Correlated Drug Terms (259)

---

	Name (Synonyms)	Correlation
drug360	Hydroxychloroquine Wiki	0.25
drug616	Placebo Wiki	0.22
drug304	Favipiravir Wiki	0.17
drug242	DAS181 Wiki	0.17
drug375	Hydroxychloroquine Sulfate Wiki	0.16
drug627	Placebo oral tablet Wiki	0.15
drug429	Interferon Beta-1B Wiki	0.14
drug60	Ascorbic Acid Wiki	0.14
drug480	Losartan Wiki	0.13
drug46	Anakinra Wiki	0.13
drug650	Presatovir Wiki	0.12
drug364	Hydroxychloroquine + azithromycin Wiki	0.12
drug597	PUL-042 Inhalation Solution Wiki	0.12
drug330	HB-adMSCs Wiki	0.12
drug632	Placebos Wiki	0.11
drug361	Hydroxychloroquine (HCQ) Wiki	0.10
drug222	Control group Wiki	0.10
drug980	methylprednisolone therapy Wiki	0.08
drug328	Guided online support program Wiki	0.08
drug93	BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki	0.08
drug664	Pyridostigmine Bromide Wiki	0.08
drug166	CYNK-001 Wiki	0.08
drug766	Standard Plasma (FFP) Wiki	0.08
drug700	Risk of MERS infection Wiki	0.08
drug294	Examine the impact of COVID-19 during pregnancy Wiki	0.08
drug539	Naso pharyngeal swab Wiki	0.08
drug476	Lopinavir and ritonavir Wiki	0.08
drug295	Exercise brochure Wiki	0.08
drug510	Mid dose chloroquine or hydroxychloroquine Wiki	0.08
drug760	Standar of care Wiki	0.08
drug1017	samling of oropharynx and nasopharynx Wiki	0.08
drug903	VivaDiag™ COVID-19 lgM/IgG Rapid Test Wiki	0.08
drug16	2: continuation of RAS blocker therapy Wiki	0.08
drug802	Surgical facial mask Wiki	0.08
drug289	Equipment with smartwatch throughout hospital stay on the general ward Wiki	0.08
drug806	Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors Wiki	0.08
drug679	Random Donor Plasma Wiki	0.08
drug425	Injection and infusion of LV-SMENP-DC vaccine and antigen-specific CTLs Wiki	0.08
drug348	High does chloroquine or hydroxychloroquine Wiki	0.08
drug824	Telephone follow-up Wiki	0.08
drug437	Interview Wiki	0.08
drug230	Convalescent plasma Wiki	0.08
drug837	The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care: Wiki	0.08
drug800	Supportive Care Wiki	0.08
drug1037	trimethoprim/sulfamethoxazole Wiki	0.08
drug292	Etoposide Wiki	0.08
drug976	mRNA-1273 Wiki	0.08
drug149	COVID-19 IgM/IgG Rapid Testing, mobile device image capture and telemedicine support Wiki	0.08
drug113	Best Practice Wiki	0.08
drug962	hydroxychloroquine in combination with camostat mesylate Wiki	0.08
drug62	Ascorbic Acid and Zinc Gluconate Wiki	0.08
drug927	azithromycin Wiki	0.08
drug729	Saliva Wiki	0.08
drug630	Placebo: Emtricitabine/tenofovir disoproxil Placebo Wiki	0.08
drug277	Eicosapentaenoic acid gastro-resistant capsules Wiki	0.08
drug943	collection of biological samples Wiki	0.08
drug501	Melatonin 2mg Wiki	0.08
drug792	Sterile Normal Saline for Intravenous Use Wiki	0.08
drug282	Emtricitabine/tenofovir disoproxil Wiki	0.08
drug604	Peginterferon Lambda-1a Wiki	0.08
drug624	Placebo of Hydroxychloroquine Wiki	0.08
drug421	Inhaled Supplemental Oxygen Wiki	0.08
drug684	Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki	0.08
drug544	New screening strategy Wiki	0.08
drug193	Chloroquine analog (GNS651) Wiki	0.08
drug1019	serological test Wiki	0.08
drug320	Ganovo+ritonavir+/-Interferon nebulization Wiki	0.08
drug845	Thrombin Generation Assay (TGA) Wiki	0.08
drug354	Human biological samples Wiki	0.08
drug346	Hidroxicloroquina + Azitromicina o Lopinavir/ritonavir + Interferon β-1b + Hidroxicloroquina Wiki	0.08
drug246	Danoprevir+Ritonavir Wiki	0.08
drug183	Centricyte 1000 Wiki	0.08
drug972	lopinavir/ritonavir Wiki	0.08
drug372	Hydroxychloroquine Oral Product Wiki	0.08
drug405	Hyperimmune plasma Wiki	0.08
drug841	There is no intervention in this study Wiki	0.08
drug270	Drug Isotretinoin (13 cis retinoic acid ) capsules+standard treatment Wiki	0.08
drug1039	vaccine BCG Wiki	0.08
drug745	Serum testing Wiki	0.08
drug847	Thrombomodulin Modified Thrombin Generation Assay (TGA-TM) Wiki	0.08
drug734	Satisfaction evaluation Wiki	0.08
drug284	Enoxaparin Wiki	0.08
drug930	bidirectional oxygenation mouthpiece Wiki	0.08
drug475	Lopinavir and Ritonavir Tablets Wiki	0.08
drug380	Hydroxychloroquine Sulfate 200 MG [Plaquenil] Wiki	0.08
drug605	Peginterferon lambda alfa-1a subcutaneous injection Wiki	0.08
drug681	Rapid molecular test Wiki	0.08
drug271	Duodenal biopsy Wiki	0.08
drug721	SLEDD with a L-MOD Wiki	0.08
drug785	Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection Wiki	0.08
drug369	Hydroxychloroquine - Daily dosing Wiki	0.08
drug743	Serum SARs COV 2 IGg screening in health care workers Wiki	0.08
drug915	Zinc Wiki	0.08
drug280	Elisa-test for IgM and IgG to SARS-CoV-2 Wiki	0.08
drug154	COVID-19 convalescent plasma Wiki	0.08
drug373	Hydroxychloroquine Pre-Exposure Prophylaxis Wiki	0.08
drug494	Matched Placebo Hydroxychloroquine Wiki	0.08
drug227	Convalescent Plasma Transfusion Wiki	0.08
drug1020	serum chemistry analysis Wiki	0.08
drug419	Indomethacin Wiki	0.08
drug236	CoronaCideTM COVID-19 IgM/IgG Rapid Test and Premier Biotech COVID-19 IgM/IgG Rapid Test Wiki	0.08
drug318	GO2 PEEP MOUTHPIECE Wiki	0.08
drug916	Zinc Gluconate Wiki	0.08
drug363	Hydroxychloroquine + Placebo Wiki	0.08
drug3	- Synthetic anti-malarial drugs Wiki	0.08
drug191	Chloroquine Diphosphate Wiki	0.08
drug585	Outpatient MRI Wiki	0.08
drug859	Tradipitant Wiki	0.08
drug244	DAS181 OL Wiki	0.08
drug10	1: discontinuation of RAS blocker therapy Wiki	0.08
drug864	Treatment with Dexmedetomidine Wiki	0.08
drug784	Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation Wiki	0.08
drug345	Hidroxicloroquina Wiki	0.08
drug918	Zithromax Oral Product Wiki	0.08
drug780	Standard screening strategy Wiki	0.08
drug720	SARS-Cov2 testing Wiki	0.08
drug411	IgM and IgG diagnostic kits to SARS-CoV-2 Wiki	0.08
drug920	additional blood tubes Wiki	0.08
drug1043	washed microbiota transplantation Wiki	0.08
drug125	Biosensors Wiki	0.08
drug409	IV Deployment Of cSVF In Sterile Normal Saline IV Solution Wiki	0.08
drug201	Clazakizumab 25 mg Wiki	0.08
drug200	Clazakizumab 12.5 mg Wiki	0.08
drug963	hydroxychloroquine placebo Wiki	0.08
drug625	Placebo of LPV/r Tablets Wiki	0.08
drug118	BioMedomics COVID-19 IgM-IgG Rapid Test Wiki	0.08
drug1026	standard operating procedures Wiki	0.08
drug715	SARS-CoV-2 IgG Antibody Testing Kit Wiki	0.08
drug573	Observational Study Wiki	0.08
drug926	artus Influenza A/B RT-PCR Test Wiki	0.08
drug424	Inhaled nitric oxide gas Wiki	0.08
drug412	Imatinib Wiki	0.08
drug158	COVID-19 test, polymerase chain reaction for SARS-CoV-2 Wiki	0.08
drug545	Next generation Sequencing (NGS) analysis Wiki	0.08
drug786	Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation Wiki	0.08
drug985	muscle ultrasound Wiki	0.08
drug250	Data collection and rhinopharyngeal swab Wiki	0.08
drug463	Liberase Enzyme (Roche) Wiki	0.08
drug971	laboratory biomarkers Wiki	0.08
drug301	Extra blood sample Wiki	0.08
drug578	Online Survey Wiki	0.08
drug483	Low-dose chloroquine/hydroxychloroquine Wiki	0.08
drug377	Hydroxychloroquine Sulfate + Azithromycin Wiki	0.08
drug297	Experimental: Questionnaire without precaution information Wiki	0.08
drug651	Presatovir placebo Wiki	0.08
drug305	Favipiravir + Standard of Care Wiki	0.08
drug968	identify SARS-CoV-2 infection by serology Wiki	0.08
drug852	To assess for development of IgG antibodies against SARS-CoV2 Wiki	0.08
drug122	Biological: COVID-19 convalescent plasma Wiki	0.08
drug902	Vitamins Wiki	0.08
drug252	Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days Wiki	0.08
drug446	Isotretinoin(Aerosolized 13 cis retinoic acid) +standard treatment Wiki	0.08
drug278	Electric pad for human external pain therapy Wiki	0.08
drug450	JNJ-53718678 Wiki	0.08
drug422	Inhaled beclomethasone Wiki	0.08
drug468	Loop mediated isothermal amplification COVID-19 Wiki	0.08
drug698	Ribavirin Wiki	0.08
drug352	Huaier Granule Wiki	0.08
drug51	Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) Wiki	0.08
drug631	Placebo: Hydroxychloroquine Wiki	0.08
drug338	HOME-CoV rule implementation Wiki	0.08
drug931	biological samples collection Wiki	0.08
drug974	lopinavir/ritonavir tablets or Arbidol or chloroquine phosphate Wiki	0.08
drug281	Emapalumab Wiki	0.08
drug670	Questionnaire with precaution information Wiki	0.08
drug749	Simvastatin Wiki	0.08
drug237	Covid-19 Antibody testing (IgG and IgM) Wiki	0.08
drug619	Placebo 250 cc 24 hours continuous infusion for 15 days Wiki	0.08
drug350	Honey Wiki	0.08
drug919	a specifically designed self-administered questionnaire Wiki	0.08
drug1028	standard therapy Wiki	0.08
drug177	Carrimycin Wiki	0.08
drug349	High-Titer COVID-19 Convalescent Plasma (HT-CCP) Wiki	0.08
drug362	Hydroxychloroquine + Azithromycin Wiki	0.08
drug204	Clinical examination Wiki	0.08
drug1006	prayer Wiki	0.08
drug240	Cytokine profile Wiki	0.08
drug787	Standard therapy recommended by the Ministry of Health of the Russian Federation. Wiki	0.08
drug334	HCQ + Intravenous Famotidine Wiki	0.08
drug778	Standard of care treatment Wiki	0.08
drug321	Gargle/Mouthwash Wiki	0.08
drug904	WHO recommendations (waiting condition) Wiki	0.08
drug393	Hydroxychloroquine in combination of Azithromycin Wiki	0.08
drug935	blood samples Wiki	0.08
drug556	Nivolumab Injection Wiki	0.08
drug1015	remdesivir Wiki	0.08
drug598	Pacebo: Calcium citrate Wiki	0.08
drug63	Aspirin Wiki	0.08
drug290	Ergoferon Wiki	0.08
drug9	1: Usual practice Wiki	0.08
drug15	2: Usual practice + SYMBICORT RAPIHALER Wiki	0.08
drug560	No intervention, observational study Wiki	0.08
drug339	Halo Oral Spray Wiki	0.08
drug725	Saline Wiki	0.08
drug905	WJ-MSCs Wiki	0.08
drug1012	quetionnary Wiki	0.08
drug291	Escin Wiki	0.08
drug376	Hydroxychloroquine Sulfate (HCQ) Wiki	0.08
drug618	Placebo + Placebo Wiki	0.08
drug553	Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki	0.08
drug335	HCQ + Placebo Wiki	0.08
drug120	Biological samples specific to research Wiki	0.08
drug296	Experimental drug Wiki	0.08
drug547	Nigella Sativa / Black Cumin Wiki	0.08
drug509	Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF) Wiki	0.08
drug340	Halo Placebo Wiki	0.08
drug243	DAS181 COVID-19 Wiki	0.08
drug379	Hydroxychloroquine Sulfate 200 MG Wiki	0.08
drug333	HCQ & AZ Wiki	0.08
drug478	Lopinavir/ritonavir Wiki	0.08
drug691	Remdesivir Wiki	0.07
drug900	Vitamin C Wiki	0.07
drug854	Tocilizumab Wiki	0.06
drug533	NORS (Nitric Oxide Releasing Solution) Wiki	0.06
drug555	Nivolumab Wiki	0.06
drug946	convalescent plasma Wiki	0.06
drug269	Doxycycline Wiki	0.06
drug552	Nitric Oxide Wiki	0.06
drug828	Telmisartan Wiki	0.06
drug538	Nasal swab Wiki	0.06
drug558	No intervention Wiki	0.06
drug370	Hydroxychloroquine - Weekly Dosing Wiki	0.06
drug317	GLS-5300 Wiki	0.06
drug386	Hydroxychloroquine Sulfate Regular dose Wiki	0.06
drug58	Arbidol Wiki	0.06
drug692	Remdesivir placebo Wiki	0.06
drug196	Chloroquine phosphate Wiki	0.06
drug738	Selinexor Wiki	0.06
drug276	Eculizumab Wiki	0.06
drug1018	self-administered questionnaire Wiki	0.06
drug775	Standard of care Wiki	0.06
drug540	Nasopharyngeal swab Wiki	0.06
drug130	Blood draw Wiki	0.06
drug929	basic treatment Wiki	0.06
drug799	Sulfonated tetra-anthracenyl porphyrin Wiki	0.06
drug313	Follow up Wiki	0.06
drug192	Chloroquine Sulfate Wiki	0.06
drug385	Hydroxychloroquine Sulfate Loading Dose Wiki	0.06
drug771	Standard of Care Wiki	0.06
drug82	Azithromycin Wiki	0.05
drug925	anti-SARS-CoV-2 convalescent plasma Wiki	0.05
drug554	Nitric Oxide Gas Wiki	0.05
drug901	Vitamin D Wiki	0.05
drug823	Telemedicine Wiki	0.05
drug788	Standard treatment Wiki	0.05
drug169	Camostat Mesilate Wiki	0.05
drug960	hydroxychloroquine Wiki	0.05
drug469	Lopinavir / Ritonavir Wiki	0.05
drug428	Interferon Beta-1A Wiki	0.05
drug769	Standard care Wiki	0.04
drug936	blood sampling Wiki	0.04
drug826	Telerehabilitation Wiki	0.04
drug668	Questionnaire Wiki	0.04
drug582	Oseltamivir Wiki	0.04
drug190	Chloroquine Wiki	0.03
drug753	SnPP Protoporphyrin Wiki	0.03
drug732	Sarilumab Wiki	0.03
drug1003	placebo Wiki	0.03
drug225	Convalescent Plasma Wiki	0.03

Correlated MeSH Terms (64)

---

	Name (Synonyms)	Correlation
D003141	Communicable Diseases NIH	0.68
D045169	Severe Acute Respiratory Syndrome NIH	0.36
D014777	Virus Diseases NIH	0.32
D018352	Coronavirus Infections NIH	0.29
D012141	Respiratory Tract Infections NIH	0.19
D018357	Respiratory Syncytial Virus Infections NIH	0.17
D003333	Coronaviridae Infections NIH	0.14
D012327	RNA Virus Infections NIH	0.12
D029424	Pulmonary Disease, Chronic Obstructive NIH	0.10
D018184	Paramyxoviridae Infections NIH	0.10
D007251	Influenza, Human NIH	0.09
D006470	Hemorrhage NIH	0.08
D003384	Coxsackievirus Infections NIH	0.08
D004660	Encephalitis NIH	0.08
D006929	Hyperaldosteronism NIH	0.08
D003428	Cross Infection NIH	0.08
D014552	Urinary Tract Infections NIH	0.08
D054990	Idiopathic Pulmonary Fibrosis NIH	0.08
D009362	Neoplasm Metastasis NIH	0.08
D000309	Adrenal Insufficiency NIH	0.08
D054559	Hyperphosphatemia NIH	0.08
D007154	Immune System Diseases NIH	0.08
D011649	Pulmonary Alveolar Proteinosis NIH	0.08
D007008	Hypokalemia NIH	0.08
D009410	Nerve Degeneration NIH	0.08
D007676	Kidney Failure, Chronic NIH	0.08
D017250	Caliciviridae Infections NIH	0.08
D008173	Lung Diseases, Obstructive NIH	0.08
D008171	Lung Diseases, NIH	0.08
D001997	Bronchopulmonary Dysplasia NIH	0.08
D011565	Psoriasis NIH	0.08
D055501	Macrophage Activation Syndrome NIH	0.08
D009220	Myositis NIH	0.08
D008595	Menorrhagia NIH	0.08
D009205	Myocarditis NIH	0.08
D011024	Pneumonia, Viral NIH	0.07
D011014	Pneumonia NIH	0.06
D012140	Respiratory Tract Diseases NIH	0.06
D009369	Neoplasms, NIH	0.06
D030341	Nidovirales Infections NIH	0.06
D020521	Stroke NIH	0.06
D003139	Common Cold NIH	0.06
D058070	Asymptomatic Diseases NIH	0.06
D003324	Coronary Artery Disease NIH	0.06
D000257	Adenoviridae Infections NIH	0.06
D053120	Respiratory Aspiration NIH	0.06
D019337	Hematologic Neoplasms NIH	0.05
D004211	Disseminated Intravascular Coagulation NIH	0.05
D011658	Pulmonary Fibrosis NIH	0.05
D011665	Pulmonary Valve Insufficiency NIH	0.05
D004417	Dyspnea NIH	0.05
D016638	Critical Illness NIH	0.04
D017563	Lung Diseases, Interstitial NIH	0.04
D012120	Respiration Disorders NIH	0.04
D020141	Hemostatic Disorders NIH	0.04
D001778	Blood Coagulation Disorders NIH	0.04
D055371	Acute Lung Injury NIH	0.04
D012127	Respiratory Distress Syndrome, Newborn NIH	0.04
D006973	Hypertension NIH	0.04
D012128	Respiratory Distress Syndrome, Adult NIH	0.03
D018450	Disease Progression NIH	0.03
D000860	Hypoxia NIH	0.03
D013577	Syndrome NIH	0.03
D002318	Cardiovascular Diseases NIH	0.02

Correlated HPO Terms (8)

---

	Name (Synonyms)	Correlation
HP:0011947	Respiratory tract infection HPO	0.14
HP:0000132	Menorrhagia HPO	0.08
HP:0002900	Hypokalemia HPO	0.08
HP:0000859	Hyperaldosteronism HPO	0.08
HP:0000846	Adrenal insufficiency HPO	0.08
HP:0000822	Hypertension HPO	0.06
HP:0002098	Respiratory distress HPO	0.06
HP:0002090	Pneumonia HPO	0.05

Primary Outcomes

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 14

---

Primary Outcomes

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.

---

Primary Outcomes

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 days

---

Description: • Cmax, Tmax, AUC, apparent volume of distribution, clearance, terminal elimination half-life

Measure: Pharmacokinetics of Oseltamivir

Time: Day 0 and Day 9

---

Secondary Outcomes

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Primary Outcomes

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 recruitment

---

Primary Outcomes

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 5

---

Secondary Outcomes

Description: 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 5

---

Measure: Number of Hospitalization-Free Days Following Presatovir Administration

Time: Up to Day 28

---

Description: 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 28

---

Primary Outcomes

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 9

---

Description: 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 28

---

Secondary Outcomes

Description: 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 28

---

Primary Outcomes

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 9

---

Secondary Outcomes

Measure: Number of Supplemental O2-Free Days Through Day 28

Time: Up to Day 28

---

Measure: Percentage of Participants Developing Respiratory Failure Requiring Mechanical Ventilation Through Day 28

Time: Up to Day 28

---

Measure: Percentage of All-Cause Mortality Among Participants Through Day 28

Time: Up to Day 28

---

Primary Outcomes

Measure: Freedom from new or progressive chronic lung allograft dysfunction

Time: 180 days

---

Measure: Death

Time: 180 days

---

Secondary Outcomes

Measure: Respiratory virus symptom score

Time: 7 days

---

Measure: Acute rejection

Time: 180 days

---

Measure: Lymphocytic bronchiolitis

Time: 180 days

---

Measure: Donor-specific antibodies

Time: 180 days

---

Measure: Chronic lung allograft dysfunction

Time: 365 days

---

Primary Outcomes

Measure: Numbers of infected patient

Time: Serologic confimred MERS case within 4 weeks after contacting to a case patients

---

Primary Outcomes

Measure: The number of new viruses and/or bacteria identified and characterized by respiratory and pharyngeal carriage among pilgrims between the departure and the return of Hajj

Time: up to 3 years

---

Primary Outcomes

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).

Measure: Time to Alleviation of All ARVI Symptoms.

Time: 14 days of observation.

---

Secondary Outcomes

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). The higher values represent 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 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.

---

Primary Outcomes

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 Days

---

Secondary Outcomes

Description: 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 26

---

Description: 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 26

---

Description: 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 26

---

Other Outcomes

Description: 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 26

---

Description: Measured by death from all causes

Measure: Efficacy in reduction of mortality

Time: Day 26

---

Description: Assessed by time to negative conversion of COVID-19 RT-PCR from upper respiratory tract

Measure: Antiviral effect

Time: Day 26

---

Description: Time to clinical recovery as measured by resolution of clinical signs

Measure: Efficacy on clinical improvement

Time: Day 26

---

Description: Measured by change in the Modified Jackson Cold Score

Measure: Efficacy on the respiratory symptoms

Time: Day 26

---

Primary Outcomes

Description: Viability of enteroids as determined by microscopy

Measure: Establishment of human intestinal stem cell-derived enteroids

Time: An average of three months

---

Primary Outcomes

Description: Removal of all oxygen support (with stable SpO2)

Measure: Percent of subjects who Return to Room Air (RTRA) (main study)

Time: by Day 28

---

Measure: Percent of subjects with improved COVID-19 Clinical Status Scale (sub-study)

Time: Day 14

---

Secondary Outcomes

Measure: All-cause mortality rate (main study)

Time: at Day 28

---

Measure: Percent of subjects who Return to Room Air (RTRA) (main study)

Time: by Day 21

---

Measure: Time (in days) to RTRA (main study)

Time: Days 10, 14, 21, 28

---

Measure: Percent of subjects who achieve clinical stability (main study)

Time: by Day 28

---

Measure: Percent of subjects discharged (without mortality and hospice) (main study)

Time: by Days 14, 21, 28 and 35

---

Measure: Time (in days) to first hospital discharge (without hospice) (main study)

Time: through Day 35

---

Measure: Total number of inpatient days (main study)

Time: up to Day 35

---

Measure: Baseline SAD-RV infection-related mortality rate (main study)

Time: at Day 28

---

Measure: Baseline SAD-RV infection-related mortality rate (main study)

Time: at Day 35

---

Measure: All-cause mortality rate (main study)

Time: at Day 35

---

Measure: Change in pulmonary function (FEV1% predicted) (main study)

Time: Day 1, Day 7, Day 14, Day 28

---

Measure: Time to improved COVID19 clinical status (Sub-study)

Time: Day 5, Day 10, Day 21, Day 28

---

Measure: Time to RTRA

Time: Day 10, Day 14, Day 21, Day 28

---

Measure: Time to Clinical stability

Time: Day 14, Day 21, Day 28

---

Measure: Time to SARS-CoV-2 RNA in the respiratory specimens being undetectable

Time: Day 5, Day 10, Day 14, Day 21, Day 28

---

Measure: Time to Clinical deterioration

Time: Day 5, Day 10, Day 14, Day 21, Day 28

---

Measure: Time to Discharge from hospital (without readmission before Day 28).

Time: Day 14, Day 21, Day 28

---

Measure: Time to Death (all causes)

Time: Day 14, Day 21, Day 28

---

Primary Outcomes

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 years

---

Primary Outcomes

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 28

---

Secondary Outcomes

Description: 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 28

---

Description: 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 Days

---

Description: Percentage of participants with abnormal clinical laboratory findings will be reported.

Measure: Percentage of Participants with Abnormal Clinical Laboratory Findings

Time: Up to 49 days

---

Description: Percentage of participants with abnormal ECGs findings will be reported.

Measure: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings

Time: Up to 49 days

---

Description: Percentage of participants with abnormal vital signs findings will be reported.

Measure: Percentage of Participants with Abnormal Vital Signs Findings

Time: Up to 49 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: Number of supplemental O2 free days will be reported.

Measure: Number of Supplemental Oxygen (O2) Free Days Through Day 28

Time: Through Day 28

---

Description: Incidence of supplemental oxygen requirement in participants will be reported.

Measure: Incidence of Supplemental Oxygen Requirement

Time: Up to 28 days

---

Description: Duration of supplemental oxygen requirement in participants will be reported.

Measure: Duration of Supplemental Oxygen

Time: Up to 28 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: Total length of hospital stay (time in hospital from first dosing) will be reported.

Measure: Total Length of Hospital Stay

Time: Up to 49 days

---

Description: 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 days

---

Description: 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 days

---

Description: Incidence of respiratory AEs will be reported.

Measure: Incidence of Respiratory AEs

Time: Up to 49 days

---

Description: Incidence of thoracic-related AEs will be reported.

Measure: Incidence of Thoracic-related AEs

Time: Up to 49 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 28

---

Description: 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 days

---

Description: 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 28

---

Description: 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 28

---

Description: 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 8

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 28

---

Description: 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 28

---

Description: 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 days

---

Description: 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 days

---

Description: 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 28

---

Description: 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 28

---

Description: 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 days

---

Primary Outcomes

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 randomization

---

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: 14 days after randomization

---

Secondary Outcomes

Description: 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 randomization

---

Description: 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 randomization

---

Description: Percentage of patients requiring Mechanical ventilation support

Measure: Mechanical ventilation support

Time: 7 days after randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: Percentage of patients requiring Mechanical ventilation support

Measure: Mechanical ventilation support

Time: 14 days after randomization

---

Description: Clearance of noval coronavirus in upper respiratory tract or lower respiratory tract

Measure: Clearance of noval coronavirus

Time: 14 days after randomization

---

Description: All-cause mortality

Measure: All-cause mortality

Time: 30 days after randomization

---

Primary Outcomes

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 weeks

---

Primary Outcomes

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 21

---

Secondary Outcomes

Description: Body temperature will be followed everyday during time frame.

Measure: The disease prorogation-temperature

Time: Day 0 till day 21

---

Description: Respiratory rate will be followed everyday during time frame.

Measure: The disease prorogation-respiratory function 1

Time: Day 0 till day 21

---

Description: Oxygen saturation of blood will be followed everyday during time frame.

Measure: The disease prorogation-respiratory function 2

Time: Day 0 till day 21

---

Description: Chest imaging will be taken at each time point.

Measure: The disease prorogation-respiratory function 3

Time: Day 0, 4, 7, 10, 14 and 21

---

Other Outcomes

Description: Blood pressure and heart rate will be followed everyday during time frame.

Measure: Patients health condition-routine test

Time: Day 0 till day 21

---

Description: 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 21

---

Description: 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 21

---

Description: 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 21

---

Description: 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 21

---

Primary Outcomes

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 months

---

Description: 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 months

---

Description: 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 months

---

Description: 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 months

---

Description: Identify host genetic variants associated with disease progression or severity

Measure: Host genetic variants

Time: Day 1

---

Primary Outcomes

Description: Percentage

Measure: The cure rate of 2019-nCoV.

Time: 6 months

---

Description: Percentage

Measure: The improvement rate of 2019-nCoV.

Time: 6 months

---

Measure: The incidence of long-term adverse outcomes.

Time: 6 months

---

Secondary Outcomes

Description: Days

Measure: Duration of fever

Time: 2 weeks

---

Description: Days

Measure: Duration of respiratory symptoms

Time: 2 weeks

---

Description: Days

Measure: Duration of hospitalization

Time: 2 weeks

---

Measure: Number of participant(s) need intensive care

Time: 2 weeks

---

Measure: Number of participant(s) with acute respiratory distress syndrome

Time: 2 weeks

---

Measure: Number of participant(s) with extra-pulmonary complications, including shock, renal failure, multiple organ failure, hemophagocytosis syndrome, et al.

Time: 2 weeks

---

Measure: Number of participant(s) who died during the trial

Time: 10 months

---

Primary Outcomes

Description: Time to negative NPS 2019-n-CoV RT-PCR

Measure: Time to negative NPS

Time: Up to 1 month

---

Secondary Outcomes

Description: Time to negative saliva 2019-n-CoV RT-PCR

Measure: Time to negative saliva

Time: Up to 1 month

---

Description: Time to NEWS of 0

Measure: Time to clinical improvement

Time: Up to 1 month

---

Description: Length of hospitalisation

Measure: Hospitalisation

Time: Up to 1 month

---

Description: 30-day mortality

Measure: Mortality

Time: Up to 1 month

---

Description: Cytokine/ chemokine changes

Measure: Immune reaction

Time: up to 1 month

---

Description: Adverse events during treatment

Measure: Adverse events

Time: up to 1 month

---

Description: Time to negative NPS, saliva, urine and stool 2019-n-CoV RT-PCR

Measure: Time to negative all clinical specimens

Time: up to 1 month

---

Primary Outcomes

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 randomization

---

Description: 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 randomization

---

Secondary Outcomes

Description: Number of deaths during study follow-up

Measure: 28-day mortality

Time: Measured from Day 0 through Day 28

---

Description: 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 28

---

Description: Days that a participant spent at the hospital. Multiple hospitalizations are summed up.

Measure: Duration of hospitalization

Time: Measured from Day 0 through Day 28

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: Proportion of patients with different inflammation factors in normalization range.

Measure: Proportion of patients with normalized inflammation factors

Time: 7 and 14 days after randomization

---

Description: Frequency of vaccine/CTL Events

Measure: Frequency of vaccine/CTL Events

Time: Measured from Day 0 through Day 28

---

Description: Frequency of Serious vaccine/CTL Events

Measure: Frequency of Serious vaccine/CTL Events

Time: Measured from Day 0 through Day 28

---

Primary Outcomes

Measure: Clearance (CL) or apparent oral clearance (CL/F) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

---

Measure: Volume of distribution (V) or apparent oral volume of distribution (V/F) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

---

Measure: Elimination rate constant (ke) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

---

Measure: Half-life (t1/2) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

---

Measure: Absorption rate constant (ka) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

---

Measure: AUC (area under the curve) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

---

Measure: Maximum concentration (Cmax) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

---

Measure: Time to achieve maximum concentration (Tmax) as measured by PK sampling

Time: Data will be collected up to 90 days from the time of consent. For participants with Down Syndrome enrolling at sites designated as Down Syndrome sites, participants will be in the study for up to 210 days.

---

Primary Outcomes

Measure: The death of newborns with COVID-19

Time: The date of discharge，an average of 4 weeks after the admission

---

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 admission

---

Secondary Outcomes

Description: 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 birth

---

Description: 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 birth

---

Description: 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 weeks

---

Primary Outcomes

Description: The screening accuracy of the two screening strategies were calculated and compared.

Measure: Screening accuracy

Time: 1 month

---

Secondary Outcomes

Description: The costs of the two screening strategies were recorded. Cost-effectiveness analysis were performed and compared.

Measure: Cost-effectiveness analysis

Time: 1 month

---

Primary Outcomes

Measure: Frequency of solicited local reactogenicity adverse events (AEs)

Time: Through 7 days post-vaccination

---

Measure: Frequency of any medically-attended adverse events (MAAEs)

Time: Day 1 to Day 394

---

Measure: Frequency of any new-onset chronic medical conditions (NOCMCs)

Time: Day 1 to Day 394

---

Measure: Frequency of any serious adverse events (SAEs)

Time: Day 1 to Day 394

---

Measure: Frequency of any unsolicited adverse events (AEs)

Time: Through 28 days post-vaccination

---

Measure: Frequency of solicited systemic reactogenicity adverse events (AEs)

Time: Through 7 days post-vaccination

---

Measure: Grade of any unsolicited adverse events (AEs)

Time: Through 28 days post-vaccination

---

Measure: Grade of solicited local reactogenicity adverse events (AEs)

Time: Through 7 days post-vaccination

---

Measure: Grade of solicited systemic reactogenicity adverse events (AEs)

Time: Through 7 days post-vaccination

---

Secondary Outcomes

Measure: Geometric mean fold rise (GMFR) in IgG titer from baseline

Time: Day 1 to Day 57

---

Measure: Geometric mean titer (GMT) of antibody

Time: Day 57

---

Description: Seroconversion is defined as a 4-fold change in antibody titer from baseline

Measure: Percentage of subjects who seroconverted

Time: Day 1 to Day 57

---

Primary Outcomes

Description: Fever to normal time (day)

Measure: Fever to normal time (day)

Time: 30 days

---

Description: Pulmonary inflammation resolution time (HRCT) (day)

Measure: Pulmonary inflammation resolution time (HRCT) (day)

Time: 30 days

---

Description: 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 days

---

Primary Outcomes

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 days

---

Secondary Outcomes

Description: Mortality from all causes

Measure: Mortality

Time: 28 days

---

Description: 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 days

---

Description: 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 days

---

Primary Outcomes

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 days

---

Secondary Outcomes

Description: 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 days

---

Description: Rate of no fever

Measure: Rate of no fever

Time: 14 days

---

Description: Rate of no cough

Measure: Rate of no cough

Time: 14 days

---

Description: Rate of no dyspnea

Measure: Rate of no dyspnea

Time: 14 days

---

Description: Rate of no requiring supplemental oxygen

Measure: Rate of no requiring supplemental oxygen

Time: 14 days

---

Description: Rate of undetectable New coronavirus pathogen nucleic acid

Measure: Rate of undetectable New coronavirus pathogen nucleic acid

Time: 14 days

---

Description: Rate of mechanical ventilation

Measure: Rate of mechanical ventilation

Time: 14 days

---

Description: Rate of ICU admission

Measure: Rate of ICU admission

Time: 14 days

---

Description: Rate of serious adverse event

Measure: Rate of serious adverse event

Time: 14 days

---

Primary Outcomes

Description: Percent of subjects who have returned to room air

Measure: Percent of subjects who have returned to room air

Time: 7 days

---

Description: 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 days

---

Primary Outcomes

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 months

---

Secondary Outcomes

Description: How many patients died during the hospitalization

Measure: in-hospital mortality

Time: 1 month

---

Description: How many patients died 30 days after the discharge

Measure: 30 days mortality

Time: 1 month

---

Description: How many patients died 6 months after the discharge

Measure: 6 months mortality

Time: 6 months

---

Description: How many patients were intubated during the hospitalization

Measure: Intubation rate

Time: 7 days

---

Description: How many days/hours from admittance to intubation

Measure: Time to Intubation

Time: 7 days

---

Description: How many days/hours from admittance to the start of non invasive ventilation or CPAP therapy

Measure: Time to ventilation

Time: 7 days

---

Description: 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 days

---

Description: How many patients were healed from the infection and discharged

Measure: Recovery rate

Time: 1 month

---

Description: How many patients underwent re-infection after previous recovery from COVID19

Measure: Recurrence rate

Time: 1 month

---

Description: Assessment of the risk factors for the infection and the admission to the hospital

Measure: Risk factor for COVID19

Time: retrospective

---

Description: What serological parameter could be used as predictor of good or negative prognosis.

Measure: Blood tests and outcome

Time: 1 month

---

Description: Impact of antiviral therapy on the clinical course of the disease

Measure: Antiviral therapy

Time: 1 month

---

Description: Assessment of bacterial, fungal or other coinfections rate

Measure: Coinfections

Time: 1 month

---

Description: Impact of radiological findings on the clinical course and the outcome

Measure: Radiological findings

Time: 1 month

---

Description: Impact of ultrasound findings on the clinical course and the outcome

Measure: Ultrasound findings

Time: 1 month

---

Description: Assessment of the evidence of myocardial injury in covid19+ patients

Measure: Myocardial injury

Time: 1 month

---

Description: impact of standard therapeutic operating procedures (eg enteral nutrition, hydration, drugs) on the clinical course.

Measure: Medical management

Time: 1 month

---

Primary Outcomes

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 days

---

Description: 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 days

---

Secondary Outcomes

Description: Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.

Measure: Incidence of Hospitalization

Time: 14 days

---

Description: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.

Measure: Incidence of Death

Time: 90 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Primary Outcomes

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 days

---

Secondary Outcomes

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: Outcome reported as the mean number of days participants in each arm did not require ventilator use.

Measure: Ventilator-Free Days

Time: 28 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Primary Outcomes

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 days

---

Secondary Outcomes

Description: 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 days

---

Description: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.

Measure: Hypotension Requiring Vasopressors

Time: 10 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: Outcome reported as the number of participants who have expired at 28 days post enrollment.

Measure: 28-Day Mortality

Time: 28 days

---

Description: Outcome reported as the number of participants who have expired at 90 days post enrollment.

Measure: 90-Day Mortality

Time: 90 days

---

Description: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).

Measure: ICU Admission

Time: 10 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Primary Outcomes

Description: Percentage of subjects with COVID-19 diagnosis in the two groups

Measure: COVID-19 diagnosis

Time: 14 days

---

Secondary Outcomes

Description: Percentage of subjects with a positive test in the two groups

Measure: Positive SARS-CoV-2 rt-PCR test

Time: 14 days

---

Other Outcomes

Description: Mean/ Median in the two groups

Measure: Total number of quarantine days

Time: 14 days

---

Description: Percentage in the two groups

Measure: Proportion of healthcare providers requiring quarantine

Time: 14 days

---

Primary Outcomes

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 severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Clinical Improvement within 10 days from the start of the experimental therapy.

Measure: Severity of COVID-19

Time: 10 days

---

Secondary Outcomes

Description: SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy

Measure: SARS-CoV-2 infection

Time: 28 days

---

Description: The severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Clinical Improvement within 28 days from the start of the experimental therapy.

Measure: Severity of COVID-19 over 28 days

Time: 28 days

---

Description: The requirement for ICU admission within 28 days from the start of the experimental therapy.

Measure: ICU admission

Time: 28 days

---

Description: The requirement for mechanical ventilation within 28 days from the start of the experimental therapy.

Measure: Mechanical Ventilation

Time: 28 days

---

Description: All cause mortality at 28 days from the start of experimental therapy

Measure: Mortality

Time: 28 days

---

Primary Outcomes

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 14 days from the start of experimental therapy.

Measure: Severity of COVID-19

Time: 14 days

---

Secondary Outcomes

Description: 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 days

---

Description: 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 days

---

Description: The requirement for ICU admission within 28 days from the start of experimental therapy.

Measure: ICU admission

Time: 28 days

---

Description: The requirement for mechanical ventilation within 28 days from the start of experimental therapy.

Measure: Mechanical ventilation

Time: 28 days

---

Description: All cause mortality at 28 days from the start of experimental therapy.

Measure: Mortality

Time: 28 days

---

Primary Outcomes

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 hours

---

Secondary Outcomes

Description: 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 hours

---

Description: 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 days

---

Description: 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 randomization

---

Primary Outcomes

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 days

---

Description: 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 days

---

Description: 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 months

---

Description: 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 months

---

Description: 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 days

---

Secondary Outcomes

Description: Number of Invalid results

Measure: Reliability of the test

Time: 30 days

---

Description: Number of healthcare workers that become positive for COVID-19 IgM or IgG

Measure: Positive HCW

Time: 60 days

---

Description: Number of Chronic Patients that become positive for COVID-19 IgM or IgG

Measure: Number of Chronic Patients

Time: 60 days

---

Primary Outcomes

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)

---

Primary Outcomes

Measure: Number of participants who experience inpatient admission

Time: 2 months

---

Secondary Outcomes

Measure: Number of participants admitted to the intensive care unit

Time: 2 months

---

Measure: Number of participants requiring mechanical ventilation

Time: 2 months

---

Measure: Number of deceased participants

Time: 2 months

---

Primary Outcomes

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 days

---

Description: 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 days

---

Secondary Outcomes

Measure: Safety evaluation, as measured by AEs, Adverse Reactions (ARs), SAEs, Serious ARs (SARs)

Time: 30 days

---

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; 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 days

---

Description: Mortality

Measure: Cohort 1: Day 30 mortality

Time: 30 days

---

Description: NEWS2

Measure: Cohort 1: Change in NEW(2) score from baseline to day 30

Time: 30 days

---

Description: ICU

Measure: Cohort 1: Admission to ICU

Time: 30 days

---

Description: invasive mechanical ventilation or ECMO

Measure: Cohort 1: Use of invasive mechanical ventilation or ECMO

Time: 30 days

---

Description: Nasal or high-flow oxygen

Measure: Cohort 1: Duration of supplemental oxygen (days)

Time: 30 days

---

Description: 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 days

---

Description: No of new COVID-19 infections in the household

Measure: Cohort 2: Number participant-reported secondary infection of housemates

Time: 30 days

---

Description: Hospital admission

Measure: Cohort 2: Time to hospital admission related to COVID-19 infection

Time: 30 days

---

Primary Outcomes

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 randomization

---

Secondary Outcomes

Description: All-cause mortality rates at 29 days after randomization

Measure: All-cause mortality

Time: 29 days after randomization

---

Description: 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 randomization

---

Description: Number of days free from mechanical ventilation at 29 days after randomization

Measure: Number of days free from mechanical ventilation

Time: 29 days after randomization

---

Description: Number of days that the patient was on mechanical ventilation after randomization

Measure: Duration of mechanical ventilation

Time: 7, 15 and 29 days after randomization

---

Description: Length of hospital stay on survivors

Measure: Duration of hospitalization

Time: 7, 15 and 29 days after randomization

---

Description: Presence of other secondary infections

Measure: Other secondary infections

Time: 7, 15 and 29 days after randomization

---

Description: Time from treatment start to death

Measure: Time from treatment start to death

Time: 7, 15 and 29 days after randomization

---

Other Outcomes

Description: Occurrence of QT interval prolongation

Measure: QT interval prolongation

Time: 7, 15 and 29 days after randomization

---

Description: Occurrence of gastrointestinal intolerance

Measure: Gastrointestinal intolerance

Time: 7, 15 and 29 days after randomization

---

Description: Occurrence of laboratory albnormalities in red blood cell count, creatinine and bilirubin

Measure: Laboratory albnormalities

Time: 7, 15 and 29 days after randomization

---

Description: Occurrence of adverse events related to the use of the investigational products

Measure: Adverse events

Time: 7, 15 and 29 days after randomization

---

Primary Outcomes

Description: Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 6 points. Alive at home In the hospital without oxygen In the hospital using oxygen In the hospital using high-flow nasal catheter or non-invasive ventilation In hospital, on mechanical ventilation Dead

Measure: Evaluation of the clinical status

Time: 15 days after randomization

---

Secondary Outcomes

Description: Evaluation of the clinical status of patients on the 7th day after randomization defined by the Ordinal Scale of 6 points. Alive at home In the hospital without oxygen In the hospital using oxygen In the hospital using high-flow nasal catheter or non-invasive ventilation In hospital, on mechanical ventilation Dead

Measure: Ordinal scale in 7 days

Time: 7 days after randomization

---

Description: Need of intubation and mechanical ventilation up to the 7th day after randomization

Measure: Need of intubation and mechanical ventilation

Time: 7 days after randomization

---

Description: Use of mechanical ventilation during hospital stay

Measure: Use of mechanical ventilation during hospital stay

Time: 15 days after randomization

---

Description: Use of non-invasive ventilation up to the 7th day after randomization

Measure: Use of non-invasive ventilation

Time: 7 days after randomization

---

Description: Hospital Length of Stay

Measure: Hospital Length of Stay

Time: 28 days after randomization

---

Description: All-cause mortality rates during hospital stay

Measure: All-cause mortality

Time: 28 days after randomization

---

Description: Occurrence of thromboembolic complications such as: Deep vein thrombosis Pulmonary Embolism Stroke

Measure: Thromboembolic complications

Time: 15 days after randomization

---

Description: 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 randomization

---

Description: Positive PCR for Sars-Cov-2 at 10 days after enrollment

Measure: Presence of virus at day 10 in subset of 180 patients

Time: 10 days after randomization

---

Other Outcomes

Description: QTc interval value

Measure: Safety outcome on QTc

Time: At day 3 and 7 after enrollment

---

Primary Outcomes

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 days

---

Description: reduction of mortality

Measure: Cohort B: reduction of mortality

Time: 30 days

---

Secondary Outcomes

Measure: Cohort A Reduction of the need of time of ventilatory support

Time: 1 month

---

Measure: Cohort B Percentage of patients that undergo to tracheostomy

Time: 1 month

---

Measure: Cohort B Improvement of the lung function assessed by radiologic findings

Time: 1 month

---

Primary Outcomes

Description: All cause mortality

Measure: Mortality rate

Time: up to 30 days

---

Description: 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 days

---

Secondary Outcomes

Description: 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 days

---

Description: days

Measure: Time of hospitalization (days)

Time: up to 30 days

---

Description: days

Measure: Time of hospitalization in intensive care units

Time: up to 30 days

---

Description: forced expiratory volume at one second ,maximum voluntary ventilation at 1month，2month，3month after discharge

Measure: Pulmonary function

Time: up to 3 months after discharge

---

Primary Outcomes

Measure: Number of days alive and discharged from hospital within 14 days

Time: 14 days

---

Secondary Outcomes

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 days

---

Measure: Admitted to intensive care unit, if admitted to ICU then length of stay

Time: 14 days

---

Measure: Have used Non-invasive ventilation (NIV) during hospitalization

Time: 14 days

---

Measure: Mortality

Time: 30 days

---

Measure: Length of hospitalization

Time: 14 days

---

Measure: Days alive and discharged from hospital

Time: 30 days

---

Measure: Mortality

Time: 90 days

---

Measure: Mortality

Time: 365 days

---

Measure: Number of readmissions (all causes)

Time: 30 days

---

Measure: Number of days using non-invasive ventilation (NIV)

Time: 14 days

---

Description: Delta PaO2 measured in arterial puncture

Measure: Change in patient's oxygen partial pressure

Time: 4 days

---

Description: Delta PaCO2 measured in arterial puncture

Measure: Change in patient's carbondioxid partial pressure

Time: 4 days

---

Description: pH measured in arterial puncture

Measure: Level of pH in blood

Time: 4 days

---

Measure: Time for no oxygen supplement (or regular oxygen supplement "LTOT")

Time: 14 days

---

Primary Outcomes

Description: Defined as the proportion of patients not requiring invasive mechanical ventilation or Extracorporeal membrane oxygenation (ECMO)

Measure: Treatment success

Time: Up to Day 15

---

Secondary Outcomes

Description: Measured in days

Measure: Time to mechanical ventilation

Time: Date of randomization to date of mechanical ventilation

---

Description: Measured in total score

Measure: Change from baseline in Modified Early Warning system score

Time: Baseline, Day 15

---

Description: 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 15

---

Description: Measured in percent (%)

Measure: Change from baseline in partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2)

Time: Baseline, Day 15

---

Description: Measured in local units

Measure: Change of pH in hemogasanalysis from baseline

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change of carbon dioxide tension (pCO2) in hemogasanalysis from baseline

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change of oxygen tension (pO2) in hemogasanalysis from baseline

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change of potassium in hemogasanalysis from baseline

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change of sodium in hemogasanalysis from baseline

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change of chloride in hemogasanalysis from baseline

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change of lactic acid in hemogasanalysis from baseline

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change of hemoglobin in hemogasanalysis from baseline

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in l/min

Measure: Change from baseline in oxygen supplementation

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: 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 15

---

Description: Measured in local units

Measure: Change from baseline in Ferritin

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in lactate dehydrogenase (LDH)

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in D-dimers

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in White Blood Cells with differential counts

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in Red Blood Counts

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in Hemoglobin

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in Platelet count

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in Fibrinogen

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in Complement factors C3/C4

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in Prothrombin time

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in Cardiac troponin

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in aspartate aminotransferase (AST)

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in alanine aminotransferase (ALT)

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in total bilirubin levels

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in C-Reactive Protein

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Measured in local units

Measure: Change from baseline in Creatinine

Time: Baseline, Days 4, 7, 10, 13 and 15

---

Description: Confirmation of death

Measure: Overall survival

Time: Weeks 6 and 10

---

Description: Measured in days

Measure: Time to hospital discharge

Time: Weeks 6 and 10

---

Primary Outcomes

Measure: Point prevalence of COVID-19 infection

Time: Baseline up to 6 months

---

Secondary Outcomes

Measure: Incidence of COVID-19 infection

Time: Baseline up to 6 months

---

Measure: Percentage of subjects presenting fever or respiratory symptoms

Time: Baseline up to 6 months

---

Measure: Evaluate the relationship between COVID-19 infection and chronic pharmacological treatments

Time: Baseline up to 6 months

---

Measure: Evaluate the relationship between COVID-19 infection and comorbid medical conditions

Time: Baseline up to 6 months

---

Primary Outcomes

Description: Reporting of Adverse Events or Severe Adverse Events Assessed by CTCAE v4.0

Measure: Incidence of Treatment-Emergent Adverse Events

Time: 1 month

---

Secondary Outcomes

Description: 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 months

---

Description: Finger Pulse Oximetry taken before and after 6 minute walk on level ground, compare desaturation tendency

Measure: Digital Oximetry

Time: 3 months, 6 months

---

Primary Outcomes

Description: Size of collected audio dataset measured as number of collected cough sounds, targeting ≥10,000 identified coughs.

Measure: Dataset size

Time: 14 days

---

Secondary Outcomes

Description: Identification of cough sounds by the existing mathematical model with ≥ 99% specificity and ≥ 60% sensitivity

Measure: Cough sound identification

Time: 14 days

---

Description: 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 days

---

Description: 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 days

---

Primary Outcomes

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 months

---

Secondary Outcomes

Description: 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 months

---

Primary Outcomes

Measure: Time to improvement on a 7-point ordinal scale as compared to baseline

Time: 14 days or discharge

---

Secondary Outcomes

Measure: Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6)

Time: 14 days or discharge

---

Measure: Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples

Time: 14 days or discharge

---

Measure: In-hospital mortality

Time: 14 days or discharge

---

Measure: Mean change in NEWS2 score from baseline

Time: 14 days or discharge

---

Measure: Understand the effect of genetics for treatment response through whole genome sequence of the participant and the COVID-19 virus

Time: 14 days or discharge

---

Measure: Reduction from baseline of NRS for cough

Time: 14 days or discharge

---

Measure: Reduction from baseline of NRS for nausea

Time: 14 days or discharge

---

Measure: Time to normalization of fever for at least 48 hours

Time: 14 days or discharge

---

Measure: Time to improvement in oxygenation for at least 48 hours

Time: 14 days or discharge

---

Primary Outcomes

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 treatment

---

Secondary Outcomes

Measure: Respiratory rate

Time: Change from Baseline clinical measurements at 15 minutes post treatment

---

Measure: Heart rate

Time: Change from Baseline clinical measurements at 15 minutes post treatment

---

Measure: Blood pressure

Time: Change from Baseline clinical measurements at 15 minutes post treatment

---

Description: 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 treatment

---

Primary Outcomes

Measure: Correlation between nasal and deep PCR positivity for Covid-19 patients performed and all predictors for Covid-19 patients performed within 24 hours of admission to ICU

Time: within 24 hours of admission to ICU

---

Secondary Outcomes

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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 admission

---

Description: 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 days

---

Measure: Number of days on vasopressive amines

Time: during ICU stay, up to 28 days

---

Measure: Occurrence of an event of venous or arterial thromboembolic disease

Time: during ICU stay, up to 28 days

---

Measure: Number of days with extra renal treatment (ERA)

Time: during ICU stay, up to 28 days

---

Measure: Number of patients alive after ICU stay less than 28 days will be tracked

Time: At 28 day

---

Description: 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 stay

---

Description: 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 stay

---

Description: 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 stay

---

Description: 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 stay

---

Description: 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 stay

---

Measure: Correlation between number of patient deaths and all predictors for Covid-19 including anamnestic, clinical, biological, radiological parameters

Time: until day 28 after admission of ICU

---

Description: Evolution of viral clearance in nasal and depp PCR during ICU

Measure: Viral clearance

Time: through study completion, an average of 28 days

---

Primary Outcomes

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 years

---

Secondary Outcomes

Description: 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 years

---

Description: 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 years

---

Primary Outcomes

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 months

---

Secondary Outcomes

Description: 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 months

---

Description: Number of treatment discontinuations in each arm

Measure: Evaluation of the discontinuation rates of the investigational drug in each arm,

Time: Up to 2 months

---

Description: 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 months

---

Description: 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 months

---

Description: 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 months

---

Description: 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 months

---

Description: Safety. Electrocardiogram (ECG)

Measure: corrected QT interval (ms)

Time: At baseline, at D2 (only for COVIDAXIS 1) and every week up to 2 months.

---

Primary Outcomes

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 randomization

---

Secondary Outcomes

Description: The time since randomization to discharge between study groups

Measure: Lengh of hospital stay

Time: Up to 56 days post randomization

---

Description: The number of ventilator free days over the first 28 days of treatment

Measure: Ventilator free days

Time: first 28 days

---

Description: The number of oxygene free days over the first 28 days of treatment

Measure: Oxygene free days

Time: first 28 days

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: Time since randomization to the first defervescence day

Measure: fever clearance time

Time: Up to 56 days post randomization

---

Description: WHO Ordinal outcome scale for COVID-19

Measure: Ordinal outcome scale

Time: Up to 56 days post randomization

---

Description: Development of ARDS defined by the Kigali criteria

Measure: Development of ARDS

Time: Up to 56 days post randomization

---

Primary Outcomes

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 enrolment

---

Description: 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 enrolment

---

Secondary Outcomes

Description: 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 therapy

---

Description: PCR-confirmed COVID-19 diagnosis

Measure: Incidence rates of COVID-19 through study completion

Time: 28 days from enrolment

---

Primary Outcomes

Measure: Time to clinical improvement from day 0 to day 28 (improvement of two points on a seven-category ordinal scale, or live discharge from the hospital, whichever comes first)

Time: from day 0 to day 28 or hospital discharge

---

Secondary Outcomes

Measure: Primary safety endpoint: major adverse cardiac events defined as the composite of cardiovascular death, myocardial infarction, stroke or acute heart failure at day 28

Time: at day 28

---

Measure: Clinical status as assessed with the seven-category ordinal scale on days 7, 14 and 28.

Time: at days 7, 14 and 28

---

Measure: Number of days alive free of oxygen.

Time: from day 0 to day 28 or hospital discharge

---

Measure: Number of days alive outside hospital until day28

Time: at day28

---

Measure: Number of days alive free of intensive-care unit (ICU) admission or mechanical ventilation (invasive or non-invasive) until day28

Time: at day28

---

Measure: Number of days alive free of mechanical ventilation (invasive or non-invasive) until day28

Time: at day28

---

Measure: Number of days alive free of ICU admission until day28

Time: at day28

---

Measure: Rate of all-cause mortality at day 28

Time: at day 28

---

Measure: Rate of cardiovascular death at day 28

Time: at day 28

---

Measure: Number of days alive free of acute kidney injury until hospital discharge

Time: at day 28 to hospital discharge

---

Primary Outcomes

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 27

---

Description: percentage of cases of COVID 19

Measure: Prevalence of COVID-19 cases in both arms

Time: 27 weeks after the beginning of the study

---

Description: 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 study

---

Description: 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 study

---

Secondary Outcomes

Description: Presence and type of adverse events at this point.

Measure: Adverse events

Time: 12 weeks after the start of treatment

---

Description: Proportion of participants that drop out of study

Measure: Adverse events

Time: 27 weeks after the beginning of the study

---

Primary Outcomes

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 days

---

Secondary Outcomes

Measure: Mortality rate at D30

Time: At day30

---

Measure: Time (in days) from randomization to death

Time: up to 30 days after randomization

---

Measure: Number of days alive outside ICU within 30 days

Time: At day30

---

Measure: Number of days alive free of invasive or non-invasive ventilation within 30 days

Time: At day30

---

Measure: Number of days alive with oxygen therapy within 30 days

Time: At day30

---

Measure: Maximal oxygen rate within 30 days

Time: At day30

---

Measure: Difference between PaO2/FiO2 ratio at randomization and at Day 7 (or at the time of stopping oxygen therapy or discharge if occurs before Day 7)

Time: at Day 7

---

Measure: Number of days alive outside hospital within 30 days

Time: at Day 30

---

Measure: Use of antibiotics for respiratory (proved or suspected) infection within 30 days

Time: at Day 30

---

Measure: Difference between CRP levels at randomization and at Day 7 (or at the time of discharge if occurs before Day 7)

Time: at Day 7

---

Measure: Safety outcomes included events that occurred during treatment, serious adverse events, and premature discontinuation of treatment.

Time: up to 30 days after randomization

---

Primary Outcomes

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 90

---

Primary Outcomes

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 15

---

Secondary Outcomes

Description: 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 15

---

Description: 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 29

---

Description: 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 3

---

Description: 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 8

---

Description: 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 29

---

Description: 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 28

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: The number of days spent out of the ICU to day 28.

Measure: ICU-free days to Day 28

Time: 28 days after randomization

---

Description: 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 randomization

---

Other Outcomes

Description: 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 randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Description: 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 randomization

---

Primary Outcomes

Description: Rate of COVID-19 positive conversion on weekly nasopharyngeal (NP) sampling

Measure: Rate of COVID-19 positive conversion

Time: 7 weeks

---

Secondary Outcomes

Description: 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 weeks

---

Other Outcomes

Description: 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 weeks

---

Primary Outcomes

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 days

---

Secondary Outcomes

Description: To compare the infection rate of hospitalized patients versus healthcare workers

Measure: Fraction of healthcare workers with COVID-19

Time: 90 days

---

Description: Tracing origins of infection in healthcare workers to distinguish between community versus hospital acquired.

Measure: Number of patients infected in the hospital

Time: 90 days

---

Description: 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 months

---

Primary Outcomes

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 randomization

---

Secondary Outcomes

Description: 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 randomization

---

Description: 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 28

---

Description: 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 28

---

Description: 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)

---

Measure: Rate of throat swab negativation

Time: Day 7, Day 14, Day 28

---

Measure: Quantitative SARS-CoV-2 virus in throat swab and blood samples

Time: Day 7, Day 14, Day 28

---

Measure: Rate of secondary infection by other documented pathogens

Time: Day 7, Day 14, Day 28 (if available)

---

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)

---

Primary Outcomes

Measure: Number of confirmed symptomatic infections of SARS-CoV-2 (COVID-19)

Time: 12 weeks

---

Secondary Outcomes

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 weeks

---

Measure: Duration of symptoms in confirmed infected participants of SARS-CoV-2 (COVID-19) measured in days

Time: 12 weeks

---

Primary Outcomes

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 weeks

---

Description: 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 weeks

---

Primary Outcomes

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 14

---

Secondary Outcomes

Measure: Rates of death during the index hospitalization

Time: Index hospitalization, up to 46 days

---

Measure: Number of days on mechanical ventilation for patients who were on mechanical ventilation at baseline

Time: Baseline

---

Measure: Proportion of patients not receiving mechanical ventilation at baseline who progress to requiring mechanical ventilation during the index hospitalization

Time: Index hospitalization, up to 46 days

---

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: WHO ordinal scale measured at 28 days after enrollment

Time: Day 28

---

Measure: Hospital length of stay in days for the index hospitalization

Time: Index hospitalization, up to 46 days

---

Measure: Rates of all-cause study medication discontinuation

Time: Index hospitalization, up to 46 days

---

Measure: Rates of severe adverse events

Time: Day 14

---

Primary Outcomes

Description: Reduction in COVID-19 infection frequency

Measure: Reduction in COVID-19 infection frequency

Time: 30 days

---

Secondary Outcomes

Description: Number of participants testing positive in antibody screening at study start and study end, respectively

Measure: Antibody-screening

Time: 30 days

---

Primary Outcomes

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 days

---

Description: 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 days

---

Secondary Outcomes

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---

Description: 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 days

---