COVID Cohort Study

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04393155
• Other study ID #: 16-540
• Status: Terminated
• Start date: April 16, 2020
• Est. completion date: January 25, 2021

Study information

• Verified date: February 2021
• Source: University of Vermont
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: January 25, 2021
• Est. primary completion date: January 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Respiratory Failure
• COVID-19
• Respiratory Insufficiency

Intervention

Other:
• COVID-19+ observational
This is observational -- there is no intervention

Locations

Country	Name	City	State
United States	University of Vermont College of Medicine	Burlington	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
University of Vermont

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Six minute walk distance (6MWD)	Exercise capacity	3 months after hospital admission
Secondary	Six minute walk distance (6MWD)	Exercise capacity	6 months, 12 months after hospital admission
Secondary	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
Secondary	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
Secondary	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
Secondary	Health Care Utilization Survey (HUS)	Health Care Utilization	3 months, 6 months, 12 months after hospital admission
Secondary	Death	Mortality	3 months, 6 months, 12 months after hospital admission
Secondary	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
Secondary	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
Secondary	4-meter timed walk	Gait speed	3 months, 6 months, 12 months after hospital admission
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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