VA research during the COVID-19 pandemic
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.
Active and Recently Completed Research
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.
- VA CURES—The wide-reaching “VA CURES” master protocol, launched in August 2020, enables a series of clinical trials across VA, the first one involving 702 Veterans who are hospitalized for COVID-19 from 25 VA sites. The study is examining the effects of convalescent plasma. VA CURES stands for “Coronavirus Research and Efficacy Studies.” The initiative aims to give Veterans faster access to potential COVID-19 treatments and to test their effectiveness. As a master protocol, VA CURES offers a standardized framework for studies on many potential treatments for COVID-19, without the need for a new study design and protocol each time.
- VA has been part of two major national research initiatives on COVID-19 vaccines and therapeutics: Operation Warp Speed (OWS) and the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative.
- Through OWS and other efforts, VA has been an active participant in several clinical trials designed to evaluate potential COVID-19 vaccines. These trials have included:
- The Moderna/COVE trial, which took place at one VA site and is now closed to enrollment. In December 2020, Moderna obtained an emergency use authorization for its vaccine from the FDA.
- The AstraZeneca trial, now closed to enrollment.
- The Janssen ENSEMBLE trial, which included 17 VA sites and is now closed to enrollment. The vaccine received FDA emergency use authorization in late February 2021.
- The Pfizer trial, now closed to enrollment. In December 2020, Pfizer obtained an emergency use authorization for its vaccine from the FDA.
- The Novavax trial, now closed to enrollment in VA.
- ACTIV-3, an inpatient trial of a monoclonal antibody, is expected to involve about 20 VA medical centers. This trial involves inpatients and has been testing combinations of monoclonal antibodies and antiviral drugs.
- Trials with industry—VA took part in a number of industry-sponsored studies of promising medications for COVID-19. These included, for example, studies of the drug tocilizumab with Hoffman-La Roche, and sarilumab with Regeneron. Both drugs are used in arthritis care and block an inflammatory protein known as IL-6.
- Remdesivir trial with NIH—VA sites took part in a randomized, placebo-controlled study of remdesivir and other medications for hospitalized patients with COVID-19, sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
- 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
Nasal swab COVID-19 test less sensitive, easier than sinus swab
Nasal swabs are less sensitive than deeper sinus swabs at detecting the virus that causes COVID-19 but are still highly accurate, found a study by a VA researcher. The “gold standard” for detecting SARS-CoV-2 is a nasopharyngeal swab, which takes a sample from the back of the sinuses through the nose. Researchers reviewed studies of how effective this type of COVID-19 test was compared with nasal swabs taken from the nostrils. They found that nasal swabs were 82% to 88% effective at detecting the virus, compared with 98% for nasopharyngeal swabs. However, nasal swabs are quicker to perform and require less protective equipment. The lower sensitivity of nasal swabs is balanced by the ability to screen more patients and the easier procedure, conclude the researchers. (PLoS One, July 20, 2021)
Remdesivir linked to longer hospital stays for COVID-19 patients
Remdesivir treatment was associated with longer hospital stays for COVID-19 patients, in a study by Iowa City VA researchers. Previous studies suggested that the drug remdesivir can reduce recovery time for COVID-19 patients. Researchers looked at data on nearly 6,000 Veterans treated for COVID-19 at VA medical centers. Of those, 40% received remdesivir. Patients given remdesivir had longer median hospital stays than patients not treated with the drug. Remdesivir did not appear to reduce patients’ 30-day risk of death. Because the treatment lasts several days, remdesivir may increase the need for hospital beds for COVID-19 patients while not improving survival, say the researchers. (JAMA Network Open, July 1, 2021
No benefit for COVID-19 patients from hydroxychloroquine
Hydroxychloroquine does not appear to offer any benefit to hospitalized COVID-19 patients, found a large VA study. Researchers looked at data on more than 64,000 VA patients tested for COVID-19. More than 7,000 positive cases were found, of which nearly 3,000 required hospitalization. Of those, 657 Veterans were prescribed hydroxychloroquine. The data show no apparent benefit for the patients given hydroxychloroquine, either alone or combined with azithromycin. Those given both hydroxychloroquine and azithromycin had an increased risk of intubation. The results show that hydroxychloroquine does not improve survival for COVID-19 patients, concluded the researchers. (American Journal of Epidemiology, June 24, 2021)
Social and behavioral risk factors did not increase COVID-19 mortality risk in Veterans
Social and behavioral risk factors were not associated with death from COVID-19 in VA patients, in a study of more than 27,000 Veterans. Researchers looked at data on Veterans with a positive COVID-19 test between March and September of 2020. They found that Veterans with risk factors traditionally associated with barriers to care had no higher risk of dying from COVID-19 than patients without those risk factors. Social risk factors including housing problems and financial hardship. Behavioral risk factors included tobacco, alcohol, and drug use. The results show that an integrated health system such as VA can transcend social vulnerabilities that often lead to health care disparities, according to the researchers. (JAMA Network Open, June 9, 2021)
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)
View all studies
Selected Scientific Articles by VA Researchers
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.
SARS-CoV-2 disrupts proximal elements in the JAK-STAT pathway. Chen DY, Khan N, Close BJ, Goel RK, Blum B, Tavares AH, Kenney D, et al. This laboratory study identifies a possible biological pathway for how the SARS-CoV-2 virus infects multiple different organ cell types. J Virol. 2021 Jul 14. Online ahead of print.
SARS-CoV-2 ORF8 forms intracellular aggregates and inhibit IFNγ-induced antiviral gene expression in human lung epithelial cells. Geng H, Subramanian S, Wu L, Bu HF, Wang X, Du C, De Plaen IG, Tan XD. The protein ORF8SARS-CoV-2 appears to be involved in the process by which the lungs are damaged in COVID-19. Front Immunol. 2021 Jun 9;12:679482.
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.
Moral distress in frontline healthcare workers in the initial epicenter of the COVID-19 pandemic in the United States: Relationship to PTSD symptoms, burnout, and psychosocial functioning. Norman SB, Feingold JH, Kaye-Kauderer H, Kaplan CA, Hurtado A, Kachadourian L, Feder A, et al. Moral distress is prevalent in frontline health care workers and includes family-, infection-, and work-related concerns. Depress Anxiety. 2021 Jul 22. Online ahead of print.
Promise and perils of telehealth in the current era. Mahtta D, Daher M, Lee MT, Sayani S, Shishehbor M, Virani SS. Telehealth services have been associated with improved health care outcomes wile remaining a cost-effective mode of health care delivery. Focus is needed on access disparities. Curr Cardiol Rep. 2021 Jul 16;23(9):115.
Characteristics and outcomes of 627 044 COVID-19 patients living with and without obesity in the United States, Spain, and the United Kingdom. Recalde M, Roel E, Pistillo A, Sena AG, Prats-Uribe A, Ahmed WU, Alghoul H, et al. Obese patients present with more severe forms of COVID-19, with higher hospitalization rates and intensive service requirements. Int J Obes (Lond). 2021 Jul 15;1-11. Online ahead of print.
Short-term effects of canceled elective procedures due to COVID-19: Evidence from the Veterans Affairs healthcare system. Tran LD, Rose L, Urech T, Dalton A, Wu S, Vashi AA. The pause in elective surgical cases caused by the pandemic was not associated with shot-term adverse outcomes in VA hospitals, suggesting appropriate surgical case triage and management. Annals of Surgery. 2021 July 1;274(1):45-49.
Emerging advances of nanotechnology in drug and vaccine delivery against viral associated respiratory infection diseases (VARID). Seyfoori A, Shokrollahi Barough M, Mokarram P, Ahmadi M, Mehrbod P, Sheidary A, Madrakian T, et al. Nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral respiratory infections. Int J Mol Sci. 2021 Jun 28;22(13):6937.
Clinical and functional effects of the COVID-19 pandemic and social distancing on vulnerable Veterans with psychosis or recent homelessness. Wynn JK, McCleerey A, Novacek D, Reavis EA, Tsai J, Green MF. Although initially reporting worse clinical outcomes, Veterans with psychotic disorders and those experiencing homelessness exhibited improvements in depression and anxiety as the pandemic went on. This effect could be due to the availability of VA services. J Psychiatr Res. 2021 Jun;138:42-49.
Readability, content, and quality of COVID-19 patient education materials from academic medical centers in the United States. Kruse J, Toledo P, Belton TB, Testani EJ, Evans CT, Grobman WA, Miller ES, Lang EMS. Despite availability of web-based patient educational materials for COVID-19, the reading level was significantly higher than recommended, and usable material was low. Am J Infect Control. 2021 Jun;49(6):690-693.
An app-based intervention to support first responders and essential workers during the COVID-19 pandemic: Needs assessment and mixed methods implementation study. Vilendrer S, Amano A, Brown Johnson CG, Favet M, Safaeinili N, Villasenor J, Shaw JG, Hertelendy AJ, Asch SM, Mahoney M. First responders and essential workers both reported challenges related to obtaining accurate information, testing services, and other resources. A mobile app has the potential to combat these challenges. J Med Internet Res. 2021 May 20, 23(5):e26573.
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.
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.
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.