Primary Outcomes

Description: An Acute Exacerbation in a COPD patient is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough, and/or sputum production and beyond normal day to day variations, that is acute in onset and may warrant a change in regular medication in a patient with underlying COPD The Means and Confidence Intervals (CI) were estimated using the Negative Binomial model taking into account time to follow up. Estimated exacerbations were presented as mean number of exacerbations per (/) subject/ year.

Measure: Mean Estimated Number of Acute Exacerbation of COPD (AECOPD)

Time: During year 1

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Description: Bacterial pathogens assessed were: Haemophilus influenzae (Hi), Moraxella catarrhalis (Mcat), Steptococcus pneumoniae (Sp), Staphylococcus Aureus (Sta), Pseudomonas aeruginosa (Psa), any or other. For each bacteria, the means and CIs were estimated from Negative Binomial model taking into account the follow up time.Estimated exacerbations were presented as mean number of exacerbations/ subject/ year.

Measure: Mean Estimated Number of AECOPD With Sputum Containing Bacterial Pathogens

Time: During Year 1

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Description: Bacterial pathogens assessed, by culture, were: Haemophilus influenzae (Hi), Moraxella catarrhalis (Mcat), Streptococcus pneumoniae (Sp), Staphylococcus aureus (Sta), Pseudomonas aeruginosa (Psa), any bacteria or other bacteria. Overall exacerbation rate is the average number of exacerbations for each subject during their time in the study.

Measure: Overall AECOPD Exacerbation Rate for Any and Specific Bacterial Pathogens in Sputum

Time: During Year 1

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Secondary Outcomes

Description: Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for any bacteria and Hi.

Measure: Number of Sputum Samples Positive for Specific Pathogens - Any Bacteria and Hi

Time: During Year 1

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Description: Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for Mcat and Sp.

Measure: Number of Sputum Samples Positive for Specific Pathogens - Mcat and Sp

Time: During Year 1

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Description: Sputum samples were tested by bacterial species (any bacteria, Hi, Mcat, Sp, Sta, Psa and other bacteria), or overall and were obtained from culture at each visit (enrollment, any stable visit, any exacerbation visit, any mild exacerbation visit, any moderate exacerbation visit, any severe exacerbation visit). This endpoint presents results for Sta, Psa and other bacteria.

Measure: Number of Sputum Samples Positive for Specific Pathogens - Sta, Psa and Other Bacteria

Time: During Year 1

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Description: The number of days between 2 consecutive exacerbations, as estimated by the investigator, was calculated only whenever the first exacerbation had an end date.

Measure: Mean Number of Days Between 2 Consecutive AECOPDs

Time: During Year 1

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Description: The exacerbations of chronic pulmonary disease tool version 1.0 (EXACT) is a validated self-administered instrument that evaluates the effects of pharmacologic treatment on acute exacerbations of COPD. Analyses of exacerbations in relation to morning or evening EXACT-PRO e-diaries were presented as follows: descriptive statistics on the EXACT daily scores tabulated at enrolment, at any stable and at any, mild, moderate or severe exacerbation visit. EXACT-PRO contains 14 questions with scores ranging from 0 to 4, where 0= best outcome while 4= worse outcome.

Measure: Change From Baseline EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Scores at Enrollment and Any AECOPD Visit

Time: During Year 1

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Description: The COPD assessment test (CAT) is a validated self-administered instrument designed to provide a simple and reliable measure of health status in COPD patients. Its properties have been shown to be similar to the St George's respiratory questionnaire (SGRQ). The CAT comprises 8 items and has a scoring range of 0-40, 0= most positive answer and 40= most negative answer. In this study, the subjects were to complete the CAT questionnaire every 3 months.

Measure: Change From Baseline COPD Assessment Test (CAT) Scores at Enrollment and Any AECOPD Visit

Time: During Year 1

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Description: The NEADL assessed (quarterly in the present study) the ease or difficulty in performing extended activities of daily living. The NEADL scale contains 22 items, each measured on a 4-point Likert scale. There are four dimensions: mobility (6 items); kitchen (5 items); domestic (5 items); leisure (6 items). These are summed producing a total score reflecting general functioning. Each of the 22 individual items had 2 possible scores (0 or 1). Therefore, the range of the NEADL score was 0 to 22. Lower scores indicate greater levels of disability while higher scores indicate greater independence.

Measure: Change From Baseline COPD Nottingham Extended Activities of Daily Living Scale (NEADL) Scores at Enrollment and Any AECOPD Visit

Time: During Year 1

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Description: The EQ-5D is an established measure of generic health outcome that provides a simple descriptive profile and a single index value that can be used in clinical and economic evaluation of healthcare and in population surveys. Its current format is 3-level and 5 dimensional (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was derived from the ratings recorded every 3 months for each of the five individual items (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). The EQ-5D index was 0 (worst health state) to 100 (best health state). The negative numbers presented represent a decrease from baseline values and a worsening of health.

Measure: Change From Baseline COPD EQ-5D Index and Visual Analogue Scale (VAS) Scores at Enrollment and Any AECOPD Visit

Time: During Year 1

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Description: AECOPD health care type included: general practitioners (other than the study doctor), pneumologists, other specialists, hospital emergency department, home care nurses, pulmonary rehabilitation programs and/or nutrition advices.

Measure: Number of Subjects Receiving Various Health Care Types During AECOPD

Time: During Year 1

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Description: Serious adverse events (SAEs) include medical occur-rences that result in death, are life threatening, require hospitali-zation or prolongation of hospitalization or result in disabil-ity/incapacity.

Measure: Number of Subjects With Serious Adverse Events (SAEs) Possibly Related/Linked to Withdrawal

Time: During Year 1

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Description: Bacterial pathogens assessed, by PCR assay were: Hi, Mcat, Sp, Sta, Psa, Streptococcus pyogenes (Spyo) and any bacteria.

Measure: AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum , by Polymerase Chain Reaction (PCR) Assay

Time: During Year 1

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Description: Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus.

Measure: AECOPD Rate With Overall and Specific Viral Pathogens in Sputum

Time: During Year 1

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Description: Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Mild exacerbations were defined as worsening symptoms of COPD that were self-managed by the patient.

Measure: Mild-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum

Time: During Year 1

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Description: Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Moderate exacerbations were defined as worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics.

Measure: Moderate-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum

Time: During Year 1

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Description: Viral pathogens assessed were: respiratory syncytial virus (RSV), parainfluenza virus (PIV), entero rhinovirus (ENV), human metapneumovirus (HMP), influenza virus (INV), adenovirus (ADV), coronavirus (CRV), human bocavirus (HBoV) and any virus. Severe exacerbations were defined as worsening symptoms of COPD that required treatment with in-patient hospitalisation or home care intervention.

Measure: Severe-AECOPD Rate With Overall and Specific Viral Pathogens in Sputum

Time: During Year 1

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Description: An Acute Exacerbation in a COPD patient is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough, and/or sputum production and beyond normal day to day variations, that is acute in onset and may warrant a change in regular medication in a patient with underlying COPD. AECOPD severity was assessed as: any, mild, moderate and severe. Any = any COPD symptom regardless of severity. Mild = Worsening symptoms of COPD that are self-managed by the patient. Moderate = Worsening symptoms of COPD that require treatment with oral corticosteroids and/or antibiotics. Severe = Worsening symptoms of COPD that require treatment with in-patient hospitalisation or home care intervention.

Measure: AECOPD Rate With Overall and Specific Bacterial Pathogens in Sputum by Severity

Time: During Year 1

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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

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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

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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

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Primary Outcomes

Description: Bacterial pathogens, as identified by bacteriological methods, including (but not necessarily limited to) Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii.

Measure: Occurrence of potential bacterial in sputum of stable COPD patients.

Time: Over the course of 1 year

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Description: Bacterial pathogens, as identified by bacteriological methods, including (but not necessarily limited to) Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii.

Measure: Occurrence of potential bacterial in sputum during AECOPD.

Time: Over the course of 1 year

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Description: Viral pathogens, as identified by PCR, including (but not necessarily limited to) Respiratory syncytial virus (RSV), parainfluenza virus, enterovirus/ rhinovirus, metapneumovirus, influenza virus, adenovirus, bocavirus and coronavirus and by rhinovirus quantitative RT-PCR.

Measure: Occurrence of viral pathogens in sputum of stable COPD patients.

Time: Over the course of 1 year

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Description: Viral pathogens, as identified by PCR, including (but not necessarily limited to) Respiratory syncytial virus (RSV), parainfluenza virus, enterovirus/ rhinovirus, metapneumovirus, influenza virus, adenovirus, bocavirus and coronavirus and by rhinovirus quantitative RT-PCR.

Measure: Occurrence of viral pathogens in sputum during AECOPD.

Time: Over the course of 1 year

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Secondary Outcomes

Description: Including (but not necessarily limited to) H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus and P. aeruginosa. The proportion of sputum samples obtained at each confirmed stable/AECOPD visit and positive for specific bacterial pathogens by PCR will be computed with 95% confidence intervals.

Measure: Occurrence of potential bacterial pathogens in sputum of stable COPD patients and during AECOPD, as measured by real-time qualitative PCR/ quantitative PCR and compared to data from bacteriological methods.

Time: Over the course of 1 year

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Description: The proportion of sputum samples obtained at each AECOPD visit and positive for specific bacterial/viral pathogens by bacteriological methods and PCR, respectively (overall and by bacterial/viral species) will be computed with 95% confidence intervals by any severity (mild, moderate and severe).

Measure: Occurrence of potential bacterial and viral pathogens (overall and by species) in sputum during AECOPD by severity of AECOPD.

Time: Over the course of 1 year

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Description: The proportion of sputum samples obtained at each confirmed stable visit and positive for bacterial/viral pathogens by bacteriological methods and PCR, respectively (overall and by bacterial / viral species) will be computed with 95% confidence intervals by Gold grade at enrolment.

Measure: Occurrence of potential bacterial and viral pathogens (overall and by species) in sputum of stable COPD patients by GOLD grade.

Time: Over the course of 1 year

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Description: The following incidence rates will be computed, with 95% confidence intervals (CI): All-cause AECOPD. AECOPD having sputum containing bacterial pathogens found by PCR or by bacteriological methods or by both methods (overall and by, but not limited to, the following bacterial species: H. influenzae, M. catarrhalis, S. pneumoniae, S. aureus, and P. aeruginosa). The 95% CI of the incidence rate will be computed using a model which accounts for repeated events. The incidence rates described above will also be computed for mild, moderate severe AECOPD and by GOLD grade at enrolment.

Measure: Incident rate (per subject per year) of any AECOPD overall and by GOLD grade.

Time: Over the course of 1 year

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Description: Classification of severity according to the intensity of medical intervention required: mild: controlled with an increase in dosage of regular medications; moderate: requires treatment with systemic corticosteroids and/ or antibiotics; severe: requires hospitalisation.

Measure: Number of mild, moderate or severe AECOPD overall and by GOLD grade.

Time: Over the course of 1 year

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Description: Descriptive statistics (median, mean, range, standard deviation, first and third quartiles) on the number of days of AECOPD episodes will be presented.

Measure: Number of days of AECOPD episodes overall and by AECOPD severity.

Time: Over the course of 1 year

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Description: Descriptive statistics (median, mean, range, standard deviation, first and third quartiles) on the CAT scores will be tabulated at each respective visit.

Measure: COPD assessment test (CAT) score in stable COPD patients and during AECOPD.

Time: Over the course of 1 year

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Description: Descriptive statistics (median, mean, range, standard deviation, first and third quartiles) on the SGRQ-C scores will be tabulated at each respective visit.

Measure: St. George's Respiratory Questionnaire (SGRQ-C) score in stable COPD patients.

Time: Over the course of 1 year

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Description: The spirometric classification of airflow limitation in COPD patients is based on post-bronchodilator FEV1. Summary statistics (mean, median, standard deviation, maximum and minimum) on post bronchodilator FEV1% of predicted normal value will be tabulated at each respective visit.

Measure: Forced expiratory volume in 1 second (FEV1%) of predicted normal value in stable COPD patients.

Time: At Pre-Month 0 and Month 12

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Description: Healthcare use for each COPD patient will be obtained through review of the subject's medical record (aided by subject self-reporting). Healthcare utilisation includes all unscheduled visits to a physician office, visits to urgent care, visits to emergency department, and hospitalizations.

Measure: Assessment of the Healthcare utilization.

Time: Over the course of 1 year

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Primary Outcomes

Description: The change from baseline in number of airway submucosal inflammatory cells/mm2 of bronchoscopic biopsies.

Measure: The change from baseline in number of airway submucosal inflammatory cells/mm2 of bronchoscopic biopsies.

Time: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.

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Secondary Outcomes

Description: The change in reticular basement membrane (RBM) thickness from baseline, determined by microscopic evaluation of bronchoscopic biopsies

Measure: The change in reticular basement membrane (RBM) thickness from baseline, determined by microscopic evaluation of bronchoscopic biopsies

Time: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.

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Description: The change in % airway epithelial integrity from baseline determined by microscopic evaluation of bronchoscopic biopsies

Measure: The change in % airway epithelial integrity from baseline determined by microscopic evaluation of bronchoscopic biopsies

Time: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.

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Description: The change in number of airway submucosal inflammatory cells per mm2 from baseline, across the spectrum of T2 status, determined by microscopic evaluation of bronchoscopic biopsies

Measure: The change in number of airway submucosal inflammatory cells per mm2 from baseline, across the spectrum of T2 status, determined by microscopic evaluation of bronchoscopic biopsies

Time: Baseline, End of Treatment (EoT). The EoT will be performed at Week 28 for the majority of subjects but may be performed at later timepoints for some subjects (Week 32, etc.) due to up to 6 additional doses added during the Covid-19 pandemic.

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Primary Outcomes

Description: Dichotomous categorical variable measured by "yes" or "no" responses

Measure: COVID-19 disease diagnosis

Time: Change from Baseline COVID-19 disease diagnosis at 8 weeks

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Secondary Outcomes

Description: Dichotomous categorical variable measured by "slight" or "severe" responses

Measure: COVID-19 disease symptoms severity

Time: Change from Baseline COVID-19 disease symptoms severity at 8 weeks

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Description: Polytomous categorical variable measured by adverse effects responses

Measure: Adverse effects

Time: Change from Baseline adverse effects at 8 weeks

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Primary Outcomes

Description: breath sample collection

Measure: To perform a study in patients with clinical features of pneumonia/chest infection to identify a signature of Covid-19 pneumonia in patients exposed to SARS-CoV-2, compared to unexposed patients or those without.

Time: up to daily during hospital admission

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Secondary Outcomes

Description: breath sample collection

Measure: Detection of markers of Covid-19 pneumonia in non-invasive breath samples.

Time: multiple samples up to 60 days

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Description: breath sample collection

Measure: Relationship of this biomarker signature to the presence of SARS-CoV-2 in nasal and throat swabs.

Time: multiple samples up to 60 days

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Description: breath sample collection

Measure: Subsequently, the signature's relationship to other biomarkers of SARS-CoV-2 infection which are currently being explored

Time: multiple samples up to 60 days

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Description: breath sample collection

Measure: In a smaller group of participants, ideally daily non-invasive breath samples will be collected to determine if there are changes between SARS-CoV-2 positive patients and those that are negative until hospital discharge or undue participant burden .

Time: multiple samples up to 60 days

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Primary Outcomes

Description: Time (in days) to clinical improvement is defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first within 30 days. The seven-category ordinal scale consisted of the following categories: Not hospitalized with resumption of normal activities Not hospitalized, but unable to resume normal activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both; Hospitalized, requiring ECMO, invasive mechanical ventilation, or both Death. These parameters will be evaluated daily during hospitalization.

Measure: Time (in days) to clinical improvement within 30 days after randomization

Time: within 30 days

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Secondary Outcomes

Measure: Mortality rate at D30

Time: At day30

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Measure: Time (in days) from randomization to death

Time: up to 30 days after randomization

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Measure: Number of days alive outside ICU within 30 days

Time: At day30

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

Time: At day30

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

Time: At day30

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Measure: Maximal oxygen rate within 30 days

Time: At day30

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

Time: at Day 7

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Measure: Number of days alive outside hospital within 30 days

Time: at Day 30

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

Time: at Day 30

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

Time: at Day 7

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

Time: up to 30 days after randomization

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Primary Outcomes

Description: Identify comorbidities predisposing for severe infection

Measure: Risk Factors for severe infection

Time: 2030

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Description: Immunological response to acute infection, focusing on initial innate host response and its associations to inflammatory enhancement, genetic factors and clinical course.

Measure: Immunulogical mechanisms

Time: 2030

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Description: prevalence and risk factors of long-lasting complication, in particular the development of post-infectious chronic fatigue

Measure: Long term outcome

Time: 2030

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Primary Outcomes

Measure: Changes in clinical critical treatment index

Time: day 7 from randomization

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Secondary Outcomes

Measure: Days of respirator treatment

Time: 3 months

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Measure: Improvement of clinical symptoms including duration of fever and respiratory need

Time: 3 months

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Measure: Mortality

Time: 3 months

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Measure: Marker of Immunological function -CD4+ and CD8+ T cell count

Time: 3 months

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Measure: C-reactive protein and leucocyte

Time: 3 months

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Measure: Cytokine profile

Time: 3 months

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Measure: Glomerular Filtration Rate

Time: 3 months

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Measure: Duration of hospitalization

Time: 3 months

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Primary Outcomes

Description: Number and severity of adverse events

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

Time: Up to 6 months

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

Measure: Phase 1: Rate of clearance of SARS-CoV-2

Time: Up to 6 months

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Description: Proportion of subjects who improved clinical symptoms related to lower respiratory tract infection, as measured by National Early Warning Score 2 (NEWS2) score.

Measure: Phase 1: Rate of clinical improvement

Time: Up to 6 months

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Description: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR. Negative results will need to be confirmed by a second negative result in the same sample type at least 24 hours after the first negative result.

Measure: Phase 2: Time to Clearance of SARS-CoV-2

Time: Up to 28 days

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Description: Time from the date of randomization to the first date of improved clinical symptoms related to lower respiratory tract infection. Improvement as measured by National Early Warning Score 2 (NEWS2) Score.

Measure: Phase 2: Time to Clinical Improvement by NEWS2 Score

Time: Up to 28 days

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Secondary Outcomes

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

Measure: Rate of Clearance of SARS-CoV-2

Time: Up to 6 months

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Description: Number and severity of adverse events

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

Time: up to 6 months

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

Measure: Overall Clinical Benefit by time to medical discharge

Time: up to 6 months

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

Measure: Overall Clinical Benefit by hospital utilization

Time: up to 6 months

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

Measure: Overall Clinical Benefit by measuring mortality rate

Time: up to 6 months

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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

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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

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Description: For ventilatory support subjects, the days with supplemental oxygen-free.

Measure: Supplemental oxygen-free days

Time: Up to 28 days

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Description: Proportion of subjects who need invasive or non-invasive ventilation

Measure: Proportion of subjects requiring ventilation

Time: Up to 28 days

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Primary Outcomes

Description: Mortality

Measure: Mortality

Time: 90 days following the enrollment

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Description: Th1/Th2/Th17/Treg balance, Type I Interferons and inflammation

Measure: Immune response - Plasma cytokine profile

Time: Through study completion (90 days following the enrollment)

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Description: T cells (CD3, CD4, CD8, PD1, FAS, CD45RO, CTLA4+, CXCR5, CXCR3, CCR6, CD69, CD95, HLA-DR) and B cells (CD3, CD19, CD27, IgD, CD69) with cell subtypes and memory/naive compartments (CD27, CD38, IgD, IgG1, IgG2, IgG3, CD20, CD24), NK cells (CD14, CD16, CD56, HLA-DR), monocytes (CD14, CD45, HLA-DR, PDL-1)

Measure: Immune response - Phenotype of circulating cells

Time: Through study completion (90 days following the enrollment)

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Secondary Outcomes

Description: Number of days in intensive care unit

Measure: Severity criteria - Duration of stay in intensive care unit

Time: 90 days following the enrollment

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Description: Number of days of hospitalization

Measure: Severity criteria - Duration of hospitalization stay

Time: 90 days following the enrollment

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Description: Number of days out of hospital

Measure: Severity criteria - Duration of period out of hospital

Time: 90 days following the enrollment

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Description: Number of days without mechanical ventilation (invasive/non-invasive)

Measure: Severity criteria - Duration without mechanical ventilation

Time: 90 days following the enrollment

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Description: Number of days not being ventilated

Measure: Severity criteria - Duration without ventilation

Time: 90 days following the enrollment

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Description: Number of days not being intubated

Measure: Severity criteria - Duration without intubation

Time: 90 days following the enrollment

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Description: Number of transfusions

Measure: Severity criteria - Number of transfusions

Time: 90 days following the enrollment

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Description: Number of days without cathecholamines

Measure: Severity criteria - Duration of the period without cathecholamines

Time: 90 days following the enrollment

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Description: Number of days without dialysis

Measure: Severity criteria - Duration of the period without dialysis

Time: 90 days following the enrollment

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Description: Sepsis-related Organ Failure Assessment (SOFA) Score

Measure: Severity criteria - SOFA

Time: Through study completion (90 days following the enrollment)

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Description: Lung Injury Score (LIS)

Measure: Severity criteria - LIS

Time: Through study completion (90 days following the enrollment)

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Description: SARS-Cov2 viral load will be measured in blood and in broncho-tracheal secretions

Measure: SARS-Cov2 viral load

Time: Through study completion (90 days following the enrollment)

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Description: Co-infections and acquired infections (bacterial or fungal) in intensive care unit, in particular based on an all-site positive PCR for EBV and/or CMV and/or HSV

Measure: Emergence of concomitant infections

Time: 90 days following the enrollment

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Description: T cells (CD3, CD4, CD8, PD1, FAS, CD45RO, CTLA4+, CXCR5, CXCR3, CCR6, CD69, CD95, HLA-DR) and B cells (CD3, CD19, CD27, IgD, CD69) with cell subtypes and memory/naive compartments (CD27, CD38, IgD, IgG1, IgG2, IgG3, CD20, CD24), NK cells (CD14, CD16, CD56, HLA-DR), monocytes (CD14, CD45, HLA-DR, PDL-1)

Measure: Emergence of concomitant infections - Phenotype of circulating cells

Time: Through study completion (90 days following the enrollment)

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Description: Heart rate variability

Measure: Stress physiological profile - Sympathetic tone

Time: Through study completion (90 days following the enrollment)

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Description: Core temperature

Measure: Stress physiological profile - Temperature

Time: Through study completion (90 days following the enrollment)

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Description: Quantity of glucocorticoids in the urine during 24 hours and at night

Measure: Stress physiological profile - Glucocorticoids

Time: Through study completion (90 days following the enrollment)

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Description: ACE Polymorphism

Measure: Angiotensin converting enzyme type II (ACE2) polymorphism - ACE

Time: At enrollment

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Description: Protein expression of ACE2 vs. ACE1 and angiotensin II chain proteins

Measure: Angiotensin converting enzyme type II (ACE2) polymorphism - ACE2/ACE1

Time: At enrollment

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Description: Diabete diagnosis

Measure: Comorbidities - diabetes

Time: At enrollment

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Description: Heart disease diagnosis

Measure: Comorbidities - Heart disease

Time: At enrollment

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Description: Organ failure diagnosis

Measure: Comorbidities - organ failure

Time: At enrollment

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Description: GABA level in blood and urine

Measure: Plasma concentrations of several metabolic pathways - GABA

Time: Through study completion (90 days following the enrollment)

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Description: Glucocorticoid level in blood and urine

Measure: Plasma concentrations of several metabolic pathways - Glucocorticoid

Time: Through study completion (90 days following the enrollment)

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Description: Tryptophan in blood and urine

Measure: Plasma concentrations of several metabolic pathways - Tryptophan

Time: Through study completion (90 days following the enrollment)

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Description: Serotonin level in blood and urine

Measure: Plasma concentrations of several metabolic pathways - Serotonin

Time: Through study completion (90 days following the enrollment)

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Description: Dopamin level in blood and urine

Measure: Plasma concentrations of several metabolic pathways - Dopamin

Time: Through study completion (90 days following the enrollment)

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Description: Catecholamines level in blood and urine

Measure: Plasma concentrations of several metabolic pathways - Cathecholamines

Time: Through study completion (90 days following the enrollment)

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Description: Arachidonic acid derivatives level in blood and urine

Measure: Plasma concentrations of several metabolic pathways - Arachidonic acid derivatives

Time: Through study completion (90 days following the enrollment)

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Description: Endocannabinoids level in blood and urine

Measure: Plasma concentrations of several metabolic pathways - Endocannabinoids

Time: Through study completion (90 days following the enrollment)

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Primary Outcomes

Description: Clinical change is defined as 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19: 0 - No clinical or virological evidence of infection; 1 - No limitation of activities; 2 - Limitation of activities; 3 - Hospitalized, no oxygen therapy; 4 - Oxygen by mask or nasal prongs; 5 - Non-invasive ventilation or high-flow oxygen; 6 - Intubation and mechanical ventilation; 7 - Ventilation + additional organ support - pressors, renal replacement therapy, extracorporeal membrane oxygenation; 8 - Death.

Measure: Time to clinical change

Time: 28 days

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Secondary Outcomes

Measure: Percent of serious adverse events and premature discontinuation of treatment.

Time: 28 days

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Description: Percent of patients with a 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19.

Measure: Percent of patients with clinical improvement.

Time: 28 days

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Measure: Length of hospitalization.

Time: 28 days

---

Measure: All-cause mortality.

Time: 28 days

---

Measure: Percent of supplemental oxygen use.

Time: 28 days

---

Measure: Supplemental oxygen-free days.

Time: 28 days

---

Measure: Percent of mechanical ventilation use.

Time: 28 days

---

Measure: Ventilator-free days.

Time: 28 days

---

Measure: Percent of ICU admissions.

Time: 28 days

---

Measure: ICU-free days.

Time: 28 days

---

Measure: Percent of 50% decrease in C-reactive protein (CRP) levels

Time: Up to 28 days

---

Measure: Time to virologic response, defined as no detection of SARS-CoV-2 in a PCR test.

Time: 28 days

---

Primary Outcomes

Description: Time to clinical improvement: defined as time from inhaled Ibuprofen first dose to an improvement of three points from the status on a seven-category ordinary scale

Measure: Change in the scale of ordinary COVID results at 7, 14 and 28 days in patients with acute respiratory infection, induced by SARS-CoV-2, treated with inhaled Ibuprofen.

Time: 7, 14 and 28 days

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Description: Negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart

Measure: Change to Negativization of the swab to the following treatment points on day 7, day 14, 21 and 28 after treatment with inhaled Ibuprofen.

Time: 7, 14 and 28 days

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Secondary Outcomes

Measure: Chage in length of Hospital stay

Time: 28 days

---

Measure: Chage in duration of ventilation

Time: 28 days

---

Measure: Chage in length of Critical Care stay

Time: 28 days

---

Description: NEWS2 score 20 points is the maximum and indicates that the patient needs emergent assessment by a clinical team or critical care team and usually transfer to higher level of care.

Measure: Average score of National Early Warning (NEWS2) between days 1, 7, 14 and 28.

Time: 1, 7, 14 and 28

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Description: qSOFA, score for sepsis, a maximum value of 3 indicates high risk qSOFA Scores 2-3 are associated with a 3- to 14-fold increase in in-hospital mortality. Assess for evidence of organ dysfunction with blood testing including serum lactate and calculation of the full SOFA Score. Patients meeting these qSOFA criteria should have infection considered even if it was previously not.

Measure: Average change in quick sepsis-related organ failure assessment score (qSOFA) score between day 1, 7, 14 and 28.

Time: 1, 7, 14 and 28 days

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Measure: Time from first dose to conversion to normal or mild pneumonia

Time: 28 days

---

Measure: Antibiotic requirement

Time: 28 days

---

Measure: Glucocorticoids requirement

Time: 28 days

---

Measure: Incidence of adverse event

Time: 28 days

---

Measure: Incidence of serious adverse event

Time: 28 days

---

Measure: Number of deaths from any cause at 28 days

Time: 28 days

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Measure: Lymphocyte count

Time: 28 days

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Primary Outcomes

Description: Vincent and co-authors (2011) proposed the Pulmonary Rehabilitation Adapted Index of Self-Efficacy (PRAISE). The PRAISE tool is composed by a total of 15 items, combining 10 items from the General Self-Efficacy Scale (GSE) by Schwarzer and Jerusalem (1995), and 5 new specific items related to Pulmonary Rehabilitation. Each item is scored from 1 to 4 with a total range from 15 to 60, with higher scores indicating higher levels of self-efficacy. This study applies the Portuguese PRAISE version by Santos CD and co-authors (2019).

Measure: Patient's self-efficacy

Time: 3 days

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Secondary Outcomes

Description: Patients were questioned if they were engaging on a daily routine of respiratory exercises by their initiative while isolated at home COVID-19 outbreak. The answer was registered as yes/no.

Measure: Respiratory exercises

Time: 3 days

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Description: Patients were questioned if they managed to preserve a daily period to practice physical activity while isolated at home during COVID-19 outbreak. The answer was recorded as yes/no. In case of a positive answer, information concerning available equipment and exercise protocol adopted at patient's home environment was also collected.

Measure: Physical activity

Time: 3 days

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Other Outcomes

Description: Number of Pulmonary Rehabilitation hospital sessions completed as outpatient, according to Hospital Pulido Valente information system

Measure: Treatment sessions completed

Time: 3 days

---

Description: Number of Pulmonary Rehabilitation sessions planned per week, according to Hospital Pulido Valente information system

Measure: Treatment weekly frequency

Time: 3 days

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Primary Outcomes

Description: To determine whether the addition of the intervention, compared to standard care, changes the clinical health score of a participant on the following scale; Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Death;

Measure: 7-Point National Institute of Health Clinical Health Score

Time: 28 Days

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Secondary Outcomes

Description: To determine whether the addition of the intervention, compared to standard care, changes the clinical health score of a participant on the following scale; Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Death;

Measure: 7-Point National Institute of Health Clinical Health Score

Time: 15 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality

Measure: Mortality

Time: 28 Days

---

Description: To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality

Measure: Mortality

Time: 90 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission

Measure: Intensive Care Unit Admission

Time: 28 Days

---

Description: To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission

Measure: Intensive Care Unit Admission

Time: 90 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes the number of days total, of intensive care unit admission

Measure: Intensive Care Unit Admission

Time: 90 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure

Measure: Respiratory Failure

Time: 90 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis

Measure: Dialysis Requirement

Time: 90 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days

Measure: Hospitalisation Days

Time: 28 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days

Measure: Hospitalisation Days

Time: 90 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes need for ventilation

Measure: Ventilator-Free Days

Time: 28 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes need for dialysis

Measure: Dialysis Days

Time: 28 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes risk of acute kidney injury, based on the idney Disease: Improving Global Outcomes definition

Measure: Acute Kidney Injury

Time: 28 Days

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Description: To determine whether the addition of the intervention, compared to standard care, changes risk of hypotension requiring vasopressors

Measure: Hypotension Requiring Vasopressors

Time: 90 Days

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Primary Outcomes

Description: Time to deterioration measured by need for NIV, HFNC or intubation

Measure: Time to deterioration

Time: 14 Days

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Secondary Outcomes

Description: Time to non-invasive ventilation

Measure: Time to NIV

Time: 14 Days

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Description: Time to high flow nasal cannula

Measure: Time to HFNC

Time: 14 Days

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Description: Time to intubation

Measure: Time to intubation

Time: 14 days

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Description: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93%

Measure: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93%

Time: 14 days

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Other Outcomes

Description: Need for supplemental oxygen

Measure: Need for supplemental oxygen

Time: 14 days

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Description: Change in viral load

Measure: Change in viral load

Time: 30 days

---

Description: Duration of the Hospital Length of Stay (LOS)

Measure: Duration of the Hospital Length of Stay (LOS)

Time: 14 days

---

Description: Mortality rate at Day 30

Measure: Mortality rate at Day 30

Time: 30 days

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Primary Outcomes

Description: Value of 6 or greeter on WHO CoVid-19 scale, indicating of a critical form of CoVid-19.

Measure: Percentage of patients who reached, during their hospitalization, a value greater than or equal to 6 on the WHO CoVid-19 infection progression scale

Time: up to 28 days (during hospitalisation)

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Secondary Outcomes

Description: Radiological damage (extension of ground-glass) could be a predictive factor.

Measure: Determined potential predictive factors of critic form in patients with chronic lung diseases

Time: up to 28 days (during hospitalisation)

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Description: intra-hospital death, intra-ICU death

Measure: Determined percentage of death

Time: up to 28 days (during hospitalisation)

---

Description: in days (or duration at a different flow rate compared to long-term home oxygen therapy prior to hospitalization)

Measure: Determined duration of oxygen therapy

Time: up to 28 days (during hospitalisation)

---

Description: in days for patients with chronic respiratory disease between the date of admission and the date of discharge. Patients who died during hospitalization will be assigned the highest cohort value.

Measure: Determined duration of hospitalization

Time: up to 28 days (during hospitalisation)

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Description: values will be measured at D3, D7 and D14 in each of the groups. Patients who do not reach D7 and D14 will have the last postponement

Measure: Determine mean values of the WHO CoVid-19 infection progression scale measured

Time: up to 28 days (during hospitalisation)

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Primary Outcomes

Description: Time to deterioration as measured by any one of the following: need for non-invasive ventilation need for high flow nasal cannula (HFNC) or need for intubation Death from any cause

Measure: Time to deterioration

Time: up to 14 days

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Secondary Outcomes

Description: Time to patient having stable oxygen saturation (SpO2) of greater than 92% for longer than 3 hr on room air

Measure: Time to stable oxygen saturation

Time: up to 14 days

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Other Outcomes

Description: Treatment Emergent Adverse Events and SAEs - safety evaluation for 30 days after last inhalation treatment

Measure: Treatment Emergent Adverse Events and SAEs

Time: 30 days after last inhalation treatment

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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.

Measure: Survival without needs of ventilator utilization at day 14

Time: day 14

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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 at day 7 and 14

Time: day 7 and day 14

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Description: Overall survival

Measure: Overall survival at 14, 28, 60 and 90 days

Time: 14, 28, 60 and 90 days

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Description: Cumulative incidence of discharge alive

Measure: Cumulative incidence of discharge alive at 14 and 28 days

Time: 14 and 28 days

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Description: Survival without needs of mechanical ventilation at day 1. 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 mechanical ventilation at day 1

Time: day 1

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Description: Cumulative incidence of oxygen supply independency

Measure: Cumulative incidence of oxygen supply independency at 14 and 28 days

Time: 14 and 28 days

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Primary Outcomes

Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 14.

Time: 14 days

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Secondary Outcomes

Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 28

Time: 28 days

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Description: ICU admission, mechanical ventilation, death or consent withdrawal

Measure: Time to treatment failure

Time: 28 days

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Measure: Overall survival at days 14 and 28

Time: 14 and 28 days

---

Measure: Cumulative incidence of ICU admission rate at days 14 and 28

Time: 14 and 28 days

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Measure: Cumulative incidence of mechanical ventilation at days 14 and 28

Time: 14 and 28 days

---

Measure: Duration of hospital stay

Time: 28 days

---

Measure: Duration of ICU stay

Time: 28 days

---

Measure: Duration of mechanical ventilation

Time: 28 days

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Measure: Duration of non-invasive ventilation

Time: 28 days

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Measure: Secondary hemophagocytic syndrome rate

Time: 28 days

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Measure: Cumulative incidence nosocomial infection rate at days 14 and 28

Time: 14 and 28 days

---

Measure: Incidence of discontinuation of oxygen supplementation at days 14 and 28

Time: 14 and 28 days

---

Measure: Rate of grade 1-2 and 3-5 emerging adverse events at day 28

Time: 28 days

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Measure: Cumulative dose of methylprednisolone at days 14 and 28

Time: 14 and 28 days

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Measure: Change in PaO2/FiO2 ratio from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in interleukin 6 levels [pg/mL] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in d-dimer levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in fibrinogen levels [mg/dL] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in ferritin levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in C reactive protein levels [mg/L] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in alanine aminotransferase [U/L] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in aspartate aminotransferase [U/L] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in creatinine levels [mg/dL] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in glucose levels [mg/dL] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in hemoglobin levels [g/dL] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in platelet count [x10ˆ3/mmˆ3] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in absolute neutrophil count [x10ˆ3/mmˆ3] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in absolute neutrophil count [/mmˆ3] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in absolute lymphocyte count [/mmˆ3] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in prothrombin time ratio from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in partial thromboplastin time ratio from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in bilirubin [mg/dl] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in lactate dehydrogenase [U/L] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in CPK-MB [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in troponin [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in von Willebrand factor antigen level (VWF:Ag) [%] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in von Willebrand factor activity (ristocetin cofactor) [%] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in ADAMTS-13 [%] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in von Willebrand multimeters from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in plasminogen activator inhibitor-1 levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

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Measure: Change in E-selectin levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in P-selectin levels [ng/mL] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in endothelin [fmol/mL] from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in circulating microparticles from baseline to days 14 and 28

Time: 14 and 28 days

---

Measure: Change in thromboelastography from baseline to days 14 and 28

Time: 14 and 28 days

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Primary Outcomes

Description: Accuracy of rPPG heart rate compared to conventional vital sign monitor heart rate readings. Comparison of each paired reading.

Measure: Accuracy of rPPG heart rate

Time: immediate; paired reading

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Description: Accuracy of rPPG oxygen saturation compared to conventional vital sign monitor oxygen saturation readings. Comparison of discrepancy within each paired reading set.

Measure: Accuracy of rPPG oxygen saturation

Time: immediate; paired reading

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Description: Accuracy of rPPG respiratory rate compared to manual counting of respiratory rate over 60 seconds. Comparison of discrepancy within each paired reading set.

Measure: Accuracy of rPPG respiratory rate

Time: immediate; paired reading

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Secondary Outcomes

Description: Comparison of rPPG heart rate results obtained on a given patient on serial readings within 2 minutes of each other.

Measure: Reproducibility of rPPG heart rate readings

Time: 2-5 minutes

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Description: Comparison of rPPG oxygen saturation results obtained on a given patient on serial readings within 2 minutes of each other.

Measure: Reproducibility of rPPG oxygen saturation readings

Time: 2-5 minutes

---

Description: Comparison of rPPG respiratory rate results obtained on a given patient on serial readings within 2 minutes of each other.

Measure: Reproducibility of rPPG respiratory rate readings

Time: 2-5 minutes

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Other Outcomes

Description: Analysis of accuracy of rPPG vital sign readings when stratified by oxygen saturation per conventional monitors stratified as follows: 95-100%; 90-94%; 85-89%; Less than 85%

Measure: Accuracy of rPPG readings by oxygen saturation level

Time: immediate; stratified analysis

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Description: Analysis of accuracy of rPPG vital sign readings when stratified by skin colour per the Fitzpatrick scale

Measure: Accuracy of rPPG readings by skin colour

Time: immediate; stratified analysis

---

Description: Analysis of accuracy of rPPG vital sign readings when stratified for gender

Measure: Accuracy of rPPG readings by gender

Time: immediate; stratified analysis

---

Description: Analysis of accuracy of rPPG vital sign readings when stratified by age group

Measure: Accuracy of rPPG readings by age

Time: immediate; stratified analysis

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Description: Analysis of accuracy of rPPG vital sign readings when stratified for COVID, respiratory conditions, cardiac conditions and vascular conditions.

Measure: Accuracy of rPPG readings by comorbidity

Time: immediate; stratified analysis

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Primary Outcomes

Description: The variation of regional compliance, calculated by electrical impedance

Measure: Regional Compliance Variation

Time: From FOB/BAL to 6 hours later

---

Secondary Outcomes

Description: The variation of regional resistance, calculated by electrical impedance

Measure: Regional Resistance Variation

Time: From FOB/BAL to 6 hours later

---

Description: Relation between regional compliance variation and FOB duration

Measure: Regional Compliance and FOB duration

Time: From FOB/BAL to 6 hours later

---

Description: Relation between regional compliance variation and PaO2 variation

Measure: Regional Compliance and PaO2

Time: From FOB/BAL to 6 hours later

---

Description: Relation between atelectasis impedance-detected areas and BAL flooded impedance-detected areas

Measure: Atelectasis areas and BAL flooded areas

Time: From FOB/BAL to 6 hours later

---

Description: Variation of PaO2 and PaO2/FiO2 ratio post FOB/BAL

Measure: PaO2 and PaO2/FiO2 ratio

Time: From FOB/BAL to 6 hours later

---

Description: Variation of PaCO2 post FOB/BAL

Measure: PaCO2

Time: From FOB/BAL to 6 hours later

---

Description: Relation between the endotracheal tube/fiberscope size ratio and gas exchanges

Measure: Endotracheal tube size and Fiberscope size

Time: From FOB/BAL to 6 hours later

---

Description: Heart rate (HR), Blood Pressure (BP)

Measure: Hemodynamic variations

Time: From FOB/BAL to 6 hours later

---

Primary Outcomes

Description: spatiotemporal spread of COVID-19 patient in our hospital

Measure: spatiotemporal spread

Time: February 1, 2020 to September 30, 2020

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Secondary Outcomes

Description: risk classification score of each patients with clinical and analytical variables

Measure: classification score

Time: February 1, 2020 to September 30, 2020

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Primary Outcomes

Description: respiratory muscle training appears to impact functionality

Measure: impact on functionality

Time: 14 days

---

Primary Outcomes

Description: Clinical safety will be assessed by incidence of Serious Adverse Events (SAEs)

Measure: incidence of Serious Adverse Events

Time: 30 days

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Secondary Outcomes

Description: Time to fever resolution

Measure: fever resolution

Time: Baseline to 30 days

---

Description: Number of patients requiring admission to ICU

Measure: ICU admission

Time: Baseline to 30 days

---

Description: Time until patient no longer requires supportive oxygen

Measure: Oxygen support

Time: Baseline to 30 days

---

Description: b.d. Stable room air saturation of 93% and above or returning to baseline saturation, whichever is lower

Measure: Stable room air saturation

Time: Baseline to 30 days

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Primary Outcomes

Description: 28-day all-cause mortality

Measure: 28-day all-cause mortality

Time: Day 28

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Secondary Outcomes

Description: Time to 7-category ordinal scale of clinical status improvement (T7COSCSI)

Measure: Time to 7-category ordinal scale of clinical status improvement (T7COSCSI)

Time: Up to 60 days

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Description: Ventilator-free days (VFDs) within 28 days

Measure: Ventilator-free days (VFDs) within 28 days

Time: Up to 28 days

---

Description: Organ failure-free days (OFFD)

Measure: Organ failure-free days (OFFD)

Time: Up to 60 days

---

Description: Intensive care unit length of stay (ICU LOS)

Measure: Intensive care unit length of stay (ICU LOS)

Time: Up to 60 days

---

Description: Hospital length of stay (HLOS)

Measure: Hospital length of stay (HLOS)

Time: Up to 60 days

---

Description: In-hospital all-cause mortality (IHACM)

Measure: In-hospital all-cause mortality (IHACM)

Time: Up to 60 days

---

Description: 60-day all-cause mortality (60DACM)

Measure: 60-day all-cause mortality (60DACM)

Time: Up to 60 days

---

Description: Time to oxygenation improvement (TOI)

Measure: Time to oxygenation improvement (TOI)

Time: Up to 60 days

---

Description: Duration of supplemental oxygen (DSO)

Measure: Duration of supplemental oxygen (DSO)

Time: Up to 60 days

---

Description: Chest radiographic improvement (CRI)

Measure: Chest radiographic improvement (CRI)

Time: Up to 60 days

---

Description: Time to National Early Warning Score 2 improvement (TNEWS2I)

Measure: Time to National Early Warning Score 2 improvement (TNEWS2I)

Time: Up to 60 days

---

Description: Treatment-emergent adverse events (TEAEs)

Measure: Treatment-emergent adverse events (TEAEs)

Time: Up to 60 days

---

Description: Plasma siltuximab concentrations (PSCs)

Measure: Plasma siltuximab concentrations (PSCs)

Time: Up to 60 days

---

Description: Anti-siltuximab antibodies (ASA)

Measure: Anti-siltuximab antibodies (ASA)

Time: Up to 60 days

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Primary Outcomes

Description: Change in Forced Vital Capacity (FVC) at 180 days as compared to baseline. Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from your lungs after taking the deepest breath possible, as measured by spirometry.

Measure: Change in Forced Vital Capacity (FVC)

Time: Baseline and 180 days

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Secondary Outcomes

Description: Death within 90 days and 180 days from enrollment due to a respiratory cause

Measure: Number of deaths due to respiratory cause

Time: within 90-180 days

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Description: Quantitative Change in chest CT visual score graded by blinded chest radiologists. Data driven texture analysis (DTA) is a patented deep learning method to quantify lung fibrosis. DTA score is reported in percentage ranging from 0% to 100%. A minimally clinical important difference when comparing CT scans from the same subject is 4%. A higher percentage suggests worsening lung injury.

Measure: Chest CT visual score

Time: 180 days

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Description: The Saint George's Respiratory Questionnaire (SGRQ) is a self-reported disease-specific, health-related quality of life (QOL) questionnaire. 50-item instrument. Scores range from 0 to 100, with higher scores indicating more limitations.

Measure: St. George's Respiratory Questionnaire (SGRQ)

Time: Day 90

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Description: The Saint George's Respiratory Questionnaire (SGRQ) is a self-reported disease-specific, health-related quality of life (QOL) questionnaire. 50-item instrument. Scores range from 0 to 100, with higher scores indicating more limitations.

Measure: St. George's Respiratory Questionnaire (SGRQ)

Time: Day 180

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Description: The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a self-administered, ILD-specific measure of health-related quality of life, comprising 15 items with three domains (Psychological (KBILD-P), Breathlessness and activities (KBILD-B), and Chest symptoms (KBILD-C)) combined in a total score (KBILD-T). The KBILD domain and total score ranges are 0-100; 100 represents best health status.

Measure: King's Brief Interstitial Lung Disease (KBILD)

Time: Day 90

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Description: The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a self-administered, ILD-specific measure of health-related quality of life, comprising 15 items with three domains (Psychological (KBILD-P), Breathlessness and activities (KBILD-B), and Chest symptoms (KBILD-C)) combined in a total score (KBILD-T). The KBILD domain and total score ranges are 0-100; 100 represents best health status.

Measure: King's Brief ILD (KBILD)

Time: Day 180

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Description: The LCQ is a 19 item questionnaire that assesses cough-related QOL. It has 3 domains (physical, psychological and social). The domain scores range from 1-7 and total score range is 3-21 with a higher score indicating a better quality of life.

Measure: Leicester Cough Questionnaire (LCQ)

Time: Day 90

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Description: The LCQ is a 19 item questionnaire that assesses cough-related QOL. It has 3 domains (physical, psychological and social). The domain scores range from 1-7 and total score range is 3-21 with a higher score indicating a better quality of life.

Measure: Leicester Cough Questionnaire

Time: Day 180

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Description: The (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status. Scores range from 0 - 100, with higher scores indicating less disability.

Measure: Short Form (SF) 36 Health Survey

Time: Day 90

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Description: The (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status. Scores range from 0 - 100, with higher scores indicating less disability.

Measure: SF 36 Health Survey

Time: Day 180

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Description: Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression. 14-items scale with responses scored from 0-3, scores for each subscale from 0 (normal) to 21 (severe symptoms). Scores for the entire scale is 0 to 42, with higher score indicating more distress.

Measure: Hospital Anxiety and Depression Scale (HADS)

Time: Day 90

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Description: Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression. 14-items scale with responses scored from 0-3, scores for each subscale from 0 (normal) to 21 (severe symptoms). Scores for the entire scale is 0 to 42, with higher score indicating more distress.

Measure: Hospital Anxiety and Depression Scale (HADS)

Time: Day 180

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Description: Number of participants with Increase in liver transaminases

Measure: Number of participants with Increase in liver transaminases (AST and ALT) > 3 times the upper limit of normal

Time: day 90

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Description: Number of participants with Increase in liver transaminases

Measure: Number of participants with Increase in liver transaminases (AST and ALT) > 3 times the upper limit of normal

Time: day 180

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Description: Number of participants with Thrombotic events: venous or arterial thrombosis

Measure: Number of participants with Thrombotic events

Time: day 90

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Description: Number of participants with Thrombotic events: venous or arterial thrombosis

Measure: Number of participants with Thrombotic events

Time: day 180

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Description: Number of participants with 10% weight loss

Measure: Number of participants with 10% weight loss over 90 days

Time: day 90

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Description: Number of participants with 10% weight loss

Measure: Number of participants with 10% weight loss over 90 days

Time: day 180

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Description: Number of participants with Nausea/emesis/diarrhea not responsive to anti-emetics and anti-motility agents

Measure: Number of participants with GI events

Time: day 90

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Description: Number of participants with Nausea/emesis/diarrhea not responsive to anti-emetics and anti-motility agents

Measure: Number of participants with GI events

Time: day 180

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