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.
Vaccines protect against hospitalization from COVID-19 Delta variant
COVID-19 mRNA vaccines are highly effective at preventing infection against the Delta variant, according to a report by VA researchers and colleagues. Researchers looked at infection rates at five VA medical centers between February and August 2021. They found that mRNA vaccines were 87% effective, including during periods of widespread circulation of the COVID-19 Delta variant. Vaccines were 80% effective at preventing COVID-19-related hospitalization in people aged 65 or older. They were 95% effective at prevention hospitalization for patients 18 to 64. The results suggest that all eligible persons should receive COVID-19 vaccination to prevent hospitalization, according to the researchers. (CDC Morbidity and Mortality Weekly Report, Sept. 10, 2021)
Immunologic resilience grades could help predict COVID-19 severity
A team with the South Texas Veterans Health Care System and the University of Texas Health Science Center at San Antonio published findings on an idea they call “immunologic resilience” that can help predict which COVID-19 patients will advance to severe disease. The research team developed “immune health grades” for more than 500 VA patients with COVID-19, based on measures of infection-fighting T cells and the expression of certain genes. The team found the metric to be “highly prognostic.” Using biomarkers to track immunologic resilience could help predict resistance not only to COViD-19, but also to other diseases such as influenza or HIV, according to the researchers. The work is part of a broader partnership between VA and the National Institute of Allergy and Infectious Diseases (NIAID), the NIH agency led by Dr. Anthony Fauci. (Journal of Allergy and Clinical Immunology, Sept. 7, 2021)
COVID-19 pandemic has not increased suicide risk in Veterans
The COVID-19 pandemic has not increased suicidal behavior among Veterans, according to a VA National Center for PTSD study. Many scholars warned that hardships and isolation caused by the pandemic could create a “perfect storm” of suicide risk among vulnerable populations. Researchers surveyed more than 3,000 Veterans in November 2019, and again in November 2020. They found that rates of suicidal thoughts actually decreased by almost 3% during the pandemic. The number of suicide attempts did not increase during the study period. However, Veterans who contracted COVID-19 were more than twice as likely to report suicidal thoughts than they were before infection. The results suggest that the resiliency of Veterans and increased social support may be protective against suicide risk during a health crisis, according to the researchers. More research is needed into how the physical and social effects of COVID-19 infection may affect suicide, they say. (JAMA Psychiatry, Aug. 25, 2021)
Severe obesity a risk factor for death from COVID-19
Severe obesity increases the risk of death from COVID-19, according to a study of VA patients. Researchers looked at outcomes for more than 16,000 VA patients hospitalized with COVID-19 between March and November of 2020. Of those, 12% died in the hospital. Severe obesity, defined as a body mass index above 40, increased the risk of death by 43%. Obesity (BMI between 30 and 40) and sleep apnea did not increase the risk of death from COVID-19. Severe obesity should be considered an underlying medical condition when prioritizing treatment and predicting severe COVID-19 risk, conclude the researchers. (International Conference on Pharmacoepidemiology & Therapeutic Risk Management, Aug. 23, 2021)
Smoking, alcohol use tied to lower mortality risk in COVID-19 patients
Risk factors for death differ in COVID-19 infected and uninfected patients, found a Durham VA and Duke University study. Researchers compared mortality rates between Veterans with and without COVID-19 who had similar risk factors. They looked at outcomes of more than 340,000 male Veterans tested for COVID-19 between March and September 2020. Of those, 7% tested positive. Older age and obesity both increased the chance of death in patients with COVID-19 beyond the risk in similar patients not infected. Surprisingly, COVID-19 patients who smoked or had alcohol use disorder had lower mortality risk than patients who did not smoke or had alcohol use disorder. Both smoking and alcohol use disorder increased mortality risk in patients without COVID-19. More study is needed on why normally harmful behaviors might be associated with better mortality outcomes in COVID-19 patients, say the researchers. (International Journal of Environmental Research and Public Health, Aug. 11, 2021)
Clinical Trials
Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): A randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Marconi VC, Ramanan AV, de Bono S, Kartman CE, Krishnan V, Liao R, Piruzeli ML et al. Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard care alone, and was associated with reduced mortality in hospitalized adults with COVID-19. Lancet Respir Med. 2021 Aug 31. Online ahead of print.
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
COVID-19 generates hyaluronana fragments that directly induce endothelial barrier dysfunction. Queisser KA, Mellema RA, Middleton EA, Portier I, Manne BK, Denorme F, Beswick EJ et al. COVID-19 causes damage to the protective layer of lung cells, which could cause lung injury. JCI Insight. 2021 Sep 8;6(17):147472.
Tofacitinib therapy intercepts macrophage metabolic reprogramming instigated by SARS-CoV-2 spike protein. Palasiewicz K, Umar S, Romay B, Zomorrodi RK, Shaharara S. Tofacitinib suppresses inflammation and immunometabolism triggered by the SARS-CoV-2 spike protein and may provide a promising strategy for COVID-19 patients. Eur J Immunol. 2021 Sep;51(9):2330-2340.
Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome. Sulaiman I, Chung M, Angel L, Tsay JJ, Wu BG, Yeung ST, Krolikowski K et al. Secondary respiratory infections do not drive mortality in COVID-19. Nat Microbiol. 2021 Aug 31. Online ahead of print.
SARS-CoV-2 impairs dendritic cells and regulates DC-SIGN gene expression in tissues. Cai G, Du M Bosse Y, Albrecht H, Qin F, Luo X, Androulakis XM et al. The study provides insights into the profound modulation of dendritic cell function in severe COVID-19. Int J Mol Sci. 2021 Aug 26;22(17):9228.
Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19. van der Wijst MGP, Vazquez SE, Hartoularos GC, Bastard P, Grant T, Bueno R, Lee DS et al. A lack of gene expression for a specific type of antibody in patients with severe COVID-19 supports a unifying model of how COVID-19 progresses in the body. Sci Transl Med. 2021 Aug 24. Online ahead of print.
Data Analysis/Review
Accuracy of the Veterans Health Administration COVID-19 (VACO) Index for predicting short-term mortality among 1307 US academic medical centre inpatients and 427 224 US Medicare patients. King JT Jr, Yoon JS, Bredl ZM, Habboushe JP, Walker GA, Rentsch CT, Tate JP et al. The VACO Index could help inform vaccination prioritization and indicate who among outpatients testing positive for COVID-19 should receive greater clinical attention or scarce treatments. J Epidemiol Community Health. 2021 Sep 28. Online ahead of print.
Changes in activity levels, physical functioning, and fall risk during the COVID-19 pandemic. Hoffman GJ, Malani PN, Solway E, Kirch M, Singer DC, Kullgren JT. The COVID-19 pandemic was associated with worsened physical functioning and fall outcomes, with the greatest effect on individuals with reduced physical activity and social isolation. J Am Geriatr Soc. 2021 Sep 18. Online ahead of print.
Effectiveness of COVID-19 mRNA vaccines against COVID-19 associated hospitalizations – Five Veterans Affairs medical centers, United States, February 1-August 6, 2021. Bajema KL, Dahl RM, Prill MM, Meites E, Rodriguez-Barradas MC, Marconi VC, Beenhouwer DO et al. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated hospitalization. MMWR Morb Mortal Wkly Rep. 2021 Sep 17;70(37):1294-1299.
Early convalescent plasma therapy and mortality among US Veterans hospitalized with nonsevere COVID-19: An observational analysis emulating a target trial. Cho K, Keithly SC, Kurgansky KE, Madenci AL, Gerlovin H, Marucci-Willman H, Doubleday A et al. A targeted emulation estimated no meaningful differences in 30-day mortality between nonsevere COVID-19 patients treated and untreated with convalescent plasma. J Infect Dis. 2021 Sep 17;224(6):967-975.
Posttraumatic growth among health care workers on the frontlines of the COVID-19 pandemic. Feingold JH, Hurtado A, Feder A, Peccoralo L, Southwick SM, Ripp J, Pietrzak RH. Nearly four out of five frontline health care workers reported posttraumatic growth, driven largely by salutogenic factors assessed during the pandemic surge. J Affect Disord. 2021 Sep 16;296:35-40.
Other Research
Effectiveness of mRNA Covid-19 vaccine among U.S. health care personnel. Pilishvili T, Gierke R, Fleming-Dutra KE, Farrar JL, Mohr NM, Talan DA, Krishnadasan A et al. The mRNA vaccines were highly effective under real-world conditions in preventing symptomatic COVID-19 in health care personnel, including in those at risk for severe COVID-19 and those in racial and ethnic groups that have been disproportionally affected by the pandemic. N Eng J Med. 2021 Sep 22. Online ahead of print.
Machine-learning-based COVID-19 mortality prediction model and identification of patients at low and high risk of dying. Banoei MM, Dinparastisaleh R, Zadeh AV, Mirsaeidi M. Machine-learning approaches are able to predict hospital mortality in patients with COVID-19. Crit Care. 2021 Sep 8;25(1):328.
Comparison of antigen- and RT-PCR-based testing strategies for detection of SARS-CoV-2 in two high-exposure settings. Love J, Wimmer MT, Toth DJA, Chandran A, Makhija D, Cooper CK, Samore MH, Keegan LT. Antigen-based COVID-19 surveillance testing coupled with isolation greatly reduces disease burden and carries a lower cost than RT-PCR-based strategies. The two testing types perform different functions in reducing disease burden. PLoS One. 2021 Sep 7;16(9):e0253407.
COVID-19 related moral injury: Associations with pandemic-related perceived threat and risky and protective behaviors. Khan AJ, Nishimi K, Tripp P, Maven D, Jiha A, Woodward E, Inslicht S et al. Betrayal and transgression by others were associated with greater future threat of COVID-19 to health. Stronger endorsement of transgression by self was associated with more frequently engaging in risky behaviors for contracting COVID-19. J Psychiatr Res. 2021 Jul 22;142:80-88.
Anti-SARS-CoV-2 immune responses in patients receiving an allogeneic stem cell or organ transplant. Atanackovic D, Luetkens T, Avila SV, Hardy NM Lutfi F, Sanchez-Petitto G, Vander Mause E et al. Some organ or stem cell transplant patients are able to mount an anti-COVID-19 immune response. However, time between transplant and exposure may be necessary, some patients may lose acquired immunity after transplant, and some transplant patients may be unable to build an immune response. Vaccines (Basel) 2021 Jul 3;9(7):737.
Commentary
Suicide prevention in the COVID-19 era. Rothman S, Sher L. With the COVID-19 pandemic affecting mental health and creating social isolation, preventative measures need to be implemented universally. Prev Med. 2021 Nov;152(Pt 1):106547.
Addressing and inspiring vaccine confidence in Black, indigenous, and people of color during the coronavirus disease 2019 pandemic. Marcelin JR, Swartz TH, Bernice F, Berthaud V, Christian R, da Costa C, Fadul N et al. This article explores the impact of inequities on vaccine acceptance and ways to establish trustworthiness in health care institutions; increase vaccine access in minority communities; and inspire confidence in COVID-19 vaccines. Open Forum Infect Dis. 2021 Aug 0;8(9):ofab417.
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.
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.
