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.
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.
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For a concise overview of current VA Health Services Research and Development (HSR&D) efforts on COVID-19, visit COVID-19 Efforts.
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)
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.
Commentary
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.
Photo: ©iStock/South_agencyTo 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.
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:
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.
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.
