Correlated Drug Terms (156)

---

	Name (Synonyms)	Correlation
drug360	Hydroxychloroquine Wiki	0.20
drug616	Placebo Wiki	0.18
drug650	Presatovir Wiki	0.16
drug1008	pregnant women with laboratory-confirmed 2019-n-CoV Wiki	0.15
drug304	Favipiravir Wiki	0.13
drug361	Hydroxychloroquine (HCQ) Wiki	0.13
drug60	Ascorbic Acid Wiki	0.13
drug46	Anakinra Wiki	0.12
drug627	Placebo oral tablet Wiki	0.12
drug93	BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki	0.11
drug166	CYNK-001 Wiki	0.11
drug700	Risk of MERS infection Wiki	0.11
drug667	Quality of Life Wiki	0.11
drug188	Chest computed tomography (CT) Wiki	0.11
drug836	Thalidomide Wiki	0.11
drug806	Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors Wiki	0.11
drug679	Random Donor Plasma Wiki	0.11
drug800	Supportive Care Wiki	0.11
drug1037	trimethoprim/sulfamethoxazole Wiki	0.11
drug858	Toraymyxin PMX-20R (PMX Cartridge) Wiki	0.11
drug976	mRNA-1273 Wiki	0.11
drug149	COVID-19 IgM/IgG Rapid Testing, mobile device image capture and telemedicine support Wiki	0.11
drug326	Group A HCQ Wiki	0.11
drug62	Ascorbic Acid and Zinc Gluconate Wiki	0.11
drug493	Matched Placebo Wiki	0.11
drug448	Ivermectin plus Nitazoxanide Wiki	0.11
drug704	RoActemra iv Wiki	0.11
drug770	Standard medical care Wiki	0.11
drug604	Peginterferon Lambda-1a Wiki	0.11
drug684	Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki	0.11
drug57	Apo-Hydroxychloroquine Wiki	0.11
drug845	Thrombin Generation Assay (TGA) Wiki	0.11
drug590	PD-1 blocking antibody+standard treatment Wiki	0.11
drug351	Hospital anxiety and depression scale Wiki	0.11
drug763	Standard Donor Plasma Wiki	0.11
drug841	There is no intervention in this study Wiki	0.11
drug79	Awake Proning Wiki	0.11
drug847	Thrombomodulin Modified Thrombin Generation Assay (TGA-TM) Wiki	0.11
drug140	Burnout Wiki	0.11
drug910	XPro1595 Wiki	0.11
drug705	RoActemra sc Wiki	0.11
drug1029	standard treatment Wiki	0.11
drug1013	rapid salivary test Wiki	0.11
drug915	Zinc Wiki	0.11
drug154	COVID-19 convalescent plasma Wiki	0.11
drug373	Hydroxychloroquine Pre-Exposure Prophylaxis Wiki	0.11
drug227	Convalescent Plasma Transfusion Wiki	0.11
drug956	high flow nasal cannula (HFNC) Wiki	0.11
drug419	Indomethacin Wiki	0.11
drug318	GO2 PEEP MOUTHPIECE Wiki	0.11
drug916	Zinc Gluconate Wiki	0.11
drug80	Ayurveda Wiki	0.11
drug85	Azithromycin 500 milligram (mg) oral Tablet Wiki	0.11
drug581	Oral placebo Wiki	0.11
drug416	Impact Event Score Wiki	0.11
drug70	Association of diltiazem and niclosamide Wiki	0.11
drug918	Zithromax Oral Product Wiki	0.11
drug677	Radiological Detection Wiki	0.11
drug327	Group B Control Wiki	0.11
drug285	Enoxaparin Prefilled Syringe [Lovenox] Wiki	0.11
drug926	artus Influenza A/B RT-PCR Test Wiki	0.11
drug928	bacTRL-Spike Wiki	0.11
drug412	Imatinib Wiki	0.11
drug158	COVID-19 test, polymerase chain reaction for SARS-CoV-2 Wiki	0.11
drug985	muscle ultrasound Wiki	0.11
drug250	Data collection and rhinopharyngeal swab Wiki	0.11
drug830	Telmisartan arm will receive 80 mg Telmisartan twice daily plus standard care. Wiki	0.11
drug657	Prone positioning (PP) Wiki	0.11
drug971	laboratory biomarkers Wiki	0.11
drug168	Cambridge Validated Viral Detection Method Wiki	0.11
drug377	Hydroxychloroquine Sulfate + Azithromycin Wiki	0.11
drug651	Presatovir placebo Wiki	0.11
drug959	hospitalized children with Covid19 Wiki	0.11
drug804	Survey and Questionnaire Wiki	0.11
drug426	Injective placebo Wiki	0.11
drug852	To assess for development of IgG antibodies against SARS-CoV2 Wiki	0.11
drug122	Biological: COVID-19 convalescent plasma Wiki	0.11
drug902	Vitamins Wiki	0.11
drug252	Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days Wiki	0.11
drug454	Kevzara sc Wiki	0.11
drug835	Tetrandrine Wiki	0.11
drug450	JNJ-53718678 Wiki	0.11
drug422	Inhaled beclomethasone Wiki	0.11
drug468	Loop mediated isothermal amplification COVID-19 Wiki	0.11
drug352	Huaier Granule Wiki	0.11
drug676	REGN3051 Wiki	0.11
drug931	biological samples collection Wiki	0.11
drug849	Thymosin+standard treatment Wiki	0.11
drug733	Sarilumab SAR153191 Wiki	0.11
drug675	REGN3048 Wiki	0.11
drug237	Covid-19 Antibody testing (IgG and IgM) Wiki	0.11
drug744	Serum test Wiki	0.11
drug619	Placebo 250 cc 24 hours continuous infusion for 15 days Wiki	0.11
drug741	Serological test Wiki	0.11
drug680	Rapid diagnostics using Anyplex TMII RV16 Detection Wiki	0.11
drug987	nasopharyngeal swab Wiki	0.11
drug240	Cytokine profile Wiki	0.11
drug229	Convalescent anti-SARS-CoV-2 plasma Wiki	0.11
drug696	Retrospective data collection Wiki	0.11
drug37	Allogeneic NK transfer Wiki	0.11
drug532	NO intervention planned due to the observational study design only a diagnostic testing Wiki	0.11
drug776	Standard of care (SOC) Wiki	0.11
drug596	PTSD Wiki	0.11
drug598	Pacebo: Calcium citrate Wiki	0.11
drug290	Ergoferon Wiki	0.11
drug242	DAS181 Wiki	0.11
drug697	Reverse-transcription polymerase chain reaction (RT-PCR) Wiki	0.11
drug22	ACE inhibitor, angiotensin receptor blocker Wiki	0.11
drug339	Halo Oral Spray Wiki	0.11
drug342	Helmet non-invasive ventilation (NIV) Wiki	0.11
drug712	SAMBA II (Diagnostic for the Real World) Wiki	0.11
drug661	Public Health England Gold Standard Wiki	0.11
drug376	Hydroxychloroquine Sulfate (HCQ) Wiki	0.11
drug553	Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki	0.11
drug993	nosocomial infection/hospital acquired infection Wiki	0.11
drug727	Saline containing 1% Human serum albumin（solution of MSC） Wiki	0.11
drug340	Halo Placebo Wiki	0.11
drug379	Hydroxychloroquine Sulfate 200 MG Wiki	0.11
drug333	HCQ & AZ Wiki	0.11
drug254	Delayed diagnostics Anyplex TMII RV16 Detection Wiki	0.11
drug375	Hydroxychloroquine Sulfate Wiki	0.10
drug691	Remdesivir Wiki	0.10
drug208	Colchicine Wiki	0.10
drug900	Vitamin C Wiki	0.10
drug732	Sarilumab Wiki	0.09
drug671	Questionnaires Wiki	0.08
drug533	NORS (Nitric Oxide Releasing Solution) Wiki	0.08
drug107	Baricitinib Wiki	0.08
drug946	convalescent plasma Wiki	0.08
drug828	Telmisartan Wiki	0.08
drug995	observational Wiki	0.08
drug762	Standard Care Wiki	0.08
drug558	No intervention Wiki	0.08
drug486	MSCs Wiki	0.08
drug1018	self-administered questionnaire Wiki	0.08
drug130	Blood draw Wiki	0.08
drug771	Standard of Care Wiki	0.07
drug925	anti-SARS-CoV-2 convalescent plasma Wiki	0.06
drug92	BCG Vaccine Wiki	0.06
drug901	Vitamin D Wiki	0.06
drug823	Telemedicine Wiki	0.06
drug788	Standard treatment Wiki	0.06
drug169	Camostat Mesilate Wiki	0.06
drug429	Interferon Beta-1B Wiki	0.06
drug428	Interferon Beta-1A Wiki	0.06
drug632	Placebos Wiki	0.06
drug230	Convalescent plasma Wiki	0.05
drug854	Tocilizumab Wiki	0.05
drug883	Usual Care Wiki	0.05
drug668	Questionnaire Wiki	0.05
drug480	Losartan Wiki	0.04
drug1003	placebo Wiki	0.04
drug225	Convalescent Plasma Wiki	0.04
drug775	Standard of care Wiki	0.04
drug478	Lopinavir/ritonavir Wiki	0.03
drug82	Azithromycin Wiki	0.02

Correlated MeSH Terms (45)

---

	Name (Synonyms)	Correlation
D045169	Severe Acute Respiratory Syndrome NIH	0.41
D018352	Coronavirus Infections NIH	0.35
D007239	Infection NIH	0.32
D003141	Communicable Diseases NIH	0.31
D018357	Respiratory Syncytial Virus Infections NIH	0.22
D003333	Coronaviridae Infections NIH	0.19
D012327	RNA Virus Infections NIH	0.15
D005335	Fever of Unknown Origin NIH	0.11
D003384	Coxsackievirus Infections NIH	0.11
D012772	Shock, Septic NIH	0.11
D007154	Immune System Diseases NIH	0.11
D019446	Endotoxemia NIH	0.11
D040921	Stress Disorders, Traumatic NIH	0.11
D018805	Sepsis NIH	0.11
D000208	Acute Disease NIH	0.11
D002637	Chest Pain NIH	0.11
D055501	Macrophage Activation Syndrome NIH	0.11
D009220	Myositis NIH	0.11
D001987	Bronchiectasis NIH	0.11
D009205	Myocarditis NIH	0.11
D012141	Respiratory Tract Infections NIH	0.08
D016638	Critical Illness NIH	0.08
D012140	Respiratory Tract Diseases NIH	0.08
D007251	Influenza, Human NIH	0.08
D030341	Nidovirales Infections NIH	0.08
D058070	Asymptomatic Diseases NIH	0.08
D004630	Emergencies NIH	0.08
D013313	Stress Disorders, Post-Traumatic NIH	0.08
D000257	Adenoviridae Infections NIH	0.08
D004211	Disseminated Intravascular Coagulation NIH	0.06
D004417	Dyspnea NIH	0.06
D018184	Paramyxoviridae Infections NIH	0.06
D020246	Venous Thrombosis NIH	0.06
D011024	Pneumonia, Viral NIH	0.06
D011014	Pneumonia NIH	0.06
D012769	Shock, NIH	0.05
D020141	Hemostatic Disorders NIH	0.05
D001778	Blood Coagulation Disorders NIH	0.05
D008171	Lung Diseases, NIH	0.05
D058186	Acute Kidney Injury NIH	0.05
D013927	Thrombosis NIH	0.04
D055371	Acute Lung Injury NIH	0.03
D013577	Syndrome NIH	0.03
D012127	Respiratory Distress Syndrome, Newborn NIH	0.03
D012128	Respiratory Distress Syndrome, Adult NIH	0.03

Correlated HPO Terms (4)

---

	Name (Synonyms)	Correlation
HP:0002110	Bronchiectasis HPO	0.11
HP:0100749	Chest pain HPO	0.11
HP:0002098	Respiratory distress HPO	0.08
HP:0002090	Pneumonia HPO	0.02

Primary Outcomes

Measure: Death

Time: 60-day period following enrollment

---

Secondary Outcomes

Measure: Recovery from influenza illness (including days lost from normal activities) duration of hospitalization, days in intensive care, days of mechanical ventilation, days of dialysis, pregnancy outcome

Time: approximately 60 days

---

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: Number of participants with upper and lower respiratory tract infection will be detected and etiology of viral infection will be identified

Measure: Number of viral respiratory tract infection in participants according to etiology

Time: 6 months

---

Secondary Outcomes

Description: Serum concentration of vitamine D will be measured retrospectively from the blood samples taken at the beginning of the study and correlation between vitamine D concentration and the frequency of respiratory tract infection in participants will be made

Measure: Serum vitamine D concentration in participants

Time: 6 months

---

Description: Daily number of visitors in each nursing home room will be counted and correlate with the number of respiratory tract infection in participants.

Measure: Daily number of visitors in nursing home in correlation with the number of respiratory tract infection in residents

Time: 6 months

---

Primary Outcomes

Description: Respiratory viruses in the nasal swab and sputum will be identified using the polymerase chain reaction(PCR)technique when clinically stable and during exacerbation.The following viruses will be tested for:influenza A,B(including influenza A H1N1),respiratory syncytial virus(RSV),Enterovirus,Parainfluenza 1-4,Rhinovirus,human Coronaviruses(subtypes OC43、229E、HKU1),human metapneumovirus,adenovirus, human bocavirus,chlamydia,mycoplasma.

Measure: The prevalence of respiratory virus infection in adults with bronchiectasis during a pulmonary exacerbation and when clinically stable.

Time: 1 year

---

Secondary Outcomes

Description: Systemic and airway inflammatory cytokines including IL-1β、IL-6、IL-8、TNF-a were measured using a commercial multiplex bead-based assay.

Measure: The effect of respiratory virus infection on systemic and pulmonary inflammatory markers.

Time: 1 year

---

Description: Spirometric indices in the present study is referred to as forced expiratory vilume in 1s(FEV1),forced vital capacity(FVC).Spirometry tests are carried out using a spirometer (COSMED, QUARK PFT, Italy). All operation procedures meet the joint recommendation by ATS and ERS. A total of at least 3 (not more than 8) spirometric maneuvers are performed, with the variation between the best two maneuvers of <5% or 200ml in FVC and FEV1. The maximal values of FVC and FEV1 are reported.

Measure: The effect of respiratory virus on lung function

Time: 1 year

---

Description: Type of bacterial infection, also referred to as potentially pathogenic organisms, and bacterial load, as expressed in cfu per mililiter

Measure: The effect of respiratory virus infection on the bacterial load in bronchiectasis.

Time: 1 year

---

Description: The time from exacerbation onset by which a 3-d moving average was equal to or exceeded the baseline value

Measure: Time to recovery of respective symptom

Time: 1 year

---

Description: Quality of life in patients with bronchiectasis were measured by St.George Respiratory Questionnaire、Leicester Cough Questionnaire and COPD assessment test during exacerbations,and then compared between virus-postive and virus-negative patients

Measure: The effect of respiratory virus on quality of life in patients with bronchiectasis

Time: 1 year

---

Measure: To investigate if upper respiratory tract symptoms are associated with viral infections.

Time: 1 year

---

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 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: Time-Weighted Average Change in Viral Load From Day 1/Baseline Through Day 7 in Participants in the Full Analysis Set

Time: Up to 7 days

---

Measure: Time-Weighted Average Change in Viral Load From Day 1/Baseline Through Day 7 in a Subset of Participants in the Full Analysis Set Whose Duration of RSV Symptoms Prior to the First Dose of Study Drug is ≤ Median

Time: Up to 7 days

---

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) for the 5-point severity scale and 0 (never) to 4 or more times (always) for the 5-point frequency scale. 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 FLU-PRO Score From Day 1/Baseline Through Day 7

Time: Up to 7 days

---

Description: FEV1 is defined as forced expiratory volume in the first second.

Measure: Percent Change From Study Baseline in FEV1% Predicted Value

Time: Baseline; Day 28

---

Primary Outcomes

Description: The number of days in hospital within one month after randomization

Measure: Duration of hospitalization

Time: One month

---

Description: Number of days on antimicrobials within one month after randomization

Measure: Antimicrobial consumption

Time: One month

---

Description: Defined daily doses of antimicrobial agents within one month after randomization

Measure: Antimicrobial consumption

Time: One month

---

Secondary Outcomes

Measure: Number of radiological examinations

Time: One month

---

Measure: Cost of other examinations in hospital

Time: One month

---

Primary Outcomes

Measure: Numbers of infected patient

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

---

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

Measure: Changes from baseline in abbreviated physical examination

Time: Days 1-2

---

Measure: Changes from baseline in clinical safety laboratory values

Time: From Day 2 up to Day 121

---

Measure: Changes from baseline in Electrocardiogram (ECG) parameters

Time: 15 mins after infusion

---

Measure: Changes from baseline in Electrocardiogram (ECG) parameters

Time: 24 hrs after infusion

---

Measure: Changes from baseline in symptom-directed physical examination

Time: From Day 1 up to Day 121

---

Measure: Changes from baseline in vital signs

Time: From Day 1 up to Day 121

---

Measure: The incidence of Adverse Events

Time: From Day 1 up to Day 121

---

Measure: The incidence of treatment-emergent Serious Adverse Events

Time: From Day 1 up to Day 121

---

Measure: The severity of Adverse Events assessed by toxicity grading criteria

Time: From Day 1 up to Day 121

---

Measure: The severity of treatment-emergent Serious Adverse Events assessed by toxicity grading criteria

Time: From Day 1 up to Day 121

---

Measure: The type of treatment-emergent Serious Adverse Events

Time: From Day 1 up to Day 121

---

Secondary Outcomes

Measure: AUC for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: AUC for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: AUC(0-infinity) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: AUC(0-infinity) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: CL for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: CL for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: CMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: CMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: K(e) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: K(e) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: t(1/2) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: t(1/2) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: The change from baseline of antibodies against REGN3048 and REGN3051 (anti-drug antibodies, ADA), as measured in serum using validated bridging assays

Time: Day 121

---

Measure: The change from baseline of antibodies against REGN3048 and REGN3051 (anti-drug antibodies, ADA), as measured in serum using validated bridging assays

Time: Day 57

---

Measure: TMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: TMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: V(ss) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

Measure: V(ss) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

---

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: 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: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.

Measure: Time to recovery

Time: Day 1 through Day 29

---

Secondary Outcomes

Measure: Change from baseline in alanine transaminase (ALT)

Time: Day 1 through Day 29

---

Measure: Change from baseline in aspartate transaminase (AST)

Time: Day 1 through Day 29

---

Measure: Change from baseline in creatinine

Time: Day 1 through Day 29

---

Measure: Change from baseline in glucose

Time: Day 1 through Day 29

---

Measure: Change from baseline in hemoglobin

Time: Day 1 through Day 29

---

Measure: Change from baseline in platelets

Time: Day 1 through Day 29

---

Measure: Change from baseline in prothrombin time (PT)

Time: Day 1 through Day 29

---

Measure: Change from baseline in total bilirubin

Time: Day 1 through Day 29

---

Measure: Change from baseline in white blood cell count (WBC) with differential

Time: Day 1 through Day 29

---

Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

Measure: Change in National Early Warning Score (NEWS) from baseline

Time: Day 1 through Day 29

---

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: Clinical status using ordinal scale

Time: Day 3 through Day 29

---

Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.

Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

Time: Day 1 through Day 29

---

Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

Measure: Cumulative incidence of serious adverse events (SAEs)

Time: Day 1 through Day 29

---

Description: For any reason.

Measure: Discontinuation or temporary suspension of investigational therapeutics

Time: Day 1 through Day 10

---

Description: Measured in days.

Measure: Duration of hospitalization

Time: Day 1 through Day 29

---

Description: Measured in days.

Measure: Duration of new non-invasive ventilation or high flow oxygen use

Time: Day 1 through Day 29

---

Description: Measured in days.

Measure: Duration of new oxygen use

Time: Day 1 through Day 29

---

Description: Measured in days.

Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

Time: Day 1 through Day 29

---

Measure: Incidence of new non-invasive ventilation or high flow oxygen use

Time: Day 1 through Day 29

---

Measure: Incidence of new oxygen use

Time: Day 1 through Day 29

---

Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

Time: Day 1 through Day 29

---

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: Mean change in the ordinal scale

Time: Day 1 through Day 29

---

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: Percentage of subjects reporting each severity rating on an 8-point ordinal scale

Time: Day 15

---

Description: Date and cause of death (if applicable).

Measure: Subject 14-day mortality

Time: Day 1 through Day 15

---

Description: Date and cause of death (if applicable).

Measure: Subject 29-day mortality

Time: Day 1 through Day 29

---

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: Time to an improvement of one category using an ordinal scale

Time: Day 1 through Day 29

---

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: Time to an improvement of two categories using an ordinal scale

Time: Day 1 through Day 29

---

Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

Measure: Time to discharge or to a National Early Warning Score (NEWS) of Time: Day 1 through Day 29

---

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: Evaluation of Pneumonia Improvement

Measure: Size of lesion area and severity of pulmonary fibrosis by chest CT

Time: At Baseline , Day 6, Day 10, Day 14, Day 28 and Day 90

---

Secondary Outcomes

Description: Evaluation of Pneumonia Improvement No limitation of activities, discharged from hospital =Score 1; Hospitalized, no oxygen therapy=Score 2; Oxygen by mask or nasal prongs-Score 3; Non-invasive ventilation or high-flow oxygen=Score 4; Mechanical ventilation or ECMO=Score 5; Death=Score 6.

Measure: mMRC (Modified Medical Research Council) dyspnea scale

Time: Baseline , Day 7, Day 14, Day 28, Day 90

---

Description: Evaluation of Pneumonia Improvement

Measure: Oxygenation index( PaO2/FiO2)

Time: Baseline , Day 7, Day 14, Day 28, Day 90

---

Description: Evaluation of Pneumonia Improvement

Measure: Duration of oxygen therapy(days)

Time: Day 28, Day 90

---

Description: Evaluation of Pneumonia Improvement

Measure: Duration of hospitalization(days)

Time: Day 28, Day 90

---

Description: Evaluation of Pneumonia Improvement

Measure: Blood oxygen saturation

Time: Baseline , Day 7, Day 14, Day 28, Day 90

---

Description: Marker of Immunological function

Measure: CD4+ T cell count and cytokine level

Time: Baseline , Day 6, Day 10, Day 14, Day 21, Day 28, Day 90

---

Description: Proportion of participants with treatment-related adverse events as assessed by CTCAE v4.0

Measure: Side effects in the MSCs treatment group

Time: Baseline , Day 3, Day 6，Day 10, Day 14, Day 21, Day 28, Day 90

---

Description: Evaluation of Pneumonia Improvement

Measure: 6-minute walk test

Time: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90

---

Description: Evaluation of Pneumonia Improvement

Measure: Maximum vital capacity (VCmax)

Time: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90

---

Description: Evaluation of Pneumonia Improvement

Measure: Diffusing Capacity (DLCO)

Time: Baseline, Day 10, Day 14, Day 21, Day 28, Day 90

---

Primary Outcomes

Description: The primary outcome criteria will be the proportion of patients, caregivers and health care professionals with confirmed or suspected SARS-CoV-2 nosocomial infection relative to all patients, caregivers and health care professionals with syndromes suggestive of SARS-CoV-2 infection during the study period. The infection control measures will be reported and describe according the nosocomial cases.

Measure: nosocomial infection

Time: At inclusion

---

Primary Outcomes

Description: Death event

Measure: Survival rate

Time: 12 weeks

---

Secondary Outcomes

Description: inflammatory indicator

Measure: body temperature

Time: 2 weeks

---

Primary Outcomes

Description: different maternal and perinatal outcomes were evaluated including: admission to ICU, use of mechanical ventilation, maternal death, early pregnany loss, perinatal death, intrauterine growth restriction (IUGR), preterm birth, mode of delivery, LBW, admission to neonatal ICU (NICU), and clinical or serologic evidence of vertical trasmission

Measure: Maternal and perinatal outcomes

Time: during gestation and at the time of delivery of the baby

---

Primary Outcomes

Description: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.

Measure: Percentage of subjects reporting each severity rating on a 7-point ordinal scale

Time: Day 15

---

Secondary Outcomes

Description: Time to an improvement of one category from admission on an ordinal scale. Subject clinical status on an ordinal scale at days 3, 5, 8, 11, and 29. Mean change in the ranking on an ordinal scale from baseline to days 3, 5, 8, 11, 15 and 29 from baseline.

Measure: Percentage of subjects reporting each severity rating on a 7-point on an ordinal scale

Time: Days 3, 5, 8, 11, 15 and 29

---

Description: • Change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS.

Measure: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first.

Time: Days 3, 5, 8, 11, 15 and 29

---

Measure: Number of oxygenation free days in the first 28 days

Time: 29 days

---

Measure: Incidence of new oxygen use, non-invasive ventilation or high flow oxygen devices during the trial.

Time: 29 days

---

Measure: Duration of new oxygen use, non-invasive ventilation or high flow oxygen devices during the trial.

Time: 29 days

---

Measure: Ventilator free days in the first 28 days

Time: 29 days

---

Measure: Incidence of new mechanical ventilation use during the trial.

Time: 29 days

---

Description: • Duration of hospitalization (days).

Measure: Hospitalization

Time: 29 days

---

Description: Rate of mortality

Measure: Mortality

Time: In hospital, Day 28, Day 90

---

Measure: Cumulative incidence of serious adverse events (SAEs)

Time: 29 days

---

Measure: Cumulative incidence of Grade 3 and 4 adverse events (AEs)

Time: 29 days

---

Measure: Number of participants with a discontinuation or temporary suspension of study drugs (for any reason)

Time: 29 days

---

Measure: Changes from baseline in blood white cell count

Time: 29 days

---

Measure: Changes from baseline in haemoglobin

Time: 29 days

---

Measure: Changes from baseline in platelets

Time: 29 days

---

Measure: Changes from baseline in creatinine

Time: 29 days

---

Measure: Changes from baseline in blood electrolytes (including kaliemia)

Time: 29 days

---

Measure: Changes from baseline in prothrombine time

Time: 29 days

---

Measure: Changes from baseline in international normalized ratio (INR)

Time: 29 days

---

Measure: Changes from baseline in glucose

Time: 29 days

---

Measure: Changes from baseline in total bilirubin

Time: 29 days

---

Measure: Changes from baseline in alanine aminotransferase (ALT)

Time: 29 days

---

Measure: Changes from baseline in aspartate aminotransferase (AST)

Time: 29 days

---

Other Outcomes

Measure: Percent of subjects with SARS-CoV-2 detectable in nasopharyngeal sample

Time: Days 3, 5, 8, 11, 15, 29

---

Measure: Quantitative SARS-CoV-2 virus in nasopharyngeal sample

Time: Days 3, 5, 8, 11, 15, 29

---

Measure: Quantitative SARS-CoV-2 virus in blood

Time: Days 3, 5, 8 and 11

---

Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized

Measure: Plasma concentration of lopinavir

Time: Days 1, 3, 5, 8 and 11

---

Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized

Measure: Plasma concentration of hydroxychloroquine

Time: Days 1, 3, 5, 8 and 11

---

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: This is defined as either 1. COVID-19 infection confirmed within 14 days of enrollment, following self-report of COVID-19 symptoms to the research study; OR, 2. COVID-19 infection confirmed within 14 days of enrollment, with self-report of COVID-19 symptoms to a treating physician.

Measure: Number of participants with symptomatic, lab-confirmed COVID-19.

Time: Date of enrollment to 14 days post-enrollment date

---

Primary Outcomes

Description: different maternal and perinatal outcomes were evaluated including: admission to ICU, use of mechanical ventilation, maternal death, early pregnany loss, perinatal death, intrauterine growth restriction (IUGR), preterm birth, mode of delivery, LBW, admission to neonatal ICU (NICU), and clinical or serologic evidence of vertical trasmission

Measure: Maternal and perinatal outcomes

Time: at the time of delivery

---

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

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: The primary endpoint will be the composite of death or the need for hospitalization due to COVID-19 infection in the first 30 days after randomization.

Measure: Number of participants who die or require hospitalization due to COVID-19 infection

Time: 30 days post randomization

---

Secondary Outcomes

Description: The secondary endpoint is the occurrence of death in the 30 days following randomization.

Measure: Number of participants who die

Time: 30 days post randomization

---

Description: The secondary endpoint is the need for hospitalization due to COVID-19 infection in the 30 days following randomization.

Measure: Number of participants requiring hospitalization due to COVID-19 infection

Time: 30 days post randomization

---

Description: The secondary endpoint is the need for mechanical ventilation in the 30 days following randomization.

Measure: Number of participants requiring mechanical ventilation

Time: 30 days post randomization

---

Primary Outcomes

Measure: Time to independence from supplementary oxygen therapy

Time: days from enrolment up 28 days

---

Secondary Outcomes

Measure: Number of deaths

Time: 28 days from enrolment

---

Measure: Days out of hospital and alive

Time: 28 days from enrolment

---

Measure: Ventilator free days alive and out of hospital

Time: 28 days from enrolment

---

Description: Measured from standard blood test

Measure: C-reactive protein (CRP) level

Time: baseline

---

Description: Measured from standard blood test

Measure: C-reactive protein (CRP) level

Time: peak during hospitalisation, up to 28 days

---

Description: Measured from standard blood test

Measure: C-reactive protein (CRP) level

Time: 14 days

---

Description: Measured from standard blood test

Measure: C-reactive protein (CRP) level

Time: 28 days

---

Description: Measured as occurrence of any serious adverse events

Measure: Number of participants with serious adverse events

Time: During treatment, up to 28 days

---

Primary Outcomes

Description: Primary outcome will be to measure ICU and hospital mortality up to 7 days of COVID-19 patients

Measure: ICU and hospital mortality of COVID-19 patients

Time: 7 days

---

Secondary Outcomes

Description: Secondary outcome will be to measure 30 days mortality from Hospital discharge

Measure: 30 days mortality

Time: 30 days

---

Primary Outcomes

Description: Overall Survival

Measure: Survival

Time: 14 days

---

Description: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10

Measure: WHO progression scale COVID 19

Time: 14 days

---

Primary Outcomes

Description: Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.

Measure: Survival without needs of ventilator utilization at day 14.

Time: 14 days

---

Description: Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10

Measure: WHO progression scale <=5 at day 4

Time: 4 days

---

Description: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.

Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14

Time: 14 days

---

Description: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event. Scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9

Measure: WHO progression scale at day 4

Time: 4 days

---

Secondary Outcomes

Description: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10

Measure: WHO progression scale

Time: 7 and 14 days

---

Description: Overall survival

Measure: Survival

Time: 14, 28 and 90 days

---

Measure: 28-day ventilator free-days

Time: 28 days

---

Description: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours

Measure: respiratory acidosis at day 4

Time: 4 days

---

Description: evolution of PaO2/FiO2 ratio

Measure: PaO2/FiO2 ratio

Time: day 1 to day 14

---

Description: time to oxygen supply independency

Measure: time to oxygen supply independency

Time: 14 days

---

Description: duration of hospitalization

Measure: duration of hospitalization

Time: 90 days

---

Description: time to negative viral excretion

Measure: time to negative viral excretion

Time: 90 days

---

Description: time to ICU discharge

Measure: time to ICU discharge

Time: 90 days

---

Description: time to hospital discharge

Measure: time to hospital discharge

Time: 90 days

---

Primary Outcomes

Description: the treatment failure rate of HFNC/HFNC+PP support and clinical requirement for advanced respiratory support

Measure: Treatment failure

Time: 28 days

---

Measure: Intubation rate

Time: 28 days

---

Secondary Outcomes

Description: the improvement of SpO2/FIO2 or PaO2/FiO2 from HFNC alone to HFNC+PP

Measure: Efficacy of PP

Time: 28 days

---

Primary Outcomes

Description: Measuring the diagnostic accuracy of the SAMBA II POC-sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) tested against a dual composite reference standard

Measure: SAMBA COVID-19 POC PCR Test

Time: 28 days

---

Secondary Outcomes

Description: Evaluating the participant acceptability of the SAMBA swab intervention using a participant reported discomfort scale

Measure: Patient acceptability

Time: 28 days

---

Description: Time to positive IgM/IgG test positivity

Measure: Immune Response Positivity

Time: 40 days

---

Primary Outcomes

Description: Time to increase in C-reactive protein to 3 times the ULN

Measure: CRP increase to 3 x upper limit of normal

Time: 3 weeks

---

Description: Time to clinical deterioration (2 levels in the WHO R&D Blueprint scale)

Measure: Clinical deterioration in the semiquantitative ordinal scale suggested by the WHO R&D committee

Time: 3 weeks

---

Description: Maximal concentration of high-sensitivity cardiac troponin

Measure: Maximal concentration of cardiac troponin

Time: 10 days

---

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: Number of participants with COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)

Measure: COVID-19 disease incidence

Time: Measured over the 6 months following randomisation

---

Description: Number of participants who were admitted to hospital or died (using self-reported questionnaire and/or medical/hospital records) in the context of a positive SARS-CoV-2 test

Measure: Severe COVID-19 disease incidence

Time: Measured over the 6 months following randomisation

---

Secondary Outcomes

Description: Number of participants with COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)

Measure: COVID-19 incidence by 12 months

Time: Measured over the 12 months following randomisation

---

Description: Number of participants with severe COVID-19 disease defined as hospitalisation or death in the context of a positive SARS-Cov-2 test (PCR or serology)

Measure: Severe COVID-19 incidence by 12 months

Time: Measured over the 12 months following randomisation

---

Description: Time to first symptom of COVID-19 in a participant who subsequently meets the case definition: fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)

Measure: Time to first symptom of COVID-19

Time: Measured over the 12 months following randomisation

---

Description: Number of episodes of COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)

Measure: Episodes of COVID-19

Time: Measured over the 12 months following randomisation

---

Description: Number of participants with asymptomatic SARS-CoV-2 infection defined as Evidence of SARS-CoV-2 infection (by PCR or seroconversion) Absence of respiratory illness (using self-reported questionnaire) No evidence of exposure prior to randomisation (inclusion serology negative)

Measure: Asymptomatic SARS-CoV-2 infection

Time: Measured over the 12 months following randomisation

---

Description: Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)

Measure: Work absenteeism due to COVID-19

Time: Measured over the 12 months following randomisation

---

Description: Number of days confined to bed (using self-reported questionnaire) due to COVID-19 disease defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)

Measure: Bed confinement due to COVID-19

Time: Measured over the 12 months following randomisation

---

Description: Number of days with symptoms in any episode of illness that meets the case definition for COVID-19 disease: fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire), plus positive SARS-Cov-2 test (PCR or serology)

Measure: Symptom duration of COVID-19

Time: Measured over the 12 months following randomisation

---

Description: Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test

Measure: SARS-CoV-2 pneumonia

Time: Measured over the 12 months following randomisation

---

Description: Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test

Measure: Oxygen therapy with SARS-CoV-2

Time: Measured over the 12 months following randomisation

---

Description: Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test

Measure: Critical care admissions with SARS-CoV-2

Time: Measured over the 12 months following randomisation

---

Description: Number of days admitted to critical care (using self-reported questionnaire and/or medical/hospital records) associated with a positive SARS-CoV-2 test

Measure: Critical care admission duration with SARS-CoV-2

Time: Measured over the 12 months following randomisation

---

Description: Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test

Measure: Mechanical ventilation with SARS-CoV-2

Time: Measured over the 12 months following randomisation

---

Description: Number of days that participants needed mechanical ventilation (using self-reported questionnaire and/or medical/hospital records) and a positive SARS-CoV-2 test

Measure: Mechanical ventilation duration with SARS-CoV-2

Time: Measured over the 12 months following randomisation

---

Description: Number of days of hospitalisation due to COVID-19 (using self-reported questionnaire and/or medical/hospital records).

Measure: Hospitalisation duration with COVID-19

Time: Measured over the 12 months following randomisation

---

Description: Number of deaths (from death registry) associated with a positive SARS-CoV-2 test

Measure: Mortality with SARS-CoV-2

Time: Measured over the 12 months following randomisation

---

Description: Number of participants with febrile respiratory illness defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)

Measure: Febrile respiratory illness

Time: Measured over the 12 months following randomisation

---

Description: Number of episodes of febrile respiratory illness, defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)

Measure: Episodes of febrile respiratory illness

Time: Measured over the 12 months following randomisation

---

Description: Number of days (using self-reported questionnaire) unable to work (excludes quarantine/workplace restrictions) due to febrile respiratory illness defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)

Measure: Work absenteeism due to febrile respiratory illness

Time: Measured over the 12 months following randomisation

---

Description: Number of days confined to bed (using self-reported questionnaire) due to febrile respiratory illness defined as fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)

Measure: Bed confinement due to febrile respiratory illness

Time: Measured over the 12 months following randomisation

---

Description: Number of days with symptoms in any episode of illness that meets the case definition for febrile respiratory illness: fever (using self-reported questionnaire), plus at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure, runny/blocked nose (using self-reported questionnaire)

Measure: Symptom duration of febrile respiratory illness

Time: Measured over the 12 months following randomisation

---

Description: Number of pneumonia cases (abnormal chest X-ray) (using self-reported questionnaire and/or medical/hospital records)

Measure: Pneumonia

Time: Measured over the 12 months following randomisation

---

Description: Need for oxygen therapy (using self-reported questionnaire and/or medical/hospital records)

Measure: Oxygen therapy

Time: Measured over the 12 months following randomisation

---

Description: Number of admission to critical care (using self-reported questionnaire and/or medical/hospital records)

Measure: Critical care admissions

Time: Measured over the 12 months following randomisation

---

Description: Number of participants needing mechanical ventilation (using self-reported questionnaire and/or medical/hospital records)

Measure: Mechanical ventilation

Time: Measured over the 12 months following randomisation

---

Description: Number of deaths (from death registry)

Measure: Mortality

Time: Measured over the 12 months following randomisation

---

Description: Number of days of hospitalisation due to febrile respiratory illness (using self-reported questionnaire and/or medical/hospital records)

Measure: Hospitalisation duration with febrile respiratory illness

Time: Measured over the 12 months following randomisation

---

Description: Number of days of unplanned absenteeism for any reason (using self-reported questionnaire)

Measure: Unplanned work absenteeism

Time: Measured over the 12 months following randomisation

---

Description: Cost of hospitalisation due to COVID-19 reported in Australian dollars (using hospital administrative linked costing records held by individual hospitals and state government routine costing data collections to provide an estimate of the cost to hospitals for each episode of COVID-19 care)

Measure: Hospitalisation cost to treat COVID-19

Time: Measured over the 12 months following randomisation

---

Description: Type and severity of local and systemic adverse events will be collected in self-reported questionnaire and graded using toxicity grading scale.

Measure: Local and systemic adverse events to BCG vaccination in healthcare workers

Time: Measured over the 3 months following randomisation

---

Primary Outcomes

Description: Resolution of fever is defined as body temperature: ≤36.6 C (axilla) or ≤37.2 C (oral), or ≤37.8 C (rectal or tympanic).

Measure: Phase 2: Time to resolution of fever for at least 48 hours without antipyretics or until discharge, whichever is sooner

Time: Baseline to Day 29

---

Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

Measure: Phase 3: The percentage of patients reporting each severity rating on the 7-point ordinal scale

Time: Baseline to Day 15

---

Secondary Outcomes

Description: Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.

Measure: Phase 2: The time to improvement in oxygenation

Time: Baseline to Day 29

---

Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

Measure: Phase 2: Mean change in 7-point ordinal scale from baseline to Day 15

Time: Baseline to Day 15

---

Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

Measure: Phase 2: Clinical status using the 7-point ordinal scale at Day 15

Time: Baseline to Day 15

---

Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

Measure: Phase 2: Time to improvement of two categories from admission using the 7-point ordinal scale

Time: Baseline to Day 29

---

Description: Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.

Measure: Phase 2 and 3 : Time to resolution of fever

Time: Baseline to Day 29

---

Description: Increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2) for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.

Measure: Phase 2 and 3 : Time to improvement in oxygenation

Time: Baseline to Day 29

---

Description: Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2) for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.

Measure: Phase 2 and 3: Time to resolution of fever and improvement in oxygenation

Time: Baseline to Day 29

---

Description: The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.

Measure: Phase 2 and 3:Time to change in NEWS2 from baseline

Time: Baseline to Day 29

---

Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.

Measure: Phase 2 and 3: Time to NEWS2 of <2 and maintained for 24 hours

Time: Baseline to Day 29

---

Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.

Measure: Phase 2 and 3: Mean change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS2

Time: Baseline to days 3, 5, 8, 11, 15, and 29

---

Description: Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24 period.

Measure: Phase 2 and 3:Days with fever

Time: Baseline to Day 29

---

Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.

Measure: Phase 2 and 3: Alive off supplemental oxygen at day 29

Time: Baseline to Day 29

---

Measure: Phase 2 and 3: Days of resting respiratory rate >24 breaths/min

Time: Baseline to Day 29

---

Description: Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.

Measure: Phase 2 and 3:Days of hypoxemia

Time: Baseline to Day 29

---

Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.

Measure: Phase 2 and 3: Days of supplemental oxygen use

Time: Baseline to Day 29

---

Measure: Phase 2 and 3: Time to saturation ≥94% on room air

Time: Baseline to Day 29

---

Measure: Phase 2 and 3: Ventilator free days in the first 28 days (to day 29)

Time: Baseline to Day 29

---

Description: For those not requiring these interventions at baseline.

Measure: Phase 2 and 3: The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula

Time: Baseline to Day 60

---

Measure: Phase 2 and 3: Proportion of patients requiring rescue medication during the 28-day period

Time: Baseline to Day 28

---

Description: For patients are not in ICU at baseline

Measure: Phase 2 and 3: The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available)

Time: Baseline to Day 60

---

Measure: Phase 2 and 3: Days of hospitalization among survivors

Time: Baseline to Day 60

---

Measure: Phase 2 and 3: Incidence of death

Time: Baseline to Day 60

---

Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

Measure: Phase 3: Mean change in the 7-point ordinal scale from baseline to days 3, 5, 8, 11, 15, and 29 (or until discharge)

Time: baseline to days 3, 5, 8, 11, 15, and 29 (or until discharge)

---

Description: The ordinal scale is an assessment of the clinical status. Scores range 1-7. Lower score is worse.

Measure: Phase 3: Clinical status using the 7-point ordinal scale at days 3, 5, 8, 11,15, and 29

Time: Days 3, 5, 8, 11,15, and 29

---

Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

Measure: Phase 3: Time to improvement of two categories from admission using the 7-point ordinal scale

Time: Baseline to Day 29

---

Measure: Phase 2 and 3: Incidence of serious adverse events

Time: Baseline to Day 60

---

Measure: Phase 2 and 3: The incidence of major or opportunistic bacterial or fungal infections

Time: Baseline to Day 60

---

Measure: Phase 2 and 3: The incidence of major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia

Time: Baseline to Day 60

---

Measure: Phase 2 and 3: The incidence of hypersensitivity reactions, infusion reactions, gastrointestinal perforation

Time: Baseline to Day 60

---

Measure: The number of patients with clinically significant laboratory abnormalities

Time: Baseline to Day 60

---

Primary Outcomes

Description: Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.

Measure: COVID-19-free survival

Time: up to 12 weeks

---

Secondary Outcomes

Description: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.

Measure: Incidence of confirmed SARS-CoV-2 detection

Time: up to 12 weeks

---

Description: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.

Measure: Incidence of possible COVID-19 symptoms

Time: up to 12 weeks

---

Description: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.

Measure: Incidence of all-cause study medicine discontinuation

Time: up to 12 weeks

---

Description: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.

Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end

Time: up to 12 weeks

---

Description: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.

Measure: Incidence of Hospitalization for COVID-19 or death

Time: up to 12 weeks

---

Description: Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.

Measure: Incidence of study medication-related side effects

Time: up to 12 weeks

---

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

Description: Group 1. Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.

Measure: Survival without needs of ventilator utilization at day 14. Group 1

Time: 14 days

---

Description: Group 1. Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10

Measure: WHO progression scale <=5 at day 4. Group 1.

Time: 4 days

---

Description: Group 2. Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.

Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14. Group 2.

Time: 14 days

---

Description: Group 2 Early end point : proportion of patients with a decrease of WHO score of at least 1 point at day 4. WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10

Measure: WHO progression scale at day 4. Group 2.

Time: 4 days

---

Secondary Outcomes

Description: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10

Measure: WHO progression scale

Time: 7 and 14 days

---

Description: Overall survival

Measure: Survival

Time: 14, 28 and 90 days

---

Measure: 28-day ventilator free-days

Time: 28 days

---

Description: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours

Measure: respiratory acidosis at day 4

Time: 4 days

---

Description: evolution of PaO2/FiO2 ratio

Measure: PaO2/FiO2 ratio

Time: day 1 to day 14

---

Description: time to oxygen supply independency

Measure: time to oxygen supply independency

Time: 14 days

---

Description: duration of hospitalization

Measure: duration of hospitalization

Time: 90 days

---

Description: time to negative viral excretion

Measure: time to negative viral excretion

Time: 90 days

---

Description: time to ICU discharge

Measure: time to ICU discharge

Time: 90 days

---

Description: time to hospital discharge

Measure: time to hospital discharge

Time: 90 days

---

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: This outcome will be assessed by comparing the percentages of enrolled patients that are hospitalized in the treatment and control arms.

Measure: Total Hospitalization

Time: 14 days

---

Description: This outcome will be assessed by comparing the percentages of enrolled patients that have received mechanical ventilation in the treatment and control arms.

Measure: Total Mechanical Ventilation

Time: 14 days

---

Secondary Outcomes

Description: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.

Measure: Fever intensity measure

Time: 2 days

---

Description: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.

Measure: Fever intensity measure

Time: 5 days

---

Description: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.

Measure: Fever intensity measure

Time: 10 days

---

Description: Self-reported body temperature. Each report scored low (less than 100.4), medium (100.4-102.2), or high (higher than 102.2). Outcome will be assessed by calculating percentage of patients with reported high, medium, low temperature at specified time points.

Measure: Fever intensity measure

Time: 14 days

---

Description: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.

Measure: Shortness of breath measure

Time: 2 days

---

Description: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.

Measure: Shortness of breath measure

Time: 5 days

---

Description: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.

Measure: Shortness of breath measure

Time: 10 days

---

Description: Self-reported worsening shortness of breath. Each report scored yes/no. Outcome will be assessed by calculating percentage of patients with reported worsening of shortness of breath at specified time points.

Measure: Shortness of breath measure

Time: 14 days

---

Description: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.

Measure: Changes in daytime cough measure

Time: 2 days

---

Description: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.

Measure: Changes in daytime cough measure

Time: 5 days

---

Description: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.

Measure: Changes in daytime cough measure

Time: 10 days

---

Description: Self reported changes in daytime cough. Each report scored 0 (no cough), 1 (one short coughing attack), 2 (two or more short coughing attacks), 3 (frequent coughing that did not interfere with activities), 4 (frequent coughing that did interfere with activities, 5 (distressing cough throughout most of the day). Outcome will be measured by calculating change in reported cough at each time point.

Measure: Changes in daytime cough measure

Time: 14 days

---

Description: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.

Measure: Changes in nighttime cough measure

Time: 2 days

---

Description: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.

Measure: Changes in nighttime cough measure

Time: 5 days

---

Description: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.

Measure: Changes in nighttime cough measure

Time: 10 days

---

Description: Self reported changes in nighttime cough. Each report scored 0 (no cough), 1 (cough on waking only), 2 (wake once or early due to cough), 3 (frequent waking due to cough), 4 (frequent coughing throughout the night, 5 (distressing cough preventing any sleep). Outcome will be measured by calculating change in reported cough at each time point.

Measure: Changes in nighttime cough measure

Time: 14 days

---

Description: Number of enrolled patients who have died within the specified time frame

Measure: Total mortality

Time: 28 days

---

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

Measure: Symptomatic or asymptomatic SARS-CoV-2 infection confirmed by PCR

Time: 4 weeks

---

Secondary Outcomes

Measure: Viral load during SARS-CoV-2 infection

Time: 4 weeks

---

Measure: Seroconversion during the study period

Time: 4 weeks

---

Measure: Incidence of any acute respiratory infection

Time: 4 weeks

---

Measure: Days of sick leave

Time: 4 weeks

---

Primary Outcomes

Measure: Prevalence of positivity of COVID-19 virus measured by rt-PCR

Time: At 28 days

---

Secondary Outcomes

Description: children admitted to pediatric emergencies for respiratory signs Children hospitalized as a result of travelling to pediatric emergency departments for respiratory signs Respiratory asymptomatic children admitted to pediatric emergencies

Measure: Prevalence of positivity of COVID-19 virus measured by rt-PCR in the following subpopulations of emergency patients

Time: at the end an average 28 days

---

Measure: Respiratory signs of children tested within 28 day

Time: through study completion, an average 28 days

---

Measure: Percentage of children hospitalized tested within 28 day

Time: through study completion, an average 28 days

---

Description: the degree of relationship with these contacts and the time spent in contact with them within 24 hours before emergency

Measure: Contact frequency

Time: At inclusion

---

Measure: Prevalence of positivity of other respiratory viruses measured by rt-PCR

Time: at 28 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

---

Primary Outcomes

Description: At least 25% decrease between baseline sequential organ failure assessment SOFA score and measured sequential organ failure assessment SOFA score at Study Day 8

Measure: Change of baseline total sequential organ failure assessment (SOFA) score

Time: Visit study day 8

---

Description: Resolution of all criteria of lower respiratory tract involvemed that led to study inclusion (except findings from imaging studies) at Study Day 8

Measure: Improvement of lung involvement measurements

Time: Visit study day 8

---

Description: At least 50% increase of pO2/FiO2 ratio between baseline and study visit Day 8

Measure: Increase of pO2/FiO2 ratio

Time: Visit Study Day 8

---

Secondary Outcomes

Description: Change of total sequential organ failure assessment (SOFA) score between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database (Sequential organ failure assessment range 0-24, high score associated with worst outcome)

Measure: Comparison of change of baseline total sequential organ failure assessment (SOFA) score in enrolled subjects towards historical comparators

Time: Screening, Day 8

---

Description: Change of lung involvement measurements between baseline and study visit day 8 will be compared with historical comparators from Hellenic Sepsis Study Group Database

Measure: Comparison of change of lung involvement measurements in enrolled subjects towards historical comparators

Time: Screening, Day 8

---

Description: Comparison of increase in pO2/FiO2 ratio towards historical comparators from Hellenic Sepsis Study Group Database

Measure: Comparison of pO2/FiO2 ratio in enrolled subjects towards historical comparators

Time: Screening, Day 8

---

Description: Change of Sequential organ failure assessment (SOFA) score on day 28 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)

Measure: Change of sequential organ failure assessment (SOFA) score

Time: Day 28

---

Description: Mortality on day 28

Measure: Rate of Mortality

Time: Day 28

---

Description: Mortality on day 90

Measure: Rate of Mortality

Time: Day 90

---

Description: Cytokine stimulation from peripheral blood mononuclear cells will be compared between days 0 and 4

Measure: Cytokine stimulation

Time: Screening, Day 4

---

Description: Gene expression of peripheral blood mononuclear cells will be compared between days 0 and 4

Measure: Gene expression

Time: Screening, Day 4

---

Description: Change of serum/plasma proteins between days 0 and 4

Measure: Serum/plasma proteins

Time: Screening, Day 4

---

Description: Classification of immune function of screened patients who are not enrolled in study drug since they are not characterized with MAS or immune dysregulation

Measure: Classification of the immune function

Time: Screening

---

Primary Outcomes

Description: Mortality at day 28

Measure: Mortality at day 28

Time: day 28

---

Secondary Outcomes

Description: severe complications (pulmonary embolism, acute kidney injury, myocarditis, cardiac arrest, liver failure, ventilator associated pneumonia) Yes / No

Measure: severe complications

Time: up to day 28

---

Description: Delay in imaging in hours

Measure: Imaging

Time: day 1

---

Description: delay in microbiological diagnosis in hours

Measure: Delay in Microbiological diagnosis

Time: day 1

---

Description: Antiviral therapy Yes / no

Measure: Antiviral therapy

Time: up to day 28

---

Description: Antibiotic therapy Yes / No

Measure: Antibiotic therapy

Time: day 28

---

Description: Covid-19 treatments Yes / No

Measure: Covid-19 treatments

Time: up to day 28

---

Description: number

Measure: Patients receiving renal replacement therapy

Time: up to day 28

---

Description: number

Measure: Patients receiving mechanical ventilation

Time: up to day 28

---

Description: Patient alive at day 28 : yes / No

Measure: Vital status

Time: day 28

---

Primary Outcomes

Description: Proportion of Family members with IES-R> 22 PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge of corresponding patient. It si a scale ranging from 0 to 88. Weiss, DS.; Marmar, CR. The impact of event scale - revised. In: Wilson, JP.; Keane, TM., editors.Assessing psychological trauma and PTSD. New York: Guilford Press; 1997. p. 399-411

Measure: PTSD Family members sup 22

Time: 90 days

---

Secondary Outcomes

Description: Among Family members PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)

Measure: PTSD Family members

Time: 90 days

---

Description: Among Patients PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)

Measure: PTSD Patients

Time: 90 days

---

Description: Among healthcare providers PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)

Measure: PTSD healthcare providers

Time: 2 months after official end of the Covid-19 peak

---

Description: Among Family members Symptoms of anxiety and depression using the HADS scale

Measure: HADS Family members

Time: 90 days

---

Description: Among Patients Symptoms of anxiety and depression using the HADS scale

Measure: HADS Patients

Time: 90 days

---

Description: Among Patients Mental and physical health-related quality of life as assessed by the SF36

Measure: SF36 Patients

Time: 90 days

---

Description: Among Family members Questionnaire describing their experience of the patient's ICU hospitalization

Measure: Questionnaire Family members

Time: 90 days

---

Description: Among Patients Questionnaire describing their experience of the patient's ICU hospitalization

Measure: Questionnaire Patients

Time: 90 days

---

Description: Among healthcare providers Questionnaire describing their experience of the patient's ICU hospitalization

Measure: Questionnaire healthcare providers

Time: 2 months after official end of the Covid-19 peak

---

Description: Among healthSymptoms of burnout on MBI scale as assessed by the Maslash Burnout Inventorycare providers

Measure: MBI healthcare providers

Time: 2 months after official end of the Covid-19 peak

---

Description: Job Strain as assessed by the Karasec instrument

Measure: Karasec instrument healthcare providers

Time: 2 months after official end of the Covid-19 peak

---

Primary Outcomes

Description: Survival without needs of ventilator utilization (including non invasive ventilation and high flow) at day 14. Thus, events considered are needing ventilator utilization (including Non Invasive Ventilation, NIV or high flow), or death. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.

Measure: Survival without needs of ventilator utilization at day 14

Time: 14 days

---

Description: Proportion of patients alive without non-invasive ventilation of high low at day 4 (WHO progression scale ≤ 5). A patient with new DNR order at day 4 will be considered as with a score > 5.

Measure: WHO progression scale ≤ 5

Time: 4 days

---

Description: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) at day 14 if patients have been intubated before day 14 ; or removal of NIV or high flow (for > 48h) if they were included under oxygen by NIV or High flow (score 6) and remained without intubation. Death or new DNR order (if given after the inclusion of the patient) will be considered as a competing event.

Measure: Cumulative incidence of successful tracheal extubation (defined as duration extubation > 48h) or withdrawal of NIV or high flow (for > 48h), at day 14

Time: 14 days

---

Description: Proportion of patients with a decrease of WHO score of at least 1 point at day 4

Measure: Decrease of at least one point in WHO progression scale score

Time: 4 days

---

Secondary Outcomes

Description: WHO progression scale: Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10.

Measure: WHO progression scale

Time: 7 and 14 days

---

Description: Overall survival.

Measure: Survival

Time: 14, 28 and 90 days

---

Measure: 28-day ventilator free-days

Time: 28 days

---

Description: arterial blood pH of <7.25 with a partial pressure of arterial carbon dioxide [Paco2] of ≥60 mm Hg for >6 hours.

Measure: Respiratory acidosis

Time: 4 days

---

Description: Evolution of PaO2/FiO2 ratio.

Measure: PaO2/FiO2 ratio

Time: day 1 to day 14

---

Description: Time to oxygen supply independency.

Measure: Time to oxygen supply independency

Time: 14 days

---

Description: Duration of hospitalization.

Measure: Duration of hospitalization

Time: 90 days

---

Description: Time to negative viral excretion.

Measure: Time to negative viral excretion

Time: 90 days

---

Description: Time to ICU discharge.

Measure: Time to ICU discharge

Time: 90 days

---

Description: Time to hospital discharge.

Measure: Time to hospital discharge

Time: 90 days

---

Primary Outcomes

Description: Secondary aggravation is defined as : a re-hospitalization or aggravation in hospitalization : development or increase in oxygen dependency, hemodynamic failure, and/or respiratory, death

Measure: Rate of secondary aggravation

Time: At 30 days of admission to the emergency department

---

Secondary Outcomes

Description: the number of leukocytes, lymphocytes, neutrophil polynuclear cells, CRP, fibrinogen, and the D-dimers.

Measure: Change of standart biological parameters

Time: Between baseline and at 30 days of admission to the emergency department

---

Measure: Change of Von willebrand factor (vWF) changes over time

Time: Between baseline and at 30 days of admission to the emergency department

---

Measure: Change of the Factor VIII (FVIII)

Time: Between baseline and at 30 days of admission to the emergency department

---

Measure: Prevalence of positivity of COVID-19 virus measured by PCR or serology

Time: At 30 days of admission to the emergency department

---

Primary Outcomes

Description: The blood specimen will be proceeded into peripheral blood mononuclear cells and plasma to be stored for testing. In brief, CD27+ memory B cells that can bind to a SARS-CoV-2 S protein bait will be sorted by flow cytometry and RNA will be extracted to obtain heavy and light chain sequences. Antibody sequences will be annotated using bioinformatics approaches, and candidate sequences will be cloned. Purified antibodies will be characterized and neutralization breadth and potency against SARS-CoV-2 and other related coronaviruses will be assessed using neutralization assays.

Measure: Number of antibodies against coronaviruses isolated and identified from patient samples

Time: Up to 12 months after collection visit

---

Primary Outcomes

Description: Outpatients who test positive for the Coronavirus 2019; number of days required in which they reach a 50 percent reduction in the cumulative 0-12 score symptom category of fever based on a 0-3 scale: 0 = ≤98.6, 1 = >98.6- 100.6, 2 = > 100.6 - 102.6, 3 = >102; Cough on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe; Shortness of Breath on a 0-3: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with walking on flat surface 3 = short of breath with getting dressed or daily activities; and Fatigue on a 0-3 scale: 0 = No fatigue/energetic, 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue. Each patient will have a composite score ranging from 0-12/day

Measure: Symptom Reduction

Time: 28 days

---

Secondary Outcomes

Description: The number of days required to reach a score of 0 from the symptom category of fever based on a 0-3 scale: 0 = ≤98.6, 1 = >98.6- 100.6, 2 = > 100.6 - 102.6, 3 = >102.6

Measure: Symptom Resolution: Fever

Time: 28 days

---

Description: The number of days required to reach a score of 0 from the symptom category of cough based on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe

Measure: Symptom Resolution: Cough

Time: 28 days

---

Description: The number of days required to reach a score of 0 from the symptom category of shortness of breath based on a 0-3 scale: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with walking on flat surface 3 = short of breath with getting dressed or daily activities

Measure: Symptom Resolution: Shortness of Breath

Time: 28 days

---

Description: The number of days required to reach a score of 0 from the symptom category of fatigue based on a 0-3 scale: 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue.

Measure: Symptom Resolution: Fatigue

Time: 28 days

---

Description: Total symptom composite score at day 5 of study supplementation: Symptom categories of fever based on a 0-3 scale: 0 = ≤98.6, 1 = >98.6- 100.6, 2 = > 100.6 - 102.6, 3 = >102; Cough on a 0-3 scale: 0 = no cough, 1 = mild, 2 = moderate, 3 = severe; Shortness of Breath on a 0-3: 0 = no shortness of breath, 1 = with moderate intensity exercise 2 = with walking on flat surface 3 = short of breath with getting dressed or daily activities; and Fatigue on a 0-3 scale: 0 = No fatigue/energetic, 1=mild fatigue, 2=moderate fatigue, 3=severe fatigue.

Measure: Day 5 Symptoms

Time: 5 days

---

Description: Differences in hospitalization events between the study arms

Measure: Hospitalizations

Time: 28 days

---

Description: Differences in severity of symptoms between study arms

Measure: Severity of Symptoms

Time: 28 days

---

Description: Differences in number of patients who were prescribed adjunctive medications for their diagnosis between study arms

Measure: Adjunctive Medications

Time: 28 days

---

Description: Differences in number of patients in study arms who experienced side effects from the supplements.

Measure: Supplementation Side Effects

Time: 28 days

---

Primary Outcomes

Description: Composite outcome

Measure: All-cause mortality or need of invasive mechanical ventilation

Time: 28 days

---

Secondary Outcomes

Description: Number of participants with adverse events with possible relation to study drug

Measure: Frequency of adverse events

Time: 90 days

---

Description: Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines

Measure: Frequency of severe adverse events

Time: 90 days

---

Description: Number of days to improvement of at least 2 categories relative to baseline on the ordinal scale. Categories are as follows: Death; Hospitalized, in intensive care requiring Extracorporeal Membrane Oxygenation (ECMO) or mechanical ventilation; Hospitalized, on non-invasive ventilation or high-flow oxygen device; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities

Measure: Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status

Time: 90 days

---

Description: Number of days without mechanical ventilation

Measure: Ventilator-free days

Time: 28 days

---

Description: Number of days without organ-failure

Measure: Organ failure-free days

Time: 28 days

---

Description: Number of days in ICU

Measure: Duration of ICU stay

Time: 90 days

---

Description: Number of deaths by any cause

Measure: Mortality rate

Time: 7, 14, 21, 28 and 90 days

---

Description: Days from the date of hospital admission for COVID-19 to the date of discharge

Measure: Length of hospital stay

Time: 90 days

---

Description: Days requiring supplement oxygen

Measure: Duration of supplemental oxygen

Time: 90 days

---

Primary Outcomes

Description: Antibody Titres IgG and IgM

Measure: Prevalence of SARS-CoV-2 antibody titres

Time: 5 weeks

---

Secondary Outcomes

Description: Re-Calculation including incidence of the general population

Measure: Prevalence of SARS-CoV-2 antibody titres after 3 Months

Time: 4 Months

---

Primary Outcomes

Description: Accuracy refers to the amount of agreement between the results of the antibody-based rapid test and the results of a PCR-based reference test

Measure: Clinical accuracy of the antibody-based rapid tests compared to PCR-based test result

Time: 1 year

---

Description: Accuracy refers to the amount of agreement between the results of the antibody-based rapid test and a clinical diagnosis of COVID-19

Measure: Clinical accuracy of the rapid tests based on Clinical diagnosis

Time: 1 year

---

Description: Clinical accuracy of the subject's visual interpretation of the test result vs image analysis from clinician

Measure: Self-test interpretation of result vs expert clinical image interpretation of result

Time: 1 year

---

Secondary Outcomes

Description: Subjects will complete a survey to rate the testing procedure for ease of use and convenience. The survey will ask subjects to rate the ease of use on a scale from 1 (easiest procedure to complete and understand) to 10 (most complicated and confusing procedure)

Measure: Ease of self-testing procedure

Time: 1 year

---

Primary Outcomes

Description: duration of mechanical ventilation via endotracheal tube

Measure: ventilator days

Time: up to 4 weeks

---

Secondary Outcomes

Description: number of days admitted to the ICU

Measure: Intensive care unit (ICU) length of stay

Time: up to 6 weeks

---

Description: number of patients requiring endotracheal intubation after extubation

Measure: need for re-intubation

Time: up to 6 weeks

---

Other Outcomes

Description: number of days spent in hospital during enrollment hospitalization

Measure: hospital length of stay

Time: up to 6 weeks

---

Description: death from any cause during hospitalization time of enrollment

Measure: hospital mortality

Time: up to 6 weeks

---

Description: death from any cause 90 day, 1year

Measure: long term mortality

Time: up to 1 year

---

Description: including ventilator associated pneumonia, GI hemorrhage, DVT/PE, sacral decubitus ulcer, delirium, ICU acquired weakness

Measure: ICU related complications

Time: up to 6 weeks

---

Description: measure the location (home, rehabilitation center, nursing home)

Measure: discharge location

Time: up to 90 days

---

Description: days alive and institution free

Measure: health care utilization

Time: up to 6 weeks

---

Description: ultrasound measurement at end expiration: enrollment, pre extubation, post extubation

Measure: diaphragm ultrasound thickness

Time: up to 6 weeks

---

Description: ultrasound measurement at end expiration and inspiration to calculate thickening fraction

Measure: diaphragm thickening fraction

Time: up to 6 weeks

---

Primary Outcomes

Description: Medical procedure in which a tube is placed into the windpipe (trachea) through the mouth.

Measure: Endotracheal intubation

Time: within 30 days of randomization

---

Secondary Outcomes

Description: Death

Measure: Mortality

Time: 30 days

---

Description: Number of days not receiving mechanical ventilation

Measure: Invasive mechanical ventilation free days

Time: 30 Days

---

Description: Number of days not receiving non-invasive mechanical ventilation

Measure: Non-invasive ventilation free days

Time: 30 days

---

Description: Number of days admitted to ICU

Measure: ICU length of stay

Time: 30 Days

---

Description: Number of days admitted to the hospital

Measure: Hospital length of stay

Time: 30 days

---

Description: defined as the difference in SpO2: FiO2 ratio. The difference in SpO2: FiO2 ratio.

Measure: Change in oxygenation

Time: 30 days

---

Description: Includes any of the following: accidental removal of intravenous access, vomiting, falls from bed, pressure injuries, or cardiac arrest.

Measure: Complications from proning,

Time: 30 days

---

Primary Outcomes

Description: Identification of risk factors present at the earliest stage of hospital care (i.e. in the ED) that warrant hospital admission.

Measure: Identification of risk factors present at the earliest stage of hospital care (i.e. in the ED) that warrant hospital admission.

Time: 6 months

---

Secondary Outcomes

Description: Determination of the course of the disease (days since onset of symptoms, nature of symptoms, e.g. fever, chills, headache) and the state at which patients present to the ED

Measure: Determination of the course of the disease (days since onset of symptoms, nature of symptoms, e.g. fever, chills, headache) and the state at which patients present to the ED

Time: 6 months

---

Description: Identification of the ratio of patients with mild or moderate to severe disease

Measure: Identification of the ratio of patients with mild or moderate to severe disease

Time: 6 months

---

Primary Outcomes

Description: Rate of hospitalization

Measure: Sub Study 1: Patients

Time: 21 days

---

Description: Rate of COVID-19 infection (confirmed by accepted testing methods) at 2 months

Measure: Sub Study 2: Health Care Workers

Time: 2 months

---

Secondary Outcomes

Description: any house hold member who has reported symptoms or test positive for COVID 19 during their 14 day active participation

Measure: Sub Study 1: Patients: Rate of secondary infection of co-inhabitants

Time: 14 days after enrollment of the household

---

Description: Assessment of any medical events that occur during the 14 day active period that is felt to be related to receipt of HCQ

Measure: Sub Study 1: Patients: Adverse Events

Time: 14 day active period

---

Description: If a test comes back negative, participant would be notified as such and told to destroy their pills as they are withdrawn

Measure: Sub Study 1: Patients: Negative for COVID-19

Time: up to 5 days after enrolling

---

Description: Any work time missed because the participant experienced COVID-like symptoms during their active 2 month period

Measure: Sub Study 2:Health Care Workers:Number of shifts missed

Time: up to ~60 days after enrollment

---

Description: Assessment of any medical events that occur during the ~60 day active period that is felt to be related to receipt of HCQ

Measure: Sub Study 2:Health Care Workers:Rate of adverse events

Time: up to ~60 days after enrollment

---

Description: if the participant gets COVID and has severe symptoms and hospitalized, end point reached if before the end of the 2 month period

Measure: Sub Study 2:Health Care Workers:Rate of hospitalization

Time: up to ~60 days after enrollment

---

Primary Outcomes

Description: presence of fibrosis on cardiac resonance and / or decreased functional capacity on ergospirometry

Measure: Fibrosis

Time: 12 months

---

Description: Decreased functional capacity on ergospirometers

Measure: Ergospirometers

Time: 12 monthes

---

Primary Outcomes

Description: Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs

Measure: Percentage of virus free subjects

Time: 7 days after initiation of trial

---

Description: Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .

Measure: Disease severity

Time: 6 days

---

Secondary Outcomes

Description: Number of subjects in each arm who are hospitalized for Covid 19 infection

Measure: Incidence of hospitalization

Time: 14 days

---

Description: Number of subjects in each arm who die secondary to Covid-19 infection

Measure: Incidence of Death

Time: 70 Days (10 weeks)

---

Description: Number of subjects in each arm who have confirmed Covid-19 infection

Measure: Incidence of confirmed SARS-CoV-2 Detection

Time: 14 days

---

Description: Number of subjects in each arm who discontinue or withdraw medication use for any reason

Measure: Incidence of all-cause study medication discontinuation or withdrawal

Time: 14 days

---

Description: Blood tests to determine level of immunity in each subject

Measure: Immunity to Covid-19

Time: 70 days (10 weeks)

---

Primary Outcomes

Description: As determined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria

Measure: Incidence of AKI

Time: Within 7 days after admission

---

Secondary Outcomes

Description: Serial biomarker assessment

Measure: Renal function changes during hospital stay

Time: from hospital admission til discharge up to 3 months

---

Description: As determined by KDIGO criteria

Measure: Incidence of chronic kidney disease

Time: 3 months post-hospital admission

---

Primary Outcomes

Description: To investigate the safety of in-hospital thromboprophylaxis with twice-daily low-dose enoxaparin thromboprophylaxis as measured by cumulative incidence of ISTH-defined clinically-relevant bleeding events during hospitalization. Clinically relevant bleeding episodes may include any of the following: 1) fatal bleeding; 2) clinically overt bleeding associated with a decline in hemoglobin of ≥2g/dL in a 24h period; 3) retroperitoneal, pulmonary, or central nervous system bleeding; 4) bleeding requiring surgical intervention in an operating suite; 5) bleeding for which a blood product is administered (blood product administration not directly attributable to the patient's underlying condition); 6) bleeding that requires medical or surgical intervention to restore hemostasis, other than in an operating suite.

Measure: Safety of in-hospital thromboprophylaxis

Time: Day 30

---

Secondary Outcomes

Description: The median twice-daily enoxaparin dose, as measured in mg/kg, required to achieve a 4 hour post-dose anti-factor Xa level of 0.20-0.49 anti-Xa U/mL in children hospitalized with COVID-19, and to compare dose-requirements by age group (birth to <1 year old, 1-<6 years old, 6-<13 years old, and 13-<18 years old).

Measure: Median twice-daily enoxaparin dose

Time: 4 hours post initial dose

---

Other Outcomes

Description: To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by the proportion of serial D-dimer levels obtained at standardized time points that are <2 times the upper limit of normal (<2x ULN) values for age.

Measure: Efficacy of in-hospital thromboprophylaxis as measured by the proportion of serial D-dimer levels

Time: Enrollment, Day 1, Day 2, and Day 3, 7, and 14 if still hospitalized

---

Description: To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by confirmed HA-VTE.

Measure: Efficacy of in-hospital thromboprophylaxis as measured by confirmed HA-VTE

Time: Day 30

---

Description: To investigate, on a preliminary basis, the efficacy of in-hospital thromboprophylaxis with twice-daily enoxaparin in children hospitalized with COVID-19, as measured by median duration of in-hospital increased respiratory support (new requirement for high-flow nasal cannula, non-invasive ventilation, and/or mechanical ventilation, relative to any at-home baseline requirement).

Measure: Efficacy of in-hospital thromboprophylaxis as measured by median duration of increased respiratory support

Time: Day 30

---

Primary Outcomes

Description: The primary objective of the study will be evaluated by the proportion of patients contaminating the air 1 meter from their face. The contamination will be assessed by quantifying the viral RNA by RT-PCR on a 600-liter air sample aspirated by a Coriolis® system. This sample will be taken within 48 hours after the confirmation of SARS-Cov-2 infection, documented by RT-PCR.

Measure: Estimate the proportion of patients hospitalized in intensive care for a SARS-Cov-2 viral lung infection and contaminating their environment at 1 meter.

Time: within 48 hours of the confirmation of SARS-Cov-2 infection documented by RT-PCR

---

Primary Outcomes

Description: nM;

Measure: ETP (AUC) without rhThrombomodulin (rhTM)

Time: 6 months

---

Description: nM;

Measure: ETP (AUC) with rhThrombomodulin (rhTM)

Time: 6 months

---

Description: Ratio of endogenous thrombin potential (ETP) with rhTM to ETP without rhTM

Measure: ETP-ratio

Time: 6 months

---

Description: Comparison of ETP-ratios from ICU patients and ETP-ratios from citrated plasma samples from healthy donors

Measure: ETP-Normalisation

Time: 6 months

---

Primary Outcomes

Measure: Proportion of participants with an occurrence of hospitalization

Time: From inclusion (day0) to day 14

---

Description: Proportion of participants with an occurrence of death

Measure: Death

Time: From inclusion (day0) to day 14

---

Secondary Outcomes

Measure: Proportion of hospitalizations, overall and by cause, in each group

Time: From inclusion (day0) to day 28

---

Description: Proportion of deaths, overall and by cause, in each group

Measure: Death and causes of death

Time: From inclusion (day0) to day 28

---

Measure: Proportion of intensive care hospitalizations, overall and by cause, in each group

Time: From inclusion (day0) to day 28

---

Measure: Proportion of participants with negative nasopharyngeal SARS-CoV-2 RT-PCR

Time: day 7 and day 14

---

Measure: Proportion of participants with a loss of autonomy evaluated by the ADL and IADL scale

Time: day 14 and day 28

---

Description: Evolution of Haematological markers in each group : Complete Blood Count, prothrombin level, INR

Measure: Haematological markers evolution

Time: from inclusion (day 0) to day 7 and day 14

---

Description: Evolution of Biochemical markers in each group : ferritin, serum creatinine, urea, sodium, potassium, chlorine, calcium, magnesium, albumin, bicarbonates / tCO2, LDH, CPK, ASAT, ALAT, uricemia

Measure: Biochemical markers evolution

Time: from inclusion (day 0) to day 7 and day 14

---

Description: Evolution of Inflammatory markers in each group : PCT, CRP

Measure: Inflammatory markers evolution

Time: from inclusion (day 0) to day 7 and day 14

---

Description: Evolution of immunological markers in each group : B ans T Cells phenotypic profiles

Measure: Immunological markers evolution

Time: from inclusion (day 0) to day 7 and day 14

---

Description: Number and proportion of grade 1,2,3,4 adverse events in each group

Measure: Adverse events

Time: from inclusion (day 0) to day 14

---

Description: Number and proportion of grade 1,2,3,4 adverse events in each group

Measure: Adverse reactions

Time: from inclusion (day 0) to day 14

---

Description: Plasma concentration of the study drugs at D7

Measure: Plasma concentration

Time: day 7

---

Description: Acceptability of the treatment by participant will be assessed with an interview

Measure: Acceptability of the treatment

Time: from inclusion (day 0) to day 10

---

Primary Outcomes

Description: TP/TP+FN (TP= True Positive; FN = False Negative)

Measure: Sensibility

Time: Salivary test will be interpreted after 10 minutes; the nasopharyngeal swab after 6 hours; sensitivity recorded through study completion, an average of 2 months.

---

Description: TN/TN+FP (TN= True Negative; FP= False Positive)

Measure: Specificity

Time: Salivary test will be interpreted after 10 minutes; the nasopharyngeal swab after 6 hours; specificity recorded through study completion, an average of 2 months.

---

Primary Outcomes

Description: The primary study endpoint is the ratio of patients who will not develop serious respiratory failure SRF until day 14. Patients dying before study visit of day 14 are considered non-achieving the primary endpoint.

Measure: The ratio of patients who will not develop serious respiratory failure (SRF)

Time: Visit study day 14

---

Secondary Outcomes

Description: Evaluation of clinical data (pO2/FiO2 and need of mechanical ventilation) between baseline and study visit day 14 will be compared with historical comparators from Hellenic Sepsis Study Group Database

Measure: Comparison of the rate of patients who will not develop serious respiratory failure (SRF) until day 14 with historical comparators from Hellenic Sepsis Study Group Database

Time: Visit study day 14

---

Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 7

Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 7

Time: Visit study day 1, visit study day 7

---

Description: Change of scoring for respiratory symptoms (evaluation of cough, chest pain, shortness of breath and sputum) in enrolled subjects between days 1 and 14

Measure: Change of scoring for respiratory symptoms in enrolled subjects between days 1 and 14

Time: Visit study day 1, visit study day 14

---

Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 7 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)

Measure: Change of SOFA score in enrolled subjects between days 1 and 7

Time: Visit study day 1, visit study day 7

---

Description: Change of Sequential organ failure assessment (SOFA) score of enrolled subjects between days 1 and 14 (Sequential organ failure assessment range 0-24, high score associated with worst outcome)

Measure: Change of Sequential organ failure assessment (SOFA) score in enrolled subjects between days 1 and 14

Time: Visit study day 1, visit study day 14

---

Description: Change of cytokine stimulation from peripheral blood mononuclear cells of enrolled subjects will be compared between days 1 and 7

Measure: Change of cytokine production between days 1 and 7

Time: Visit study day 1, visit study day 7

---

Description: Change of plasma inflammatory mediators measured levels will be compared between days 1 and 7

Measure: Change of plasma inflammatory mediators levels between days 1 and 7

Time: Visit study day 1, visit study day 7

---

Primary Outcomes

Description: Relative abundance of bacterial classes within taxonomic phyla and, more broadly, within their domain will be analyzed by sequencing the gut microbiome. These data will then be categorized among specific gastrointestinal disease types.

Measure: Correlation of Microbiome to Disease via Relative Abundance Found in Microbiome Sequencing

Time: One year

---

Secondary Outcomes

Description: To validate the methods used to sequence samples

Measure: Validation of Sequencing Methods

Time: One year

---

Primary Outcomes

Description: SF-36 score

Measure: Quality of Life score

Time: up to 12 months after discharge

---

Secondary Outcomes

Description: Montreal Cognitive Assessment (MoCA) score

Measure: cognitive dysfunction

Time: up to 12 months after discharge

---

Description: (FSS-ICU)

Measure: Functional Status Score

Time: up to 12 months after discharge

---

Description: MRC neuromuscular Assessment

Measure: Physical Disability

Time: up to 12 months after discharge

---

Description: Impact Event Score

Measure: Psychological Sequelae

Time: up to 12 months after discharge

---

Other Outcomes

Description: hospital anxiety and depression scale

Measure: hospital anxiety and depression

Time: up to 12 months after discharge

---

Description: including ventilator associated pneumonia, GI hemorrhage, Deep Vein Thrombosis (DVT) /Pulmonary Embolus (PE), sacral decubitus ulcer, delirium, ICU acquired weakness

Measure: ICU related complications

Time: hospitalization up to 6 weeks

---

Description: measure the location (home, rehabilitation center, nursing home

Measure: hospital discharge location

Time: hospital discharge up to 6 weeks

---

Description: number of days admitted to the ICU

Measure: lCU length of stay

Time: hospitalization up to 6 weeks

---

Description: number of days admitted to the hospital

Measure: hospital length of stay

Time: hospitalization up to 6 weeks

---

Primary Outcomes

Description: To use multifaceted participant data consisting of participant reported outcomes, environmental surface and presence or absence of COVID-19 based on testing results, prescription medications (including off-label use), claims, lab, and medical record data to develop population-based models of disease risk, short and long-term outcomes, and efficacy of interventions and prevention measures.

Measure: Development of population-based models of disease risk

Time: Up to 10 years

---

Description: To leverage geolocation and lab results to provide population-level real-time data regarding disease burden at the community, state and national levels.

Measure: Relation between disease burden and geolocation

Time: Up to 10 years

---

Description: To specifically identify medications and regimens that address disease symptoms

Measure: Effect of medications on symptoms of COVID19

Time: Up to 10 years

---

Description: To specifically identify medications and regimens that treat and reduce disease severity.

Measure: Effect of medications on disease severity of COVID19

Time: Up to 10 years

---

Secondary Outcomes

Description: To identify regional variations in disease incidence and outcomes.

Measure: Rate of COVID19 infection and disease outcomes

Time: Up to 10 years

---

Description: To understand long-term outcomes such as risk of pulmonary and cardiovascular disease complications.

Measure: Effect of COVID19 on health outcomes

Time: Up to 10 years

---

Description: To conduct long-term follow up of individuals who tested positive for COVID-19 compared to demographically matched individuals that did not.

Measure: Long-term follow up and recontact

Time: Up to 10 years

---

Primary Outcomes

Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay

Measure: Incidence of symptomatic COVID-19 infection in healthcare workers

Time: 12 weeks

---

Secondary Outcomes

Description: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection

Measure: Absenteeism from work due to COVID-19

Time: 12 weeks

---

Description: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)

Measure: Severity of COVID-19 infection

Time: 12 weeks

---

Primary Outcomes

Description: The performance of the COVID-19 IgG Dia-Pro serological test is evaluated in terms of sensitivity/specificity.

Measure: Serological test evaluation

Time: 1 day

---

Secondary Outcomes

Description: Population seroprevalence among hospital staff (caregivers and non-caregivers) in Quimper Hospital is assessed

Measure: Population seroprevalence

Time: 1 month

---

Primary Outcomes

Description: The primary outcome of the study will be days alive and outside the hospital (DAOH) at 30 days. This endpoint will be calculated for each included patient and the calculation will be from the date of randomization to the 30-day post-randomization. The DAOH endpoint represents the follow-up time (30 days) subtracted from the hospitalization days and/or the days between death and the end of follow-up.

Measure: Median days alive and out of the hospital

Time: 30 days

---

Secondary Outcomes

Description: Cardiovascular outcomes such as evolution with acute myocardial infarction, stroke, myocarditis, pericarditis, arrhythmias requiring treatment, thromboembolic phenomena, increase in troponin and D-dimer, respiratory failure, hemodynamic decompensation, sepsis, renal failure and death.All events will be reported according to CTCAE 4.0

Measure: Number of participants with adverse cardiovascular outcomes and new worsening heart failure

Time: 30 days

---

Description: Evaluation of test results troponin, NT-ProBNP, BNP, and D-dimer will also be assessed as secondary outcome.

Measure: Cardiovascular biomarkers related to COVID-19

Time: up to 30 days

---

Primary Outcomes

Description: Number and severity of adverse events

Measure: Phase 1: Frequency and Severity of Adverse Events (AE)

Time: Up to 12 months

---

Description: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR

Measure: Time to Clearance of SARS-CoV-2

Time: Up to 12 months

---

Description: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR

Measure: Rate of Clearance of SARS-CoV-2

Time: Up to 12 months

---

Description: Time from the date of randomization to the first date of clinical improvement of cough.

Measure: Time to Clinical Improvement of cough

Time: Up to 28 days

---

Description: Time from the date of randomization to the first date of clinical improvement of fever

Measure: Time to Clinical Improvement of fever

Time: Up to 28 days

---

Description: Time from the date of randomization to the first date of clinical improvement of radiological evaluation of disease related chest x-ray

Measure: Time to Clinical Improvement in radiological evaluation of disease related chest x-ray

Time: Up to 28 days

---

Description: Proportion of subjects who achieved clinical improvement of fever

Measure: Rate of Clinical Improvement of fever

Time: Up to 28 days

---

Description: Proportion of subjects who achieved clinical improvement of cough

Measure: Rate of Clinical Improvement of cough

Time: Up to 28 days

---

Description: Proportion of subjects who achieved clinical improvement of radiological evaluation of disease related chest x-ray

Measure: Rate of Clinical Improvement of radiological evaluation of disease related chest x-ray

Time: Up to 28 days

---

Description: Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).

Measure: Time to Pulmonary Clearance

Time: Up to 28 days

---

Description: Proportion of subjects who achieve pulmonary clearance

Measure: Rate of Pulmonary Clearance

Time: Up to 28 days

---

Description: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.

Measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score

Time: Up to 28 days

---

Secondary Outcomes

Description: Number and severity of adverse events

Measure: Phase 2: Frequency and Severity of Adverse Events (AE)

Time: up to 12 months

---

Description: Time to medical discharge as an assessment of overall clinical benefit

Measure: Overall Clinical Benefit by time to medical discharge

Time: up to 12 months

---

Description: Hospital utilization will be measured as an assessment of overall clinical benefit

Measure: Overall Clinical Benefit by hospital utilization

Time: up to 12 months

---

Description: Mortality rate will be measured as an assessment of overall clinical benefit

Measure: Overall Clinical Benefit by measuring mortality rate

Time: up to 12 months

---

Primary Outcomes

Description: Elevation of creatine kinase during hyperacute phase of corona virus disease 2019 (Covid-19)

Measure: Rate of elevated creatine kinase in hyperacute phase

Time: 1 week

---

Secondary Outcomes

Description: Elevation of creatine kinase during hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)

Measure: Rate of elevated creatine kinase

Time: 24 months

---

Description: Two-peak elevation of creatine kinase during acute phase of corona virus disease 2019 (Covid-19)

Measure: Rate of two-peak elevation of creatine kinase during acute phase

Time: 30 days

---

Description: Presence of myositis-specific antibodies on admission, at two weeks, and at end of follow-up

Measure: Rate of myositis-specific antibodies

Time: 24 months

---

Description: Presence of antimyocardial antibodies on admission, at two weeks, and at end of follow-up

Measure: Rate of antimyocardial antibodies

Time: 24 months

---

Description: Level of creatine kinase elevation in the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19) assessed by the area under the curve (AUC)

Measure: Area under the curve (AUC) of elevated creatine kinase

Time: 24 months

---

Description: Maximal value of creatine kinase elevation in the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)

Measure: Peak-levels of elevated creatine kinase

Time: 24 months

---

Description: Maximal value of troponin in the acute phase of corona virus disease 2019 (Covid-19)

Measure: Peak-levels of troponin

Time: 30 days

---

Description: Maximal value of urine myoglobin in the acute of corona virus disease 2019 (Covid-19)

Measure: Peak-levels of urine myoglobin

Time: 30 days

---

Description: Muscle hyperechogenicity in the upper and lower extremities, the accessory respiratory serratus anterior muscle, and abdominal wall according to qualitative ultrasound assessment (Heckmatt score) during the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)

Measure: Rate of muscle hyperechogenicity

Time: 24 months

---

Description: Peak-muscle hyperechogenicity in the upper and lower extremities, the accessory respiratory serratus anterior muscle, and abdominal wall according to qualitative ultrasound assessment (Heckmatt score) during the hyperacute, acute, subacute and chronic phase of corona virus disease 2019 (Covid-19)

Measure: Peak-muscle hyperechogenicity

Time: 24 months

---

Primary Outcomes

Description: Presence or absence of IgG antibodies to SARS-CoV2

Measure: Percentage of Asymptomatic patients with an IgG response from SARS-CoV-2 infection.

Time: at enrollment

---

Secondary Outcomes

Description: swab for presence of SARS-CoV-2 virus

Measure: Percentage of Asymptomatic patients with viral presence of SARS-CoV-2 infection.

Time: at enrollment

---

Primary Outcomes

Measure: provide proof-of-concept that (longitudinal) B cell repertoire mining allows identification of emerging virus specific B cell receptor variable regions.

Time: 4 months

---

Secondary Outcomes

Measure: study evolutions in B and T cell repertoires to understand COVID-19 specific immune responses fundamentally.

Time: every 7 days during hospitalization a bloodsample is taken

---

Measure: clinical and epidemiological description of UZA hospitalized COVID-19 patients

Time: at hospitalization

---

Primary Outcomes

Description: assessed by positive polymerase chain reaction (PCR) from routine nasal swabs (performed every 28 days)

Measure: Cumulative number of severe acute respiratory syndrome corona virus 2 (SARS-COV-2) infections

Time: 12 weeks after initiation of therapy

---

Secondary Outcomes

Description: defined as combined endpoint of hospitalization rate or death

Measure: Number of severe COVID-19 cases

Time: 12 weeks after initiation of therapy

---

Description: grading as outlined by the world health organization (WHO)

Measure: Severity of COVID-19 cases

Time: 12 weeks after initiation of therapy

---

Description: significant clinical and laboratory abnormalities according to CTCAE criteria

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time: 12 weeks after initiation of therapy

---

Description: other than COVID-19

Measure: Number of viral and bacterial infections

Time: 12 weeks after initiation of therapy

---

Description: Development of azithromycin-resistant bacterial strains as assessed by nasal swabs test

Measure: Number of participants with azithromycin-resistant bacterial strains in nasal swabs test

Time: 12 weeks after initiation of therapy

---