Epidemiology, Immunology and Clinical Characteristics of COVID-19 (EPIC3) (EPIC3)

CSP #2028 - Epidemiology, Immunology and Clinical Characteristics of COVID-19 (EPIC3) Within the Veterans Health Administration

The purpose of this research is to gather information to answer questions about the Coronavirus Disease 2019 (COVID-19) which is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. This study will collect information and biological specimens from participants who have been tested for the SARS-CoV-2 infection. By doing this study, the investigators hope to learn important new information about SARS-CoV-2 infections and the potentially severe outcomes of COVID-19 to find better ways to manage and treat it in the future. The investigators also hope to learn what makes some people more susceptible to infection to help better inform Veterans on how to reduce their risk of infection. This study also involves the development and maintenance of a participant registry, a data repository, and a biorepository for future research.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2

Detailed Description

The objective of the study is to answer key research questions about the SARS-CoV-2 infection and COVID-19 natural history, clinical outcomes, and the development of immunity while also gathering biospecimens for future study as questions emerge about this new pathogen. The study is an observational cohort study of Veterans that is designed to gather longitudinal data on the epidemiology, virology, immunology, and clinical characteristics of the SARS-CoV-2 infection and COVID-19 disease during this early pandemic period while remaining flexible to the evolving needs of the Veterans Health Administration (VHA) system and emerging scientific questions. The study will enroll Veterans with and without SARS-CoV-2 infection in the inpatient, outpatient, and Community Living Center (CLC) extended care settings. Study procedures include questionnaires, clinical data abstraction from VHA electronic health records, and biological sampling. A key contribution of this study is to establish a research clinical and laboratory data repository and related research specimen repository, and participant registry for future studies of COVID-19, which is a newly emerging pandemic disease, and other health conditions. Finally, a long-term goal of this study is to provide the lessons learned from this COVID-19 pandemic to better anticipate and manage pandemics in the future for VHA and the general population.

There are 4 primary aims to this study: (1) identify patterns of SARS-CoV-2 viral shedding from multiple body sites in inpatient Veterans with COVID-19 infection during hospitalization through 28 days of follow-up; (2) characterize development of immunity among inpatient and outpatient Veterans with COVID-19 from the first VHA encounter through 24 months; (3) determine predictors of infection and disease course, severity and related death among inpatient and outpatient Veterans with and without SARS-CoV-2 infection and/or COVID-19 disease over 24 months; and (4) determine individual and health-facility-level risk factors for infection (including asymptomatic infection) with SARS-CoV-2 among Veterans at high risk for COVID-19 disease who are living in VHA Community Living Centers.

Veterans are likely to be substantially affected by COVID-19 due to a high prevalence of risk factors for severe COVID-19 disease. Understanding demographic, medical, and social factors that confer risk for severe COVID-19 disease is critical for improving care for Veterans with COVID-19. Characterizing viral shedding of SARS-CoV-2 infection during COVID-19 illness may yield important insight about factors that affect SARS-CoV-2 transmission. Characterizing the development of immunity among persons with COVID-19 is foundational to developing effective vaccines against the disease. Better understanding transmission risk and risk factors in the setting of VHA Community Living Centers will help prevent future infections.

• Study Type: Observational
• Enrollment (Actual): 2824

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304-1207
      • VA Palo Alto Health Care System, Palo Alto, CA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population is VA medical center inpatients, outpatients, and residents at Community Living Centers who meet the inclusion and exclusion criteria and are receiving healthcare at one of the VHA medical centers serving as study sites.

Description

Inclusion Criteria:

• Eligible inpatient cohort participants include Veterans with confirmed, suspected, or unsuspected COVID-19 who receive inpatient care at VHA facilities
• Eligible outpatient cohort participants include Veterans who seek care in (1) VA medical center emergency departments, (2) VA medical center urgent care clinics, or (3) VA medical center COVID-19-specific testing sites, and who are tested for SARS-CoV-2 but do not require hospital admission at the time of evaluation
• Eligible Community Living Center cohort participants include all residents who reside in VA medical center-operated Community Living Centers

Exclusion Criteria:

• Veterans without a legally authorized representative who are unable to provide consent
• Potential participants who are not Veterans
• Veterans who are illiterate or have limited or no English language proficiency

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Inpatient Cohort; COVID-19-positive or -suspected inpatients: Eligible inpatient cohort participants include Veterans who receive inpatient care at VHA facilities and are tested for SARS-CoV-2. Members of this inpatient cohort include those with and without SARS-CoV-2 infection.
Outpatient Cohort; COVID-19-positive or -suspected outpatients: Eligible outpatient cohort participants include Veterans who seek care in (1) VA medical center emergency departments, (2) VA medical center urgent care clinics, or (3) VA medical center COVID-19-specific testing sites, and who are tested for SARS-CoV-2 but do not require hospital admission at the time of evaluation. Members of this outpatient cohort include those with and without SARS-CoV-2 infection.
Community Living Center Cohort; Community Living Center residents: Eligible Community Living Center cohort participants include all residents who reside in VA medical center-operated Community Living Centers. Members of this Community Living Center cohort include those with and without SARS-CoV-2 infection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health Status Change	Mortality	Day 0 (enrollment) through 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral shedding	SARS-CoV-2 RNA from respiratory or gastrointestinal sampling sites	Day 0 (enrollment) through 6 months
Immunity	SARS-CoV-2 IgM and IgG serum antibody titers	Day 0 (enrollment) through 6 months

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Study Chair: Jennifer S Lee, MD PhD MA, VA Palo Alto Health Care System, Palo Alto, CA; Study Chair: Nicholas L. Smith, PhD, VA Puget Sound Health Care System Seattle Division, Seattle, WA

Publications and helpful links

General Publications

• Huang L, Li X, Kamal SI, Sugimoto JD, Liu CH, Wang T, Morelli DK, Midthun JB, Pakanati VR, Deardorff KV, Sporleder JL, Lopez J, Holodniy M, Smith NL, Lee JS, Shah JA, Ross JM. Epidemiology, Immunology and Clinical Characteristics of COVID-19 (EPIC3)-Database of a prospective longitudinal observational study within the Veterans Health Administration. Front Public Health. 2025 Jun 2;13:1535315. doi: 10.3389/fpubh.2025.1535315. eCollection 2025. No abstract available.
• Ross JM, Sugimoto JD, Timmons A, Adams J, Deardoff K, Korpak A, Liu C, Moore K, Wilson D, Bedimo R, Chang KM, Cho K, Crothers K, Garshick E, Gaziano JM, Holodniy M, Hunt CM, Isaacs SN, Le E, Jones BE, Shah JA, Smith NL, Lee JS; EPIC Investigators. Early Outcomes of SARS-CoV-2 Infection in a Multisite Prospective Cohort of Inpatient Veterans. Open Forum Infect Dis. 2023 Jun 27;10(7):ofad330. doi: 10.1093/ofid/ofad330. eCollection 2023 Jul.
• Li X, Pakanati V, Liu C, Wang T, Morelli D, Korpak A, Baraff A, Isaacs SN, Vittor A, Chang KM, Le E, Smith NL, Lee JS, Ross JM, Shah JA; EPIC3 Investigators. Peripheral blood cytokine profiles predict the severity of SARS-CoV-2 infection: an EPIC3 study analysis. BMC Infect Dis. 2025 May 8;25(1):677. doi: 10.1186/s12879-025-10914-6.

Helpful Links

• Seattle Epidemiologic Research and Information Center
• VA Cooperative Studies Program

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2020
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Actual): July 9, 2025
• Last Update Submitted That Met QC Criteria: July 3, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; Observational; Cohort; Critical care; Infectious disease; Prospective; Chronic diseases; Epidemiologic; Specimen banking
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: 2028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data may be shared dependent upon data safeguards and IRB approvals.
• IPD Sharing Time Frame: Data will be made available for sharing 1 year after the publication of the last manuscript addressing the primary aims of the study.
• IPD Sharing Access Criteria: The VA Cooperative Studies Program (CSP) has a program for sharing CSP study data: Integrated Veteran Epidemiologic Study Data Resource (INVESTD-R). The INVESTD-R website is where information is provided on CSP studies with data that can be shared for secondary analyses or to support new data collection from study members who consented to be recontacted. Data will be shared with qualifying investigators at bona fide research institutions.
• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No