COVID-19 Respiratory Outcomes Registry

Completed

• Conditions: Covid19
• Interventions: Other: Questionnaires and Patient Reported Outcomes (PROs); Diagnostic Test: Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR); Genetic: Blood Samples for Biomarkers; Diagnostic Test: High Resolution Computed Tomography; Diagnostic Test: Physical Exam and Vital Signs; Diagnostic Test: Medical Research Council Sum Score; Diagnostic Test: Hand Grip Strength; Diagnostic Test: Spirometry; Diagnostic Test: Diffusing Capacity of Carbon Monoxide; Diagnostic Test: 6 Minute Walk Test; Diagnostic Test: Sit to Stand (STS) Measurement

• Registration Number: NCT05074875
• Lead Sponsor: Weill Medical College of Cornell University

Brief Summary

This is a 48-week, observational study looking to see if the inflammatory process of hypoxemic respiratory failure associated with COVID-19 leads to progressive pulmonary fibrosis. Inpatient, as well as outpatient adults with recent COVID-19 hospitalization will be recruited. Data from hospitalization will be collected and subjects will return to the center for follow-up visits. Subjects will undergo the following procedures: High Resolution Computed Tomography (HRCT) of the chest, Pulmonary Function Tests (PFT), Muscle Strength Measurement, and blood draw for biomolecular data such as biomarkers found in ribonucleic acid (RNA), deoxyribonucleic acid (DNA), serum, and plasma. Quality of Life (QoL) measurements will also be collected through the study.

Detailed Description

This is a multi-center, observational, and prospective study collecting data on subjects who were hospitalized with hypoxemic respiratory failure associated with COVID-19 or patients who have evidence of an outpatient COVID-19 infection that have been treated with supplemental oxygen.

A total of approximately 300 subjects will be enrolled in the study. Subjects will be enrolled into one of 3 cohorts.

Cohort 1: Inpatient Enrollment: Subjects enrolled while hospitalized for COVID-19, prior to discharge.

Cohort 2: Outpatient Enrollment: Subjects enrolled up to 4 weeks after discharge from hospitalization for COVID-19 or 4 weeks post their outpatient COVID -19 infection.

Cohort 3: Outpatient Enrollment: Subjects enrolled between 6 and 24 weeks after discharge from hospitalization for COVID-19 or 6 and 24 weeks post their outpatient COVID -19 infection. Cohort 3 will be sub-divided into 3a and 3b depending on the timepoint of enrollment.

After signing the Informed Consent Form, the screening visit will be performed. Screening and enrollment can occur at Visit 0 (inpatient) or Visit 1 (outpatient). Following completion of Visit 0 or 1 the subjects' data will be assessed by the investigator to confirm eligibility and a decision will be made if the patient is to be enrolled. If not the reason for non-enrollment will be listed in the trial log.

Each subject will either have a total of 4 or 5 visits, depending on if subjects complete enrollment while still admitted to the hospital (Visit 0) or at Visit 1. At weeks 4, 24, 36, 48, all subjects will complete questionnaires, have physical exams, spirometry test with DLCO, HRCTs, 6MWTs, blood draws, and review of medical history since the previous visit.

The primary analysis of this study will be performed once the last enrolled subject reaches Week 48. At that time, there will be a data-base lock. Unless otherwise noted, Visit 1 is treated as baseline measurement. In addition, for patients enrolled at discharge, a second set of analysis will be performed treating Visit 0 as baseline for the measurements collected at Visit 0.

Aim 1: To identify whether the trajectory of COVID-19 associated respiratory failure results in progressive pulmonary fibrosis with clinical features or biomolecular changes.

Aim 2: To identify biomarkers that may indicate those patients at risk for developing a chronic fibrotic HRCT pattern that may go on to progression.

Study Timeline

• Study Start: 2021-01-15
• Study First Submitted: 2021-04-06
• Study First Submitted QC: 2021-10-08
• Study First Posted: 2021-10-12
• Primary Completion: 2023-05-09
• Study Completion: 2023-05-09
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-25
• Last Update Posted: 2023-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

1. Written Informed Consent consistent with International Conference on Harmonization Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study
2. Male or female ≥ 18 years of age at the time of consent
3. SARS-CoV-2 positive confirmed by a positive serology or PCR or antigen test
4. COVID-19 induced hypoxemia or reduced oxygen saturation requiring treatment with supplemental oxygen.
5. COVID-19 hospital discharge date or outpatient COVID-19 infection within 24 weeks of enrollment

Exclusion Criteria

1. Diagnosed with Fibrotic Interstitial Lung Disease (ILD) prior to COVID-19 infection.
2. Prior treatment with an antifibrotic agent, including nintedanib or pirfenidone
3. Pregnant women or women planning on becoming pregnant in the next 12 months
4. Patients planned for discharge from the hospital to hospice
5. Patients with significant cognitive impairment

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cohort 1	High Resolution Computed Tomography	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 1	6 Minute Walk Test	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 1	Blood Samples for Biomarkers	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 1	Hand Grip Strength	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 1	Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR)	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 2	Questionnaires and Patient Reported Outcomes (PROs)	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 2	Blood Samples for Biomarkers	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 1	Questionnaires and Patient Reported Outcomes (PROs)	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 1	Physical Exam and Vital Signs	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 2	High Resolution Computed Tomography	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 2	Spirometry	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 3a	Blood Samples for Biomarkers	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 3a	Diffusing Capacity of Carbon Monoxide	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 1	Medical Research Council Sum Score	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 2	Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR)	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 2	Physical Exam and Vital Signs	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 2	Diffusing Capacity of Carbon Monoxide	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 3a	Spirometry	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 3b	Blood Samples for Biomarkers	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 3b	High Resolution Computed Tomography	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 1	Spirometry	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 1	Diffusing Capacity of Carbon Monoxide	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 1	Sit to Stand (STS) Measurement	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 1 subjects will undergo Visit 0 after informed consent is obtained. Eligible subjects will return for follow-up at Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks
Cohort 2	Medical Research Council Sum Score	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 3a	Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR)	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 3a	High Resolution Computed Tomography	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 3a	Hand Grip Strength	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 2	Hand Grip Strength	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 2	6 Minute Walk Test	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 2	Sit to Stand (STS) Measurement	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohort 2 subjects will undergo Visit 1, within 4 (+/- 2) weeks of hospital discharge or outpatient infection, after informed consent is obtained. Eligible subjects will return for follow-up Visits 2, 3, and 4, at weeks 24, 36, and 48 weeks.
Cohort 3a	Questionnaires and Patient Reported Outcomes (PROs)	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 3a	Physical Exam and Vital Signs	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 3a	Medical Research Council Sum Score	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 3a	Sit to Stand (STS) Measurement	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 3b	Questionnaires and Patient Reported Outcomes (PROs)	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 3b	Medical Research Council Sum Score	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 3b	Diffusing Capacity of Carbon Monoxide	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 3a	6 Minute Walk Test	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled within ≤ 12 weeks of hospital discharge or outpatient COVID- 19 infection will undergo their first study visit at Visit 1 (Weeks 6-12).
Cohort 3b	Nasal Swab COVID-19 reverse transcription polymerase chain reaction test (RT-PCR)	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 3b	Physical Exam and Vital Signs	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 3b	Hand Grip Strength	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 3b	Spirometry	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 3b	6 Minute Walk Test	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.
Cohort 3b	Sit to Stand (STS) Measurement	Subjects with a diagnosis of hypoxemic respiratory failure associated with COVID-19 who meet the inclusion and exclusion criteria will be eligible for participation in this study. Cohorts 3a and 3b subjects will undergo their first study visit between 6 and 24 weeks of hospital discharge or outpatient infection, after informed consent is obtained. Participants should not be scheduled for chest HRCTs less than 12 weeks apart, however all subjects should have an HRCT done at Week 24 for analysis purposes. To prevent scheduling of HRCTs within less than 12 weeks. Subjects enrolled ≥ 12 weeks from hospital discharge or outpatient COVID- 19 infection will undergo their first visit within 4 weeks before week 24. Subjects that are enrolled into Cohort 3 will be followed until Week 72.

Primary Outcome Measures

Name	Time	Method
Change in fibrotic and non-fibrotic interstitial opacities on chest HRCT at 48 weeks after hospitalization for COVID-19 or outpatient COVID-19 infections which require treatment with supplemental oxygen	48 Weeks	Categorized after exploratory analysis as improved, stable or worsened fibrotic changes seen on chest HRCT.

Secondary Outcome Measures

Name	Time	Method
Changes from baseline and evidence of disease progression seen on high resolution computed tomography	72 Weeks	Percentage of subjects with evidence of disease progression by HRCT changes from baseline to 24, 36, 48 and 72 weeks.
Changes from baseline and evidence of disease progression seen on pulmonary function testing	72 weeks	Relative change in Diffusing Capacity of Carbon Monoxide percent predicted (DLCO) from baseline to 24, 36, 48 and 72 weeks.
Changes from baseline and evidence of disease progression via 6 Minute Walk Test	72 weeks	Change from baseline 6 Minute Walk Test (6MWT) distance (feet) from baseline to 24, 36, 48 and 72 weeks.
Changes from baseline and evidence of disease progression by Hand Grip Strength	72 weeks	Change in Hand Grip Strength value (kg) via hand dynamometer from baseline to 24, 36, 48 and 72 weeks.
Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes. St. George's Respiratory Questionnaire (SGRQ)	72 weeks	Change from baseline Quality of Life (QoL) questionnaires from baseline to 24, 36, 48 and 72 weeks.; St. George's Respiratory Questionnaire (SGRQ); Patients respond to different prompts by checking off the amount of respiratory symptom occurrences.; Other prompts require true or false responses.
Changes from baseline and evidence of disease progression on pulmonary function testing	72 weeks	Relative change in Forced Vital Capacity percent predicted (FVC) from baseline to 24, 36, 48 and 72 weeks.
Changes from baseline and evidence of disease progression see on pulmonary function testing	72 weeks	Change in Maximum Inspiratory (PI Max) and Maximum Expiratory (PE Max) \[cm H2O\] from baseline to 24, 36, 48 and 72 weeks.
Change in pre- and post- six minute walk test Borg Scale Dyspnea score from baseline and at 12, 24, and 48 weeks.	72 weeks	The top of the scale, "0 or nothing at all," means no breathlessness at all. The bottom of the scale, "10 or maximal," means the most severe breathlessness that you have ever experienced or could imagine experiencing from baseline to 24, 36, 48 and 72 weeks.
Change in pre- and post- six minute walk test Borg Scale Fatigue score from baseline and at 12, 24, and 48 weeks.	72 weeks	The top of the scale, "0 or nothing at all," means no fatigue at all. The bottom of the scale, "10 or maximal," means the most severe fatigue that you have ever experienced or could imagine experiencing from baseline to 24, 36, 48 and 72 weeks.
Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes. EuroQol-5D (EQ-5D)	72 weeks	Change from baseline Quality of Life (QoL) questionnaires from baseline to 24, 36, 48 and 72 weeks.; EuroQol-5D (EQ-5D) capture health status by asking 5 questions and by using a visual analog scale (0-100)
Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes- PROMIS-29 + 2 Profile	72 weeks	Change from baseline Quality of Life (QoL) questionnaires from baseline to 24, 36, 48 and 72 weeks.; PROMIS-29 + 2 Profile; 31- item patient reported outcome to measure physical function, anxiety, depression, fatigue, sleep disturbance, social roles, cognition, and pain in adults.
Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes. Generalized Anxiety 7-Item (GAD-7)	72 weeks	Change from baseline Quality of Life (QoL) questionnaires from baseline to 24, 36, 48 and 72 weeks.; Generalized Anxiety 7-Item (GAD-7) is a 7-item tool used to measure anxiety in patients. Each question is answered on a scale of 0-3; 0- Not at all; 1. Several Days; 2. More than half the days; 3. Nearly every day; Score indications: 0-4: minimal anxiety 5-9: mild anxiety 10-14: moderate anxiety 15-21: severe anxiety
Examine the effects of COVID-19 on the presence of molecular biomarkers associated with Interstitial Lung Disease	72 weeks	Biomarkers prognostic for progression in PF patients incl. Soluble intercellular adhesion molecule-1 (sICAM-1), Surfactant protein D (SP-D), cancer antigen 125 (CA-125), cancer antigen (CA19-9), matrix metalloproteinase7 (MMP7), Krebs von den Lungen-6 (KL-6); Biomarkers elevated in PF (vs age-matched controls) incl. cancer antigen 125 (CA-125), Carbohydrate antigen 19-9 (CA19-9), Krebs von den Lungen-6 (KL-6), Surfactant protein D (SP-D), C-C Motif Chemokine Ligand 18 (CCL18), matrix metalloproteinase7 (MMP7), von Willebrand factor (vWF); Biomarkers elevated in COVID-19 patients incl. ferritin, Interleukin 6 (IL-6), C-reactive protein (CRP) , monocyte chemoattractant protein-1 (MCP1), Macrophage Inflammatory Protein-1 alpha (MIP1a), Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF)
Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes. Patient Health Questionnaire 9 (PHQ-9)	72 weeks	Change from baseline Quality of Life (QoL) questionnaires from baseline to 24, 36, 48 and 72 weeks.; Patient Health Questionnaire 9 (PHQ-9); This is a 9-item questionnaire. Questions are answered from 0-3; 0- Not at all; 1. Several Days; 2. More than half the days; 3. Nearly every day
Changes from baseline and evidence of disease progression per the Quality of Life reported outcomes- Impact of Events Scale Revised (IES-R)	72 weeks	Change from baseline Quality of Life (QoL) questionnaires from baseline to 24, 36, 48 and 72 weeks.; Impact of Events Scale Revised (IES-R); 22 item patient reported outcome to measure affect of routine life stress, everyday traumas and acute stress, and potential Post Traumatic Stress Disorder (PTSD). Each question is answered from 0 to 4.; 0- Not at all; 1. A little bit; 2. Moderately; 3. Quite a bit; 4. Extremely; Scores 24 or higher- PTSD is a clinical concern Scores 33 or higher- best cutoff for probable diagnosis of PTSD Scores 37 or higher- enough to suppress immune system

Trial Locations

Locations (4)

Weill Cornell Medicine; 🇺🇸 New York, New York, United States

Washington University of St. Louis; 🇺🇸 Saint Louis, Missouri, United States

New York University Langone Medical Center; 🇺🇸 New York, New York, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States