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VA research during the COVID-19 pandemic

Active VA studies on COVID-19
View active VA studies on COVID-19: Map view | List view


In response to the COVID-19 pandemic, VA Research has undertaken a wide array of activities to support and advance VA's clinical and research missions and help Veterans affected by the disease. These efforts have spanned biomedical research, therapeutics and vaccine clinical trials, and data analyses that leverage VA's rich electronic health record system. VA Research has coordinated closely with internal VA and external partners—such as the National Institutes of Health and other federal agencies, and pharmaceutical companies—to identify the areas in which VA's nationwide research capacity, resources, and infrastructure could make the greatest contribution.

On this web page, we summarize recent and current COVID-19 research across the VA system.


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Active and Recently Completed Research

Clinical trials

As of mid-May 2021, more than 60 VA medical centers are involved in one or more COVID-19 clinical trials. Below are several examples. A full list of COVID-19 Clinical Trials in VA is also available.

Observational studies

  • Natural history study—VA is collaborating with the Department of Defense on an observational, natural history study of COVID-19 illness titled “Epidemiology, Immunology and Clinical Characteristics of COVID-19” (EPIC3). Researchers will collect data and biospecimens from volunteers for up to two years to better understand the clinical course of COVID-19. Recruitment at up to 16 sites began in July 2020.
  • COVID-19 and cancer—The National Cancer Institute COVID-19 in Cancer Patients Study, or NCCAPS, is a natural history study of COVID-19 in people with cancer. In a natural history study, researchers follow people and collect medical and other information about them over time to learn more about how a disease and its symptoms develop and change. Diagnosis and treatment of a disease are not part of natural history studies. The knowledge gained through this study will help doctors better manage treatment for people with cancer and COVID-19 in the future. As part of the NCCAPS study, researchers will collect blood samples, medical information, and medical images from 2,000 people with cancer who also have COVID-19. Each person will be followed for up to two years to help doctors understand how cancer affects COVID-19 and COVID-19 affects cancer. The study is recruiting volunteers nationwide, including at 11 VA locations.

Data analysis projects

  • COVID-19 Insights Partnership—VA is a key partner in the COVID-19 Insights Partnership, along with the departments of Energy (DOE) and Health and Human Services (HHS). The initiative aims to coordinate and share health data as well as research and expertise to aid in the fight against COVID-19.The Partnership creates a framework for VA and HHS to use DOE’s world-leading high-performance computing and artificial intelligence resources to conduct COVID-19 research and analyze health data.
  • Million Veteran Program—VA’s Million Veteran Program (MVP) has deployed a COVID-19 questionnaire to participants to collect information about their experience with COVID-19. In addition, MVP has prioritized a series of research questions to examine the genetic basis of infection by SARS CoV-2; complications of infection; disease severity and outcomes; and response to various medications. MVP will also seek to identify disease mechanisms and new treatment targets for COVID-19. Given MVP’s racially and ethnically diverse participant population (~ 20% African American and 7% Hispanic), the influence of race and ethnicity on disease susceptibility, severity, and outcomes will be an integral part of the analyses.
  • Synthesizing evidence from publications—Researchers from the HSR&D Evidence Synthesis Program are working to help synthesize publications about the novel coronavirus and COVID-19, and to translate that information quickly into usable guidance for clinicians. The ESP’s completed reports can be found here.
    Additional evidence reviews can be found at www.covid19reviews.org. The goal of this resource is to capture the work of evidence synthesis groups, like VA’s, around the US and the globe, and thereby avoid duplication of effort and maximize the contribution of these researchers. The catalog is maintained by the VA ESP Coordinating Center in Portland, Oregon. New evidence reviews and reviews in progress are identified through literature searching and correspondence with colleagues and content experts. The team has also set up a listserv to facilitate collaboration among systematic review researchers.
  • International collaboration—Researchers with the VA Informatics and Computing Infrastructure team are participating in the Observational Health Data Sciences and Informatics (or OHDSI, pronounced "Odyssey") program, an international, interdisciplinary collaborative to maximize the value of health data through large-scale analytics.
  • COVID Observational Research Collaboratory—A VA research initiative is bringing together VA experts to analyze the use and effects of COVID-19 drugs with clinical partners interested in the safety and efficiency of these therapies. VA’s Health Services Research and Development Service, Clinical Science Research and Development Service, and Cooperative Studies Program established the collaboratory soon after the pandemic took hold earlier this year.
  • Dementia patients—VA researchers in Providence have funding from the National Institute on Aging to study COVID-19 risk factors and outcomes among Veterans with dementia who live in VA community living centers.

Other research activities

  • COVID-19 and mental health—In addition to studying how to prevent or treat COVID-19, VA is examining the mental health impact of the pandemic. To date, ORD has funded nearly 30 studies looking at mental, behavioral, and social health and COVID-19. Some are new projects focused wholly on COVID-19, whereas others are supplements to existing projects that are broader in scope. The following study titles indicate some of the themes being explored:
    • Inflammatory and Mental Health Sequelae of COVID-19 in Veterans
    • An Integrative Technology Approach to Home-Based Conjoint Therapy for PTSD  
    • Impact of COVID-19 On Mental Health, Relationship Functioning and VA Telemental Health Service Use in a Longitudinal Cohort Study    
    • Impact of COVID-19 and Social Distancing on Mental Health and Suicide Risk in Veterans
    • Piloting a Self-Help Intervention to Improve Veteran Mental Health During the COVID-19 Pandemic
    • Mixed-Methods Pilot Study of the Impacts of Telemental Healthcare for High-Risk Veterans with Opioid Use Disorder During COVID-19
    • Adapting Caring Contacts to Counteract Adverse Effects of Social Distancing among High-Risk Veterans During the COVID-19 Pandemic
    • Virtual Pain Care for High-Risk Veterans on Opioids During COVID-19 (and Beyond)
    • Changes in the Delivery of Evidenced-Based Psychotherapies for Depression and PTSD as the Result of the COVID-19 Pandemic
    • Impacts of COVID-19 on African American Veterans with Chronic Pain
  • Biomedical studies—VA biomedical researchers are part of the fight against COVID-19. The following project titles illustrate the scope of the VA lab studies already completed or being conducted to better understand how the virus works, and to identify new ways to keep it from spreading and causing disease.
    • 3D-Printed Respirator Mask Performance with and without Virus Inactivation 
    • A Safe Validation to Test the Efficacy of Disinfectants on Reusable 3D-Printed Face Masks During the COVID-19 Pandemic 
    • Leukocyte Rewiring as a Mechanism of COVID-19-ARDS 
    • Viral and Immune Dynamics of Sars-Cov-2 Infection in Moderate and Severe COVID-
    • Predictive Immune and Airway Monitoring in Healthcare Workers and Hospitalized COVID-19 Patients 
  • Boosting the VA supply chain—Rehabilitation researchers are helping to build a more resilient supply chain for VA. Researchers from several centers are involved, such as the Human Engineering Research Laboratories (HERL) in Pittsburgh; the Center for Limb Loss and Mobility at the Puget Sound VA; the Minneapolis Adaptive Design and Engineering Program; and the Advanced Platform Technology Center in Cleveland. Partners in this effort include the VA Innovation Ecosystem, the U.S. Food and Drug Administration, the National Institutes of Health, and America Makes. These researchers and their colleagues have been designing, fabricating, and evaluating personal protective equipment (PPE) and other supplies to support VA’s response to this pandemic, such as masks, face shields, desk shields, nasal testing swabs. In many cases, 3D printing is involved.

COVID-19 work highlighted on HSR&D site

For a concise overview of current VA Health Services Research and Development (HSR&D) efforts on COVID-19, visit COVID-19 Efforts.

Selected Studies of Note

Diabetes linked to worse COVID-19 outcomes
Diabetes is linked to worse outcomes from COVID-19 infection, according to a VA Puget Sound study. Researchers looked at outcomes form nearly 36,000 VA patients who tested positive for COVID-19. Patients with diabetes had greater odds of hospitalization, intensive care unit admission, and death than patients without diabetes. Prior use of the diabetes medication sulfonylurea was linked to increased odds of hospitalization. Prior insulin use was linked to increased odds of both hospitalization and death. Statin use was associated with lower chance of death, and angiotensin receptor blockers (ARBs) were associated with lower odds of hospitalization. The results show that diabetes increases the danger posed by COVID-19. (BMJ Open Diabetes Research and Care, June 2021)

COVID-19 vaccines largely effective in inflammatory bowel disease patients taking immunosuppressants
Vaccination against COVID-19 proved mostly effective in patients with inflammatory bowel disease, found a Michael J Crescenz VA Medical Center study. Clinical trials of COVID-19 vaccines mostly excluded patients taking immunosuppressive medication. The researchers studied outcomes for nearly 15,000 patients taking medication for inflammatory bowel disease. Full vaccination—meaning patients were at least a week past the second vaccine dose—showed 80% effectiveness against COVID-19. Unvaccinated patients in this population had a much higher rate of COVID-19 infection than vaccinated patients. Partial vaccination did not significantly reduce the hazard of infection. The results could help increase patient and provider willingness to vaccinate immunosuppressed patients, say the researchers. (Gastroenterology, May 25, 2021)

Potential replacement materials for N95 mask filters
Several commercially available materials could be potential replacements for filters used in N95 masks, found a study by VA Puget Sound researchers and colleagues, but downsides exist. Researchers tested 14 filter materials in a 3-D printed face mask. Several materials proved effective at blocking virus transmission. Disinfection by dry heat did not reduce the materials’ ability to block virus transmission. Ten cycles of vaporized hydrogen peroxide for disinfection significantly reduced filter efficiency. While multiple filter materials appeared to be effective potential replacements for N95 filters, they did show reduced efficiency and increased breathing resistance, compared with traditional N95 filters. (Journal of Occupational and Environmental Hygiene, May 14, 2021)

Lower job-person fit leads to more health care worker burnout during the pandemic
Health care workers with lower job-person fit were more likely to feel burnout during the COVID-19 pandemic, found a VA study. Job-person fit was defined as how well worker expectations met workplace realities. Researchers surveyed 147 health care workers in the summer of 2020. Of those, 43% reported burnout. Those who felt better about being recognized or appreciated for their work and who felt that their goals and values aligned with organization goals and values were less likely to feel burnout. Addressing job-person fit may be key to reducing burnout during health crises, according to the researchers. (Journal of Occupational and Environmental Medicine, May 14, 2021)

COVID-19 ‘long-haulers’ face increased risk of death and many other health problems
A large VA study showed that people who have had COVID-19 are at heightened risk of both death and many other health problems. In the largest post-acute COVID-19 study to date, VA Saint Louis Health Care System researchers characterized many potential long-term consequences of COVID-19. The researchers looked at outcomes on more than 73,000 VA patients who survived COVID-19 and close to 5 million who did not contract the disease. The COVID-19 group had a higher risk of dying six months after diagnosis. People who have recovered from COVID-19 also are at increased risk of health problems affecting virtually every organ system in the body, not just the lungs. About 8% to 10% of people affected by COVID-19 will likely have long-term effects, according to the researchers. (Nature, April 22, 2021)

View all studies

Selected Scientific Articles by VA Researchers

Clinical Trials

Baricitinib plus remdesivir for hospitalized adults with Covid-19. Kalil AC, et al. Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with COVID-19, notably among those receiving high-flow oxygen or noninvasive ventilation. N Eng J Med. 2021 Mar 4;384(9):795-807.

A neutralizing monoclonal antibody for hospitalized patients with Covid-19. ACTIV-3/TICO LY-CoV555 Study group, Lundgren JD, et al. Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had COVID-19. N Engl J Med. 2020 Dec 22. Online ahead of print.

Laboratory Studies

Structure-based phylogeny identifies avoralstat as a TMPRSS2 inhibitor that prevents SARS-CoV-2 infection in mice. Sun YJ, Velez G, Parsons DE, Li K, Ortiz ME, Sharma S, McCray PB Jr, Bassuk AG, Mahajan VB. Using a mouse model, researchers identified a chemical compound that could be repurposed to help prevent COVID-19 infection. Journal of Clinical Investigation. 2021 May 17;131(10):e147973.

Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARS-CoV-2 Nsp12. Teng Y et al. Researchers identified a structure created by lung cells when exposed to the COVID-19 virus that potentially plays and role in lung inflammation. Mol Ther. 2021 May 10. Online ahead of print.

Hypoxia induces expression of angiotensin-converting enzyme II in alveolar epithelial cells: Implications for the pathogenesis of acute lung injury in COVID-19. Sturrock A, Zimmerman E, Helms M, Liou TG, Pain R 3rd. Increases of the ACE2 protein in lung cells caused by hypoxia (lack of oxygen) may explain how acute respiratory distress syndrome develops in COVID-19, according to a mouse model. Physiological Reports. 2021 May;9(9):e14854.

Mucosal associated invariant T (MAIT) cell responses differ by sex in COVID-19. Yu C, Littleton S, Giroux NS, Mathew R, Ding S, Kalnitsky J, Yang Y, Petzold E, Chung HA, Rivera GO, Rotstein T, Xi R, Ko ER, Tsalik EL, Sempowski GD, Denny TN, Burke TW, McClain MT, Woods CW, Shen X, Saban DR. The findings uncover a female-specific protective immune cell profile, potentially shedding light on reduced COVID-19 susceptibility in females. Med (N Y). 2021 Apr 13. Online ahead of print.

Blockade of SARS-CoV-2 spike protein-mediated cell-cell fusion using COVID-19 convalescent plasma. Wang L, Zhao J, Nguyen LNT, Adkins JL, Schank M, Khanal S, Nguyen LN, Dang X, Cao D, Thakuri BK, Lu Z, Zhang J, Zhang Y, Wu XY, El Gazzar M, Ning S, Moorman JP, Yao ZQ. COVID-19 convalescent plasma may not only inhibit SARS-CoV-2 spike proteins, but also neutralize the virus’s ability to cross cell membranes. Sci Rep. 2021 Mar 10;11(1):5558.

Data Analysis/Review

Increased procoagulant platelet levels are predictive of death in COVID-19. Khattab MH, Prodan CI, Vincent AS, Xu C, Jones KR, Thind S, Rabadi M, Mithilesh S, Mathews E, Guthery L, Dale GL, Kirkpatrick. Platelet procoagulant potential is decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Geroscience. 2021 June 9. Online ahead of print.

Association of social and behavioral risk factors with mortality among US Veterans with COVID-19. Kelly JD, Bravata DM, Bent S, Wray CM, Leonard SJ, Boscardin WJ, Myers LJ, Keyhani S. In an integrated health system such as VA, social and behavioral risk factors were not associated with mortality from COVID-19. JAMA Netw Open. 2021 Jun 1;4(6):e2113031.

Designing COVID-19 mortality predictions to advance clinical outcomes: Evidence from the Department of Veterans Affairs. Makridis CA, Strebel T, Marconi V, Alterovitz G. The study shows how artificial intelligence recommendations can be mad explainable and practical for clinicians and their interactions with patients. BMJ Health Care Inform. 2021 Jun;28(1):e100312.

Mental health and suicidal ideation in US military veterans with histories of COVID-19 infection. Na P, Tsai J, Harpaz-Rotem I, Pietrzak R. Psychiatric symptoms and suicidal ideation are prevalent in Veterans who have survived COVID-19. Veterans with greater prepandemic psychiatric and substance use problems, COVID-19-related stressors, and fewer psychosocial resources may be at increased risk of these outcomes. BMJ Military Health. 2021 May 25. Online ahead of print.

A qualitative study of the impact of COVID-19 on smoking behavior for participants in a post-hospitalization smoking cessation trial. Schnitzer K, Jones S, Kelley JHK, Tindle HA, Rigotti NA, Kruse GR. Stress during the COVID-19 pandemic may undermine effective coping skills among individuals enrolled in a smoking cessation trial. Int J Environ Res Public Health. 2021 May 19;18(10):5404.

Other Research

Suicidal ideation and thoughts of self-harm during the COIVD-19 pandemic: The role of COVID-19-related stress, social isolation, and financial strain. Elbogen EB, Lanier M, Blakey SM, Wagner HR, Tsai J. COVID-19-related stress symptoms, loneliness, and financial strain were associated with thoughts of suicide and self-harm. Depress Anxiety. 2021 May 5. Online ahead of print.

Increasing facemask compliance among healthcare personnel during the COVID-19 pandemic. Datta R, Glenn K, Pellegrino A, Tuan J, Linde B, Kayani J, Patel K, Carlo L, Dembry LM, Fisher A. Facemask compliance remains suboptimal among health care personnel despite a facility-wide mandate for universal masking. Infect Control Hosp Epidemiol. 2021 May 3:1-22.

Psychological distress and alcohol use disorder during the COVID-19 era among middle- and low-income U.S. adults. Tsai J, Elbogen EB, Huang M, North CS, Pietrzak RH. Predisposing factors are stronger predictors of psychological distress than personal COVID-19 infection or exposure during the pandemic. J Affect Disord. 2021 April 4;288:41-49.

Association of symptoms of posttraumatic stress disorder with posttraumatic psychological growth among US Veterans during the COVID-19 pandemic. Pietrzak RH, Tsai J, Southwick SM. Many Veterans reported positive post-traumatic growth related to dealing with the pandemic, with this effect highest in those who screened positive for COVID-19-associated PTSD symptoms. JAMA Netw Open. 2021 Apr 1;4(4):e214972.

Association between risk factors for complications from COVID-19, perceived chances of infection and complications, and protective behavior in the US. Schoeni RF, Wiemers EE, Seltzer JA, Langa KM. Adults with risk factors for COVID-19 complications reported higher perceived susceptibility to complications. During common activities, the majority of adults, including the highly susceptible, did not consistently wear masks. JAMA Netw Open. 2021 Mar 1;4(3):e213984.


The face mask at the intersection of prevention science, domestic politics, and international diplomacy: A historical perspective. Kristo G, He K, Whang E, Fisichella PM. From a historical perspective, when cooperation rather than division becomes the norm in the global response to pandemics, the face mask can then unite rather than divide us. J Laparoendosc Adv Surg Tech A. 2021 Apr 23. Online ahead of print.

COVID-19 Insights Partnership: Leveraging big data from the Department of Veterans Affairs and supercomputers at the Department of Energy under the Public Health Authority. Ramoni R, Klote M, Muralidhar S, Brandt C, Bernstein MA, McMahon BH, Jacobson DA, Justice AC. Investigators from multiple federal agencies will be able to combine DOE’s high-performance computing and artificial intelligence expertise with health information from Veterans and non-Veterans diagnosed with COVID-19 to bolster the nation’s ability to understand, prevent, and treat the disease. J Am Med Inform Assoc. 2021 Mar 29. Online ahead of print.

The Veterans Health Administration approach to COVID-19 vaccine allocation—Balancing utility and equity. Tarzian AJ, Geppert CMA. VHA was able to mobilize early to identify vaccine allocation guidelines and proactively prepare facilities to vaccinate VHA staff and Veterans as soon as vaccines were approved. Fed Pract. 2021 Feb;38(2):52-54.

An issue of trust—Vaccinating Black patients against COVID-19. Okorodudu DO, Okorodudu DE. Trust needs to be built through transparency and partnership to further COVID-19 vaccination in the Black community and other vulnerable populations. Lancel Respir Med. 2021 Jan 19. Online ahead of print.

Does universal testing for COVID-19 work for everyone? Dumyati G, Gaur S, Nace DA, Jump RLP. The authors propose a structured approach for facility-wide testing of nursing home residents and staff. J AM Med Dir Assoc. 2020 Nov;21(11):1525-1532.

Infectious disease specialist consultation improves long-term <em>S. aureus</em> outcomes - Photo: ©iStock/South_agencyPhoto: ©iStock/South_agency

To rapidly stand up new research and optimize resources during the COVID-19 pandemic, the VA Office of Research and Development (ORD) has coordinated with the National Institutes of Health, the Department of Defense, the Department of Energy, other federal agencies, and several industry partners—namely, pharmaceutical companies. Further, as part of the larger Veterans Health Administration system, ORD has supported other VHA offices by providing research expertise and personnel to assist with public health and informational demands.

Prior to the pandemic, ORD had been pursuing three strategic priorities: enhancing Veteran access to clinical trials; putting VA data to work for Veterans; and increasing the real-world impact of VA research. These priorities continue to guide ORD’s efforts and have positioned the program to quickly respond to COVID-19 through the creation and expansion of research partnerships; optimization of resource allocation; and streamlining and modernization of  processes and policies. Part of this effort has involved creating new ways to rapidly support VA investigators eligible for VA research funding, and quickly evaluating research ideas proposed by VA scientists.

Contributing to understanding COVID-19 and potential treatments

ORD is engaged in a wide array of research activities on COVID-19, with the support and cooperation of many internal VA and external partners. These activities encompass a range of studies, as well as innovative approaches to planning, coordinating, and expediting research:

  • Working with industry partners to include VA sites in clinical trials for new treatments. In one case, through a coordinated effort, VA was able to get a trial started in under a week—a dramatic reduction over the usual timeframe.

  • Coordinating with other federal agencies on national-scale studies on understanding the natural history of and treatments for COVID-19 or specimen collections from patients with COVID-19, to aid in vaccine and therapeutics development.

  • Facilitating expanded access (a.k.a. compassionate use) of investigational medications pending FDA approval. Efforts have included establishing a regulatory and pharmaceutical support team consisting of more than 80 VA research field staff for helping facilities obtain approvals for use of these medications.

  • Creating opportunities to rapidly fund VA investigators with meritorious research proposals on COVID-19.

  • Quickly evaluating research ideas proposed by VA scientists, in large part through a steering committee composed of leading VA experts in virology, infectious disease, and epidemiology.

  • Using data and informatics expertise to create common elements for harmonizing research and examining off-label use of approved medications.

  • Rapidly synthesizing evidence from the available scientific literature, and translating this evidence into usable guidance for clinicians in VA and beyond.

  • Coordinating the establishment of a central VA COVID-19 registry and biorepository.

Ensuring the safety and well-being of research personnel and study participants

To help prevent the spread of COVID-19, reduce exposures among both research staff and patients, and decrease the burden on the health care system, ORD instituted an administrative hold that stopped non-critical, in-person research contacts for all VA-funded research. (Some of this activity has begun to resume as of June, depending on local conditions.) Additional guidance was issued to ensure the safety and protection of all those involved in research. To ensure communication and understanding, ORD has developed a common communication platform for providing written guidance and sharing resources and tools, issued FAQs for field staff, and conducted a series of informational webinars for VA research personnel.

Enabling continuity of operations

As protective measures were implemented for personnel, ORD recognized the importance of continuing research when possible, given the public investments made to date. In this context, regulatory guidance was issued on options and requirements for conducting research through alternative methods. Additionally, ORD worked with the VA Office of Information Technology to issue guidance on the use of communication technologies for research purposes. A field operations workgroup was also set up to examine ongoing research challenges and to develop more uniform guidance for all research programs.

Questions about the R&D website? Email the Web Team.

Any health information on this website is strictly for informational purposes and is not intended as medical advice. It should not be used to diagnose or treat any condition.