COVID Cohort Study

Understanding Immunology and Patient Outcomes of COVID-19: A 1-Year Longitudinal Follow-up Study of Hospitalized Patients

The novel SARS-CoV-2 virus has quickly spread worldwide, with substantial morbidity and mortality. There is very limited understanding of the short- and longer-term inflammatory/immunological and clinical course. However, the investigators expect survivors from severe COVID-19 to experience persistent functional impairments, as demonstrated in prior studies of patients with acute respiratory distress syndrome (ARDS) and other acute viral illnesses. Notably, however, few studies have ever investigated the biologic mechanisms underlying these functional impairments. Understanding these features of COVID-19 will improve the ability to design acute therapies and recovery-focused interventions. To address these knowledge gaps, the investigators propose a two-center, 225 patient longitudinal prospective cohort study of hospitalized COVID-19 patients with acute respiratory failure. Researchers will perform an in-depth evaluation of inflammatory/immunological biomarkers, and physical, pulmonary, and neuropsychological clinical outcomes during hospitalization, and over 3-, 6-, and 12-month follow-up.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Acute Respiratory Failure
• Intervention / Treatment: Other: COVID-19+ observational

Detailed Description

The novel coronavirus (SARS-CoV-2) and associated COVID-19 illness has quickly spread worldwide, with substantial morbidity and mortality. Early data suggest that most patients with severe COVID-19 (i.e., experiencing acute respiratory failure (ARF) in an intensive care unit) may have cytokine release syndrome and other major effects on the innate and adaptive immune systems. However, there is limited understanding of both the inflammatory/immunological and the clinical course of COVID-19, with no robust data published beyond hospital discharge. Based on prior literature from acute viral illnesses, such as Ebola and Severe Acute Respiratory Syndrome (SARS), persistent functional impairments in COVID-19 survivors is expected. Despite the importance of these issues, very few studies have ever investigated the biological mechanisms underlying persistent functional impairments after ARF. Hence, understanding the short- and longer-term biological and clinical outcomes of patients with COVID-19, and investigating associations between inflammation and clinical outcomes is important to design acute therapies and recovery-focused interventions.

To address critical gaps in knowledge, the investigators propose a 2-center longitudinal cohort study of hospitalized COVID-19 patients via an Administrative Supplement to our existing grant (R01HL132887, MPIs Stapleton and Needham). Investigators will study COVID-19 patients with ARF who have either severe disease (requiring mechanical ventilation, non-invasive ventilation, or high flow nasal cannula oxygen support) or non-severe disease (new or increased supplemental oxygen requirement, without meeting severe criteria). Researchers will perform an in-depth evaluation of inflammatory/immunological, physical, pulmonary, and neuropsychological status during hospitalization, and over 3, 6, and 12-month follow-up. Feasibility for accomplishing this prospective study is demonstrated by 1) a successful existing collaboration between the University of Vermont (UVM) and Johns Hopkins University (JHU), supported by multiple NIH grants, and 2) the current and projected COVID-19 census at both hospital systems. The investigators have the existing infrastructure, expertise, and personnel to enroll 225 patients with COVID-19, and longitudinally follow survivors for 12 months, to investigate short-term and longer-term inflammatory/immunologic and clinical outcomes during this pandemic.

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• United States
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This study will enroll patients hospitalized at participating medical centers who have a positive test result for COVID-19. These patients are expected to have a greater acuity of illness and burden of disease based on the fact that they require inpatient care. Enrolling hospitalized patients ensures a greater opportunity to collect serial biological specimens over the course of the illness due to proximity of the patient to medical and research staff and UVM laboratories.

Description

Inclusion Criteria:

1. Adult (≥18 years old) at the time of consent
2. Positive COVID-19 test result or highly suspicious for COVID-19 infection and have a test pending
3. Acute Respiratory Failure (new requirement for supplemental oxygen or acute increase in required supplemental oxygen)

Exclusion Criteria:

1. Expected death or withdrawal of life-sustaining treatments within 3 days
2. Unable to walk ≥150 feet prior to COVID-19 (due to 6-minute walk test being primary outcome for in-person testing)
3. Hemoglobin ≤7.0 at the time of consent
4. Pre-existing cognitive/language impairment prohibiting clinical outcomes assessment
5. Prior lung resection (due to spirometry as part of in-person outcome assessment)
6. Unable to provide consent and no legally authorized representative (LAR) identified or reached by phone
7. Pregnant
8. Incarcerated
9. Homelessness
10. Physician declines patient enrollment (attending physician or study physician)
11. Patient or LAR do not consent to participate in the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19+; Hospitalized patients with acute respiratory failure (new oxygen requirement) due to COVID-19	Other: COVID-19+ observational; This is observational -- there is no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six minute walk distance (6MWD)	Exercise capacity	3 months after hospital admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six minute walk distance (6MWD)	Exercise capacity	6 months, 12 months after hospital admission
Hospital Anxiety and Depression Scale (HADS)	Symptoms of anxiety and depression. Both anxiety and depression subscales are scored from 0-21, with higher scores indicating more symptoms.	3 months, 6 months, 12 months after hospital admission
EuroQol Group standardized measure of health status (EQ-5D-5L)	Health-related quality of life. The EQ-5D-5L is scored from 0-100, with a higher score indicating better health status.	3 months, 6 months, 12 months after hospital admission
MoCA-BLIND	Mental and Cognitive Functioning. The MoCA-BLIND is scored from 1-22, with higher scores indicating better cognitive function.	3 months, 6 months, 12 months after hospital admission
Health Care Utilization Survey (HUS)	Health Care Utilization	3 months, 6 months, 12 months after hospital admission
Death	Mortality	3 months, 6 months, 12 months after hospital admission
Forced vital capacity (FVC)	The maximum volume of gas expired when the patient exhales as forcefully and rapidly as possible after a maximal inspiration. Obtained by spirometry.	3 months, 6 months, 12 months after hospital admission
Forced expiratory volume in 1 second (FEV1)	Measure of the volume expired over the first second of an FVC maneuver. Obtained by spirometry	3 months, 6 months, 12 months after hospital admission
4-meter timed walk	Gait speed	3 months, 6 months, 12 months after hospital admission
Peripheral blood mononuclear cell type: CD4+ T cells (#cells/ml)	Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Peripheral blood mononuclear cell type: CD8+ T cells (#cells/ml)	Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Peripheral blood mononuclear cell type: B cells (#cells/ml)	Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Peripheral blood mononuclear cell type: NK cells (#cells/ml)	Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Peripheral blood mononuclear cell type: monocytes (#cells/ml)	Measured by cell staining and flow cytometry. PBMC differentiation/ activation/exhaustion status will be determined by multicolor flow cytometry staining with human monoclonal antibodies.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Circulating markers of inflammation: C-Reactive Protein (CRP) (mg/l)	Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Circulating markers of inflammation: Interleukin 6 (IL-6) (pg/ml)	Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Circulating markers of inflammation: Interleukin 8 (IL-8) (pg/ml)	Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Circulating markers of inflammation: Interferon gamma (IFNg) (pg/ml)	Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Circulating markers of inflammation: Interferon alpha (IFNa) (pg/ml)	Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Circulating markers of inflammation: Tumor necrosis factor alpha (TNFa) (pg/ml)	Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission
Circulating markers of inflammation: Interleukin 1 beta (IL-1b) (pg/ml)	Biomarkers measured from plasma will be assayed using Luminex-based multiplex immunoassay.	study days 1, 3, and 7; then 3 months, 6 months, 12 months after hospital admission

Collaborators and Investigators

• Sponsor: University of Vermont

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2020
• Primary Completion (Actual): January 20, 2021
• Study Completion (Actual): January 25, 2021

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): February 12, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Respiratory Insufficiency
• Other Study ID Numbers: 16-540

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No