T) expressing any functional marker upon in vitro stimulation of PBMC with SARS-CoV-2 peptides, measured by flow cytometry
Measure: Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T cells Time: Up to and including day 7Description: Concentration (all in pg/mL) of epidermal growth factor (EGF), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1RA, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p40/p70), IL-13, IL-15, IL-17, IFN-γ induced protein (IP-10), monocyte chemoattractant protein (MCP-1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1β in plasma measured by a Luminex assay using a commercially available kit (Cytokine Human Magnetic 30-Plex Panel from ThermoFisher)
Measure: Results from cytokine Human Magnetic 30-Plex Panel Time: Up to and including day 28The Malaysian COVID-19 Anosmia Study is a nationwide multicentre observational study to investigate the prevalence and characteristics of olfactory and gustatory/taste disturbances in COVID-19 infection in Malaysia, and to evaluate the predictive value of screening for these symptoms in COVID-19 infection. This study consists of two phases: the first phase is a cross-sectional study and the second phase is a case-control study. The cross-sectional study is described here (the case-control study is described in a separate ClinicalTrials.gov record).
Description: In the patient-reported online questionnaire, subjects will be asked regarding whether they experienced symptoms of olfactory and/or taste disturbances
Measure: Presence or absence of olfactory and taste disturbances in COVID-19 patients Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: Percentage of COVID-19 patients experiencing olfactory disturbances (anosmia or hyposmia)
Measure: Prevalence of olfactory disturbances in COVID-19 patients Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: Percentage of COVID-19 patients experiencing taste disturbances
Measure: Prevalence of taste disturbances in COVID-19 patients Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked regarding other symptoms they experienced when they were diagnosed with COVID-19 (e.g. headache, nasal congestion, fever, chills, cough, dyspnoea, gastrointestinal symptoms, eye & ear symptoms)
Measure: Clinical manifestations of study participants Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked regarding their pre-existing health conditions (for example, obesity, diabetes, hypertension, cardiac conditions, previous head trauma, chronic rhinosinusitis, etc.)
Measure: Other pre-existing health conditions Time: Prior to diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked to rate their sense of smell and taste before their diagnosis of COVID-19 infection
Measure: Rating of baseline sense of smell & taste in COVID-19 patients prior to diagnosis of their infection Time: Prior to 2 weeks preceding the diagnosis of COVID-19 infection (Baseline)Description: In the patient-reported online questionnaire, subjects will be asked to rate their sense of smell and taste at the time of diagnosis of COVID-19 infection
Measure: Rating of sense of smell & taste in COVID-19 patients at time of diagnosis of their infection Time: Within 2 weeks preceding the diagnosis of COVID-19 infectionDescription: In the patient-reported online questionnaire, subjects will be asked to rate their sense of smell and taste at the time of answering questionnaire survey
Measure: Rating of sense of smell & taste in COVID-19 patients at time of answering questionnaire survey Time: Up to 6 monthsA prospective case-control pilot study to evaluate the possible effect of a probiotic mixture in the improvement of symptoms, the reduction in the number of days of hospitalization and the increase in the percentage of patients with negative PCR after infection with the coronavirus SARS-CoV-2.
Description: Percentage of patients with discharge to ICU.
Measure: Cases with discharge to ICU. Time: 30-daysDescription: Percentage of patients with home discharge.
Measure: Patients with home discharge. Time: 30-daysDescription: Percentage of deaths.
Measure: Mortality. Time: 30-daysDescription: Number of adverse events that occur during the treatment period, attributable or not to the intervention product.
Measure: Treatment safety assessed by number of adverse events. Time: 30-daysDescription: Number of new cases of positive SARS-Cov-2 infection by PCR analysis.
Measure: New cases of SARS-Cov-2 infection among healthcare personnel caring for the patients. Time: 30-daysDescription: Percentage of patients with negative PCR for SARS-CoV-2.
Measure: Patients with negative PCR result for SARS-CoV-2 infection. Time: 30-daysBackground: In December 2019, patients with pneumonia secondary to a new subtype of Coronavirus (COVID-19) were identified in China. In a few weeks the virus spread and cases started practically all over the world. In February 2020, the WHO declared a pandemic. Severe symptoms have been found in patients mainly with comorbidities and over 50 years of age. At this time there is no proven therapeutic alternative. In vitro studies and observational experiences showed that antimalarial drugs (Chloroquine and hydroxychloroquine) had antiviral activity and increased viral clearance. Ivermectin, on the other hand, has been shown in vitro to reduce viral replication and in an observational cohort, greater viral clearance with promising clinical results. So far there is no standard of treatment and clinical trials are needed to find effective treatment alternatives. Objective: To evaluate the safety and efficacy of treatment with hydroxychloroquine and ivermectin for serious COVID-19 infections in no critical hospitalized patients. Material and methods: Randomized controlled trial of patients diagnosed with respiratory infection by COVID-19, who present criteria for hospitalization. Randomization will be performed to receive hydroxychloroquine at a dose of 400 mg every 12 hours for one day and then 200 mg every 12 hours, to complete a 5-day treatment schedule. Group 2: Ivermectin 12 mg every 24 hours for one day (less than 80 kg) or Ivermectin 18 mg every 24 hours for one day (greater than 80 kg) + placebo until the fifth day. Group 3: Placebo. Prior to randomization, the risk of cardiovascular complications determined by corrected QT interval, related to hydroxychloroquine intake will be assessed. If the patient is at high risk, the allocation will be to ivermectin only or to placebo in an independent randomization, if the risk is low, any of the three groups could be assigned. Outcomes: The primary outcome will be discharge from hospital for improvement. The safety outcomes will be requirement of mechanical intubation, septic shock or death. Viral clearance will also be evaluated by means of PCR, which will be taken on the 5th day after admission, day 14 and 21.
Description: Days from admission as a suspected case of COVID with hospitalization criteria until discharge
Measure: Mean days of hospital stay Time: Three monthsDescription: Respiratory deterioration defined by respiratory rate > 25 per minute, requirement of high oxygen supply (FiO2 > 80% ) to maintain oxygen saturation > 90 %, invasive mechanical ventilation or dead.
Measure: Rate of Respiratory deterioration, requirement of invasive mechanical ventilation or dead Time: Three monthsDescription: Daily delta of oxygenation index during the hospitalization
Measure: Mean of oxygenation index delta Time: Three monthsDescription: Mean time to viral negativization of RT-qPCR SARS-CoV-2. Pre Specified time: 5, 14, 21 and 28 days after the first positive PCR.
Measure: Mean time to viral PCR negativization Time: One monthThe most severe manifestations of COVID-19 include respiratory failure, coagulation problems, and death. Inflammation and blood clotting are believed to play an important role in these manifestations. Research in humans has shown that dipyridamole can reduce blood clotting. This research study is being conducted to learn whether 14 days of treatment with dipyridamole will reduce excessive blood clotting in COVID-19. This study will enroll participants with confirmed coronavirus (SARS-CoV)-2 infection that are admitted to University of Michigan. Eligible participants will be randomized to receive dipyridamole or placebo for 14 days in the hospital. In addition, data will be collected from the medical record, and there will also be blood draws during the hospitalization.
Description: Increase in plasma D-dimer level compared with baseline at enrollment.
Measure: Change in D-dimer Time: baseline, up to approximately 28 days after last study drug administrationDescription: Global composite rank score of death, mechanical ventilation, oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2), and World Health Organization (WHO) Ordinal score.
Measure: Global composite rank score Time: up to approximately 28 days after last study drug administrationInvivoscribe, Inc. and its wholly owned subsidiary LabPMM, LLC are collecting peripheral blood specimens from patients with suspected SARS-CoV-2 viral infections. These donors will be from a population of patients who are already providing nasal pharyngeal (NP) swab samples in universal transport media (UTM) for COVID-19 testing at LabPMM LLC. Specimens meeting this research protocol's inclusion criteria may be evaluated with various molecular techniques in order to identify nucleic acid sequences, antibodies, and/or antigens with the potential of being used to develop novel SARS-CoV-2 detection methods and COVID- 19 treatments and/or prevention methods (e.g. drug or vaccine development).
Description: This research protocol describes the collection and analysis of peripheral blood samples to: Identify nucleic acid sequences that may be used aide in the development of SARSCoV- 2 detection methods. Identify antibodies that may be used aide in the development of SARS-CoV-2 detection methods. Identify antigens that may be used aide in the development of SARS-CoV-2 detection methods. Identify nucleic acid sequences that may be used aide in the development of COVID- 19 treatments and/or vaccines. Identify antibodies that may be used aide in the development of COVID-19 treatments and/or vaccines. Identify antigens that may be used aide in the development of COVID-19 treatments and/or vaccines.
Measure: Identification of nucleic acid sequencing, antibodies and antigens to be used in detection methods or treatments and/or vaccines Time: 2 yearsPurpose of Study • The purpose of this study to evaluate, the effectiveness of convalescent plasma in combatting the symptoms and effects of the coronavirus disease, COVID-19. Beyond supportive care, there are no proven treatment options for COVID-19.
Description: % patients who survived
Measure: Survival Rate Time: At 28 DaysIt might be necessary with Sars-Cov2 pneumopathy patient to repeat thoracic images, the tomodensitometry ones in particular. This task is difficult and nearly impossible for several reasons: respiratory and hemodynamic unstable patient, prone position and due to the high contagious nature of the disease. The lung ultrasound is an easy tool, fast (between 5 and 10 minutes) and as a limited training. In the context of the Sars-Cov2 epidemic, Buonsenso and al case report depict the first lung ultrasound for a Covid 19 patient. Peng and al in Intensive Care Medicine accentuate the usefulness of this particular technic. In the American Journal of Respiratory and Critical Care Medicine, a study has been published as a point-of-care, in which the doctors reported using the lung ultrasound with intensive and critical care patient. In Critical Care 2016, it has been showed that ultrasound allowed with neat precisions, to predict severe ARDS patient response to the prone position, all-cause. Another researchers team found a good correlation between lung ultrasound, the SOFA, APACHE II, CPIS score, and patient mortality. And a new applicability in the pulmonary recruitment by PEEP titration has been presented. The aim of this study is to evaluate the lung ultrasound in Covid19 ARDS.
Description: In dorsal position, or in prone position, the two hemithorax will be subdivided in 6 parts, and a score will be attributed with the following criteria : A-Lines (0 point), > 3 B-lines (1 point), B-Lines coalscent (2 points), and pulmonary consolidation (3 points). For the echography we can use a convexe sonde, or a "cardiac" sonde.
Measure: LUS applicability with COVID 19 Time: 10 monthsDescription: Comparison between Xray / CT scan exam and LUS
Measure: Radiographic correlation (chest Xray and tomodensitometry) Time: 10 monthsDescription: according to LUS score, ventilatory mode and parameters, medical history and bood analysis results
Measure: LUS Mortality prediction Time: 10 monthsDescription: comparison of LUS score depending of the position used for performing LUS
Measure: Prediction of Prone position response Time: 10 monthsThis is a Phase I open-label interventional study which will test the efficacy of ResCure™ in the treatment of patients with COVID-19 infection.
Description: Number of days from COVID-19 diagnosis to recovery via RT-PCR
Measure: The rate of recovery of mild or moderate COVID-19 in patients using ResCure™ Time: 12 WeeksDescription: Reduction and/or progression of symptomatic days, reduction of symptom severity
Measure: Reduction or progression of symptomatic days Time: 12 WeeksDescription: Pulse from baseline to 12 weeks
Measure: Assess the safety of ResCure™ via pulse Time: 12 WeeksDescription: Oxygen saturation from baseline to 12 weeks
Measure: Assess the safety of ResCure™ via oxygen saturation Time: 12 WeeksDescription: EKG from baseline to 12 weeks
Measure: Assess the safety of ResCure™ via EKG Time: 12 WeeksDescription: Assess Adverse Events and Serious Adverse Events due to ResCure™
Measure: Assess Tolerability of ResCure™ Time: 12 WeeksThis is a phase 1b randomized, double-blind, placebo-controlled study in adult subjects with Coronavirus Disease 2019 (COVID-19). This clinical trial will evaluate the preliminary safety and efficacy of BM-Allo.MSC vs placebo in treating subjects with severe disease requiring ventilator support during COVID 19 infection.
Description: Incidence of AEs within 30 days of randomization.
Measure: Incidence of AEs Time: 30 daysDescription: Mortality within 30 days of randomization.
Measure: Mortality Time: 30 daysDescription: Cause of death within 30 days of randomization
Measure: Death Time: 30 daysDescription: Number of ventilator-free days within 60 days of randomization.
Measure: Number of ventilator-free days Time: 60 daysDescription: Time from randomization to an improvement of one category using the ordinal scale. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities
Measure: Improvement of one category Time: 30 daysDescription: Change in the 7-point ordinal scale from baseline. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities
Measure: 7-point ordinal scale Time: 30 daysDescription: Change in NEWS from baseline. The following 7 clinical parameters will be assessed: Respiration rate Oxygen saturation Any supplemental oxygen Temperature Systolic blood pressure Heart rate Level of consciousness Measurements within normal ranges are assigned a 0. If the measurement in each category is substantially above or below the normal range, it is given a +1, +2, or +3. The more far off than normal, the bigger the number (in each category). A higher number indicates worse outcome. Each category can be 0-3, except for supplemental oxygen which is only 0-2. The highest value a patient can get is 20.
Measure: NEWS Time: 30 daysDescription: Time from randomization to discharge or to a NEWS of ≤ 2 maintained for 24 hours, whichever occurs first.
Measure: NEWS of ≤ 2 Time: 30 daysDescription: Change from baseline in Sequential Organ Failure Assessment (SOFA) score on days 8, 15, 22, and 29. System Score for each category is 0-4 with 28 is the maximum score for worst outcome. The following categories are: Respiration Coagulation Liver Cardiovascular Central Nervous System Renal
Measure: Sequential Organ Failure Assessment (SOFA) Time: days 8, 15, 22, and 29Description: Number of days requiring oxygen.
Measure: Oxygen Time: 30 daysDescription: Duration of hospitalization from randomization.
Measure: Hospitalization Time: 30 daysDescription: Incidence of SAEs within 30 days of randomization
Measure: Incidence of SAEs Time: 30 daysThe COVID-19 pandemic is a global emergency threatening to take millions of lives in the United States and around the world. There is no current vaccine strategy against COVID-19 infection caused by a novel coronavirus named SARS-CoV-2. Studies with a related coronavirus called SARS-CoV-1 that caused the SARS outbreak in 2003 indicated that memory CD8+ T cells recognizing viral epitopes persisted for more than 6 years post infection while neutralizing antibodies and memory B cells were short-lived and were undetectable after a short period of time (Tang et al., 2011; Peng et al., 2006; Channappanavar et al., 2014). Thus, including viral epitopes that are recognized by memory CD8+ T cells is imperative for vaccines that can provide long-term immunity against SARS-CoV-2. In this study, blood samples from COVID-19 patients who have recovered from the infection will be used to identify the viral epitopes recognized by their memory CD8+ T cells. This will be accomplished using a genome-wide, high-throughput screening technology developed at Harvard Medical School (Kula et al., 2019) and licensed by the study sponsor, TScan Therapeutics. A 24,000-member library that tiles across all ~100 viral isolates of SARS-CoV-2 that have been sequenced so far has already been synthesized at TScan. Blood samples from convalescent patients are urgently needed to identify T cell receptors and immunogenic viral epitopes on SARS-CoV-2. It is the hope that these data will inform development of a vaccine with the potential for long-lasting protection against SARS-CoV-2.
Recent information appearing from different countries suggest that treatment of Coronavirus disease 2019 (COVID-19) with hydroxychloroquine or with a combination of hydroxychloroquine and azithromycin has either an indifferent effect on viral replication or substantial cardiotoxicity. This is a clinical trial aiming to prove that addition of oral clarithromycin to treatment regimen of COVID-19 is associated with early clinical improvement and attenuation of the high inflammatory burden of the host. The study will not comprise a placebo-comparator group since this is considered inappropriate in an era of a pandemic with substantial global mortality.
Description: This is defined on day 8 (End of Treatment - EOT). Patients with upper respiratory tract infection by SARS-CoV-2 meet the study primary endpoint if they were not admitted to hospital or their symptoms did not progress to lower respiratory tract infection. Patients who develop by day 8 severe respiratory failure do not meet the study primary endpoint.
Measure: Clinical outcome negative for two parameters(hospital admission/disease progression) Time: Day 1 to Day 8Description: This is defined on day 8 (EOT visit). Patients with lower respiratory tract infection by SARS-CoV-2 meet the primary endpoint if they present at least 50% decrease of the score of respiratory symptoms from the baseline. This score is the sum of scoring for the symptoms of cough, dyspnea, purulent sputum expectoration and pleuritic chest pain. Patients who develop by day 8 severe respiratory failure do not meet the study primary endpoint. Score ranges from 0 (no symptoms) to 9 (worst for all symptoms).
Measure: At least 50% decrease of the score of respiratory symptoms from the baseline Time: Day 1 to Day 8Description: Evaluation of need of hospitalization, SARS-CoV-2 infection progression from upper to lower respiratory tract infection, between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of two parameters with historical comparators from Hellenic Sepsis Study Group Database Time: Day 1 to Day 8Description: Respiratory score evaluation as described above between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database
Measure: Comparison of the score of respiratory symptoms with historical comparators from Hellenic Sepsis Study Group Database Time: Day 1 to Day 8Description: Comparison of clinical data (need of hospitalization, the infection progression of SARS-CoV-2 from upper to lower respiratory tract infections) in enrolled patients between baseline and study visit day 4 Patients who develop by day 4 severe respiratory failure do not meet the study secondary endpoint.
Measure: Clinical outcome negative for two parameters(hospital admission/disease progression) on day 4 Time: Day 4Description: This is defined on day 4 (5th visit). Patients with lower respiratory tract infection by SARS-CoV-2 meet the secondary endpoint if they present at least 50% decrease of the score of respiratory symptoms from the baseline. This score is the sum of scoring for the symptoms of cough, dyspnea, purulent sputum expectoration and pleuritic chest pain. Patients who develop by day 4 severe respiratory failure do not meet the study secondary endpoint. Score ranges from 0 (no symptoms) to 9 (worst for all symptoms).
Measure: At least 50% decrease of the score of respiratory symptoms from the baseline on day 4 Time: Day 4Description: Evaluation of range of enrolled patients who develop severe respiratory failure between baseline and day 14 (TOC VISIT). Severe respiratory failure is defined by presence of all of the following pO2/FiO2 less than 150 Need for mechanical or non-mechanical ventilation (CPAP)
Measure: Range of development of severe respiratory failure Time: Day 1 to Day 14Description: Evalution of hospital readmission until day 14 (TOC VISIT) from enrollement defined as either need of re-hospitalization for discharged patients or any need for hospitalization of out-patients.
Measure: Range of hospital readmission until day 14 Time: Day 1 to Day 14Description: Comparison of Real Time - Polymerase Chain Reaction (RT-PCR) results for SARS-CoV-2 viral load in rhinopharyngeal samples of enrolled patients at days 1, 4 and 8
Measure: Change of viral load in respiratory secretions from baseline on day 8 Time: Day 1 to Day 8Description: Change of cytokine production of monocytes in enrolled patients with upper/lower respiratory tract infection at days 1 and 8 (EOT) visit; monocytes will be stimulated for 24 hours with SARS-CoV-2 purified antigens for the production of TNFα. This will be analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of function of monocytes at days 1 and 8 Time: Day 1 to Day 8Description: Change of cytokine production of Th1 cells in enrolled patients with upper/lower respiratory tract infection at days 1 and 8 (EOT) visit; Th1 cells will be stimulated for 24 hours with SARS-CoV-2 purified antigens for the production of IFNγ. This will be analyzed separately for patients with upper and with lower respiratory tract infection.
Measure: Change of function of Th1 cells at days 1 and 8 Time: Day 1 to Day 8Description: Change of cytokine production of Th2 cells in enrolled patients with lower respiratory tract infection at days 1 and 8 (EOT) visit; Th2 cells will be stimulated for 24 hours with SARS-CoV-2 purified antigens for the production of IL6. This will be analyzed separately for patients with upper and with lower respiratory tract infection.
Measure: Change of function of Th2 cells at days 1 and 8 Time: Day 1 to Day 8Description: Change of the serum levels of interleukin-6 (IL-6) of enrolled patients between day 1 and day 8 (EOT VISIT); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of serum interleukin-6 (IL-6) cytokine levels between days 1 and 8 Time: Day 1 to day 8Description: Change of the serum levels of interleukin-8 (IL-8) of enrolled patients between day 1 and day 8 (EOT VISIT); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of serum interleukin-8 (IL-8) cytokine levels between days 1 and 8 Time: Day 1 to day 8Description: Change of the serum levels of human beta defensin-2 (hBD-2) of enrolled patients between day 1 and day 8 (EOT VISIT); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of serum human beta defensin-2 (hBD-2) between days 1 and 8 Time: Day 1 to day 8Description: Change of rhinopharynx levels of interleukin-6 (IL-6) of enrolled patients between day 1, day 4 and day8 (EOT visit); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of cytokine levels interleukin-6 (IL-6) at the rhinopharynx between days 1,4 and 8 Time: Day 1 to day 8Description: Change of rhinopharynx levels of interleukin-1 (IL-1) of enrolled patients between day 1, day 4 and day8 (EOT visit); this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of interleukin-1 (IL-1) cytokine levels at the rhinopharynx between days 1,4 and 8 Time: Day 1 to day 8Description: Comparison of the Interleukin-10/Tumor Necrosis Factor α (IL-10/TNFα) ratio in enrolled patients at days 1 and 8; this is also analyzed separately for patients with upper and with lower respiratory tract infection
Measure: Change of the IL-10/TNFα ratio between days 1 and 8 Time: Day 1 to Day 8In December 2019, Coronavirus infection (COVID-19) was identified as causing serious respiratory infection in humans. Initially COVID-19 was propagated by infected symptomatic individuals; currently the disease is disseminated by asymptomatic COVID-19 positive subjects. The prevalence of asymptomatic COVID-19 individuals is unknown. Due its physiologic immune suppression, pregnancy is a vulnerable time for severe respiratory infections including COVID-19. Limited information is available regarding the impact of COVID-19 in pregnancy and the prevalence and demographic profile of asymptomatic pregnant women. Despite reports of 15-20% positive COVID-19 tests in women admitted to Labor and Delivery, professional obstetric medical societies still recommend not prioritizing testing of patients who are asymptomatic. In the USA, COVID-19 symptomatic patients come predominantly from lower income, Black and Latino communities. No data are available on the rate and demographic distribution of asymptomatic positive COVID-19 pregnant women. To minimize the risk of inadvertent exposure asymptomatic individuals, recently our institution started COVID-19 testing in all admitted pregnant women. The investigators expect to gain knowledge on the impact of COVID-19 in pregnant women especially if asymptomatic and compare to other respiratory infections.
Description: Rate of asymptomatic pregnant women who test positive for COVID-19 at the time of hospital admission
Measure: Asymptomatic COVID-19 positive pregnant women Time: Through completion of the study, an average of 1 yearDescription: Rate of Hispanic pregnant women among those asymptomatic COVID-19 positive on admission
Measure: Asymptomatic Hispanic COVID-19 positive pregnant women Time: Through completion of the study, an average of 1 yearDescription: Rate of asymptomatic positive pregnant women who later will develop COVID-19 related symptoms
Measure: Follow up of asymptomatic COVID-19 positive pregnant women Time: Through completion of the study, an average of 1 yearDescription: Prevalence of COVID-19 positive newborns from infected mothers
Measure: COVID-19 positive newborns Time: Through completion of the study, an average of 1 yearDescription: Rate of COVID-19 positive pregnant women who develop respiratory / multi-organ complications requiring admission to Medicine or Intensive Care units / maternal death related to COVID-19
Measure: Severe COVID-19 disease in pregnant women Time: Through completion of the study, an average of 1 yearCoronavirus has already infected 4,673,809 people and killed 312,646 people worldwide, and no specific treatment or a vaccine against it has yet proven to be effective. Ozone therapy has become o promising tool for both prevention and treatment of COVID-19 infection by various possible mechanisms. The oxidative stress created by ozone in the body to stimulate the peripheral phagocytic cells, activate the antioxidant system, and restore the immune system is thought to be effective for the prevention of COVID-19 infection. In recent years, ozone therapy has become a popular alternative method for chronic pain management of various diseases such as fibromyalgia, knee osteoarthritis, and rheumatic diseases. As a result of this, there were many individuals who had received ozone therapy before the outbreak of COVID-19. This study aimed to investigate the preventive effect of ozone therapy against COVID-19 infection in these individuals.
Description: It involved questions about age, gender, height, weight, occupation, comorbidities, and concurrent medications, in addition to a detailed query for COVID-19 infection
Measure: The survey that was taken by telephone calls Time: Day 0Professionals and residents of nursing homes are one of the most vulnerable groups in this public health crisis of COVID-19, since they have the highest rate of positives for COVID-19, despite the restriction measures carried out, such as prohibition of family visits to these centers, the infection occurs by cross transmission with the care staff of the centers, or with other residents. At the moment, there are no clinical trials to test the hypothesis that hydroxychloroquine is effective in coronavirus treatment. Although what has been observed is a better prognosis in infected patients, since this drug inhibits the replication of the virus and its expansion to other tissues. This study is a clinical trial to test the effectiveness of hydroxychloroquine as a preventive drug for SARS-CoV-2 infection. This drug will be applied to 1050 people residing in nursing home care and 880 professionals who work in close contact with these people and who have not yet contracted the infection. This project will be carried out in the territories of Madrid, Navarra, Aragon and Andalusia (Spain). Hydroxychloroquine is a widely known drug that is used in two scenarios, against autoimmune diseases, such as lupus or rheumatoid arthritis, and as an antimalarial drug. It is also intended to demonstrate that the presumed reduction in viral load that would be obtained with hydroxychloroquine prophylaxis, would have no effect in development of immunity against the virus. This fact can create a new paradigm for the de-escalation of the confinement to which the population has been subjected to stop the virus spread, allowing the development of general immunity in controlled populations until reaching total immunity. In addition to testing the effect of this drug, a non-pharmacological intervention based on a safety record will be tested in the management of infection on nursing home, to assess its effectiveness in detecting risk areas or bad practices carried out in this vulnerable environment. The study is led by researchers of the Institute of Biomedicine of Malaga (Spain), and has obtained a financing of 1,024,199 euros from Carlos III Health Institute (Spain). The period of execution of the clinical trial is one year, and with this intervention, the intention is to reduce cross-infection in residents by a minimum threshold of 15%, as well as to decrease infection in the professionals.
Description: Discrete quantitative variable. Residents with active viral load (diagnosed by polymerase chain reaction test) will be considered infected.
Measure: Number of secondary cases of SARS-CoV2 infection among residents at six days Time: This outcome will be evaluated at six days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Discrete quantitative variable. Residents with active viral load (diagnosed by polymerase chain reaction test) will be considered infected.
Measure: Number of secondary cases of SARS-CoV2 infection among residents at 14 days Time: This outcome will be evaluated at 14 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Discrete quantitative variable. Residents with active viral load (diagnosed by polymerase chain reaction test) will be considered infected.
Measure: Number of secondary cases of SARS-CoV2 infection among residents at 28 days Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable
Measure: SARS-CoV-2 infection in nursing home staff who provide direct care at six days Time: This outcome will be evaluated at six days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable
Measure: SARS-CoV-2 infection in nursing home staff who provide direct care at 14 days Time: This outcome will be evaluated at 14 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable
Measure: SARS-CoV-2 infection in nursing home staff who provide direct care at 28 days Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous qualitative variable (1: Death 0: Survival)
Measure: Mortality Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Continous variable. It will be evaluated with the AIDS Clinical Trials Group method: investigation of medications not taken in a period of 4 days prior to the interview)% adherence = (total prescribed galenic units for that period-total units not taken) / total prescribed galenic units for that period
Measure: Compliance with treatment Time: It will be evaluated during the five days that the chemoprophylaxis with hydorxychloroquine is administeredDescription: Dichotomous categorical variable. The participant presents symptoms compatible with SARS-CoV-2 infection. High temperature, cephalea, dyspnea,diarrhea, vomiting, arthro-myalgia, pharynx pain, abdominal pain, anosmia, cough.
Measure: Symptoms of SARS-CoV-2 infection at six days Time: This outcome will be evaluated at 6 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable. The participant presents symptoms compatible with SARS-CoV-2 infection. High temperature, cephalea, dyspnea,diarrhea, vomiting, arthro-myalgia, pharynx pain, abdominal pain, anosmia, cough.
Measure: Symptoms of SARS-CoV-2 infection at 14 days Time: This outcome will be evaluated at 14 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable. The participant presents symptoms compatible with SARS-CoV-2 infection. High temperature, cephalea, dyspnea,diarrhea, vomiting, arthro-myalgia, pharynx pain, abdominal pain, anosmia, cough.
Measure: Symptoms of SARS-CoV-2 infection at 28 days Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Dichotomous categorical variable. Participant requires hospital admission attributable to SARS-CoV-2 infection
Measure: Hospitalization Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Polycotomic categorical variable. Collected by clinical interview and also monitored simultaneously by external trial monitors
Measure: Adverse events at six days Time: This outcome will be evaluated at six days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Polycotomic categorical variable. Collected by clinical interview and also monitored simultaneously by external trial monitors
Measure: Adverse events at 14 days Time: This outcome will be evaluated at 14 days from the administration of chemoprophylaxis with hydroxychloroquineDescription: Polycotomic categorical variable. Collected by clinical interview and also monitored simultaneously by external trial monitors
Measure: Adverse events at 28 days Time: This outcome will be evaluated at 28 days from the administration of chemoprophylaxis with hydroxychloroquine