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 focused on establishing and taking part in clinical trials and data analysis projects aimed at understanding and treating the disease. VA Research has coordinated closely with internal VA and external partners—such as 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.
VA Research has taken these actions while working to ensure and promote the safety and well-being of all those involved in research. The program has also been enabling continuity of operations to the extent possible across the entire VA research portfolio, all of which is aimed at improving Veterans’ lives.
On this web page, we summarize key COVID-19 research activities currently underway across the VA system, and provide background information on how the VA Office of Research and Development has rapidly mobilized the nationwide VA research community and resources to contribute to the national response to the pandemic. The information below is current as of June 3, 2020, and will be updated regularly.
Below are examples of COVID-19 research underway in VA.
- Testing prostate cancer drug—VA is funding a phase 2 clinical trial exploring whether degarelix, a treatment used in prostate cancer, may be effective reducing the time to improved clinical outcomes.
- Trials with industry—VA is taking part in a number of industry-sponsored studies of promising medications for COVID-19. These include, 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 are taking 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 Emerging Infectious Diseases with Pandemic Potential” (EPICC-EID). The study will contribute to a better understanding of COVID-19.
Data analysis projects
- 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 VA’s Evidence Synthesis Program are working with the World Health Organization and the VA RAPID/biosurveillance group to help synthesize publications about the novel coronavirus and COVID-19, and to translate that information into usable guidance for clinicians. Recent ESP rapid reports in this area include: “Risk of Transmitting COVID-19 During Nebulizer Treatment”; “Intensive Care Unit Length of Stay and Ventilation Days”; and “Corticosteroid Therapy & ARDS for COVID-19 Infection.” More are in the works. These reports can be found at www.covid19reviews.org.
- 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.
- Examining off-label use of existing approved drugs— Drugs that are already FDA-approved for other health conditions are being used to treat COVID-19. VA Research is contributing to the understanding of whether these drugs are safe and useful by helping to track data on prescriptions, side effects, and outcomes; and working with VHA Public Health Surveillance and Research and Pharmacy Benefits Management on longitudinal tracking of data on COVID-19 patients, including those prescribed off-label drugs.
- 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
- Facilitating access to investigational drugs under the FDA’s expanded access, or “compassionate use,” program—VA Research has streamlined and organized a central assistance process for VA medical centers seeking expanded access (a.k.a. compassionate use) under FDA rules to investigational drugs for COVID-19 treatments. One treatment being used under this program is transfusions of blood plasma from patients who have recovered from COVID-19. This “convalescent” plasma contains antibodies that researchers believe may help other patients.
Selected Scientific Articles by VA Researchers
COVID-19, mast cells, cytokine storm, psychological stress, and neuroinflammation. Kempuraj D, Selvakumar GP, Ahmed ME, Raikwar SP, Thangavel R, Khan A, Zaheer SA, Iver SS, Burton C, James D, Zaheer A. COVID-19 can induce mast cell activation, psychological stress, cytokine storm, and neuroinflammation. Neuroscientist. 2020 Jul 10. Online ahead of print.
Review of viral testing (polymerase chain reaction) and antibody/serology testing for severe acute respiratory syndrome-coronavirus-2 for the intensivist. Motley MP, Bennett-Guerrero, Fries BC, Spitzer ED. This review details the strengths and weaknesses of various testing methods for the SARS-CoV-2 virus. Crit Care Explor. 2020 Jun 15;2(6):e0154.
Financial strain and risk of suicide in the wake of the COVID-19 pandemic. Elbogen EB, Lanier M, Montgomery AE, Strickland S, Wagner HR, Tsai J. The current pandemic and the financial strains it causes foreshadow a spike in suicide in upcoming months and years. Am J Epidemiol. 2020 Jul 22. Online ahead of print.
Clinical outcomes in COVID-19 patients treated with tocilizumab: An individual patient data systematic review. Antwi-Amoabeng D, Kanji Z, Ford B, Beutler BD, Riddle MS, Siddiqui F. Following tocilizumab treatment in COVID-19 patients, interleukin-6 levels elevate and C-reactive protein levels dramatically decrease, suggestion an improvement in the hyperinflammatory state. J Med Virol. 2020 May 21. Online ahead of print.
Evaluation of an electrostatic spray disinfectant technology for rapid decontamination of portable equipment and large open areas in the era of SARS-CoV-2. Cadnum JL, Jencson AL, Livingston SH, Li DF, Redmond SN, Pearlmutter B, Wilson BM, Donskey CJ. Wheelchairs, portable equipment, and waiting room chairs are frequently contaminated with potential pathogens. Application of a dilute sodium hypochlorite disinfectant using an electrostatic sprayer provided rapid and effective decontamination and eliminated the benign virus bacteriophage MS2 from inoculate surfaces. Am J Infect Control. 2020 Jun 6. Online ahead of print.
Evaluation of ultraviolet-C light for rapid decontamination of airport security bins in the era of SARS-CoV-2. Cadnum JL, Li DF, Jones LD, Redmond SN, Pearlmutter B, Wilson BM, Donskey CJ. UV-C light administered in proximity to a plastic bin reduced contamination. Pathog Immun. 2020 May 22;5(1):133-142.
A case for targeting Th17 cells and IL-17A in SARS-CoV-2. Orlov M, Wander PL, Morrell ED, Mikacenic C, Wurfel MM. This review describes evidence linking risk factors for critical illness in COVID-19 with increased Th17 cell activation and IL-17 signaling that may lead to increased likelihood for lung injury and respiratory failure. J Immunol. 2020 July 10. Online ahead of print.
National geriatric network rapidly addresses trainee telehealth needs in response to COVID-19. Nearing KA, Lum HD, Dang S, Powers B, McLaren J, Gately M, Hung W, Moo L. The Veterans Health Administration rapidly identified and responded to telehealth training needs of geriatrics trainees to optimize care for rural older adults as part of a rapid response to COVID-19. J AM Geriatr Soc. 2020 Jul 8. Online ahead of print.
Investigation of nosocomial SARS-CoV-2 transmission from two patients to health care workers identifies close contact but not airborne transmission events. Bays DJ, Nguyen MH, Cohen SH, Waldman S, Martin CS, Thompson GR, Sandrock C, Tourtellotte J, Pugashetti JV, Phan C, Nguyen HH, Warner GY, Penn BH. At least in a health care setting, a majority of SARS-CoV-2 transmission is likely to take place during close contact with infected patients through respiratory droplets, rather than by long-distance airborne transmission. Infect Control Hosp Epidemiol. 2020 Jul 3:1-22.
Combating heightened social isolation of nursing home elders: The Telephone Outreach in the COVID-19 Outbreak program. Van Dyck LI, Wilkins KM, Ouellet J, Ouellet GM, Conroy ML. A telephone outreach program achieved initial success and promotes the social well-being of nursing home residents. Am J Geriatr Psychiatry. 2020 Jun 5;S1064-7481(20)30365-1.
Use of baricitinib in patients with moderate and severe COVID-19. Titanji BK, Farley MM, Mehta A, Connor-Schuler R, Moanna A, Cribbs SK, O’Shea J, DeSilva K, Chan B, Edwards A, Gavegnano C, Schinazi RF, Marconi VC. In a small uncontrolled cohort of patients with moderate-severe COVID-19, treatment with baricitinib plus hydroxychloroquine was associated with recovery. Clin Infect Dis. 2020 Jun 29. Online ahead of print.
Differences in race and other state-level characteristics and associations with mortality from COVID-19 infection. Sehra ST, Fundin S, Lavery C, Baker JF. States with a greater proportion of African American residents report a higher death rate from COVID-19 despite adjusting for case rates and state-level factors. J Med Virol. 2020 May 30. Online ahead of print.
Recovery unit in a Veterans Affairs (VA) post-acute facility. Sohn L, Lysaght M, Schwartzman WA, Simon SR, Goetz MB, Yoshikawa T. J AM Geriatr Soc. 2020 Jun 18. Online ahead of print.
A model for treating COVID-19-related guilt, shame, and moral injury. Haller M, Norman SB, Davis BC, Capone C, Browne K, Allard CB. Trauma-informed guilt reduction therapy is a brief intervention that helps people accurately appraise their role in a stressful event, such as those experienced during the COVID-19 pandemic, and find positive ways to express important values going forward. Psychol Trauma. 2020 Jun 18. Online ahead of print.
Potential novel role of COVID-19 in Alzheimer’s disease and preventative mitigation strategies. Naughton SX, Raval U, Pasinetti GM. J Genetic and socioeconomic factors influencing the rates of Type 2 diabetes, Alzheimer’s disease, and COVID-19 severity may create an exceptionally high-risk profile for certain demographics. Alzheimers Dis. 2020 June 12. Online ahead of print.
Global impact of the COVID-19 pandemic on endoscopy: An international survey of 252 centers from 55 countries. Parasa S, Reddy N, Faigel DO, Repici A, Emura F, Sharma P. A substantial reduction in endoscopy procedures has been noted globally in light of the COVID-19 pandemic. Gastroenterology. 2020 June 11. Online ahead of print.
Mental health ramifications of the COVID-19 pandemic for Black Americans: Clinical and research recommendations. Novacek DM, Hampton-Anderson JN, Ebor MT, Loeb TB, Wyatt GE. Race-conscious and culturally competent interventions that consider factors such as discrimination, distrust of health care providers, and historical and racial trauma as well as protective factors including social support and culturally sanctioned coping strategies are needed. Psychol Trauma. 2020 Jun 11. Online ahead of print.
Aging veterans’ mental health and well-being in the context of COVID-19: The importance of social ties during physical distancing. Marini CM, Pless Kaiser A, Smith BN, Fiori KL. During the COVID-19 pandemic, aging Veterans may benefit from having an array of socially supportive network ties. Psychol Trauma. 2020 June 11. Online ahead of print.
Toward nanotechnology-enabled approaches against the COVID-19 pandemic. Weiss C, Carriere M, Fusco L, Capua I, Regla-Nava JA, Pasquali M, Scott JA, Vitale F, Unal MA, Matteyi C, Bedognetti D, Tascotti E, Yilmazer A, Gogotsi Y, Stellacci F, Delogu LG. Nanotechnology is critical in counteracting COVID-19 and will be vital when preparing for future pandemics. ACS Nano. 2020 June 10. Online ahead of print.
Coronavirus disease 2019 (COVID-19) catheterization laboratory survey. Banerjee S, Tarantini G, Abu-Fadel M, Banerjee A, Little BB, Sorajja P, Shishehbor MH, Brilakis ES. Invasive heart procedure rates have reduced significantly. There is near universal adoption of personal protective equipment; however, COVID-19 pretesting and access to N95 masks is suboptimal. J Am Heart Assoc. 2020 Jun 9;e017175. Online ahead of print.
Systematic review and meta-analysis on the value of chest CT in the diagnosis of coronavirus disease (COVID-19): Sol Scientiae, Illustra Nos. Adams HJA, Kwee TC, Yakar D, Hope MD, Kwee RM. Chest CT scans have relatively high sensitivity to infections in patients with COVID-19 symptoms, but studies on the testing suffer from quality issues. AJR Am J Roentgenol. 2020 Jun 1;1-9. Online ahead of print.
Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies. Gupta S, Singh AK, Kushwaha PP, Prajapati KS, Shuaib M, Senapti S, Kumar S. A protein was identified that may be an effective drug target for future COVID-19 treatments. J Biomol Struct Dyn. 2020 Jun 1:1-19. Online ahead of print.
Veterans’ response to an automated text messaging protocol during the COVID-19 pandemic. Saleem JJ, Read JM, Loehr BM, Frisbee KL, Wilck NR, Murphy JJ, Vetter BM, Herout J. Veterans responded well to automated text messaging about COVID-19 from the VA app “Annie.” J Am Med Inform Assoc. 2020 May 29. Online ahead of print.
Flattening the curve by getting ahead of it: How the VA healthcare system is leveraging telehealth to provide continued access to care for rural Veterans. Myers US, Birks A, Grubaugh AL, Axon RN. The rapid expansion of telehealth in response to COVID-19 within VHA and subsequent refinements to the system can be used to more immediately improve the health and well-being of Veterans facing ongoing access to care barriers, such as those residing in rural areas. J Rural Health. 2020 Apr 13;10. Online ahead of print.
Preventing suicide in rural communities during the COVID-19 pandemic. Monteith LL, Holliday R, Brown TL, Brenner LA, Mohatt NV. Individuals in rural communities may be disproportionately impacted by the COVID-19 pandemic. Ensuring that rural communities are adequately equipped to prevent suicide while managing the spread and impact of COVID-19 is critical. J Rural Health. 2020 May 30. Online ahead of print.
Survival after in-hospital cardiac arrest in critically ill patients: Implication for Covid-19 outbreak? Girotra S, Tang Y, Chan PS, Nallamothu BK. In a cohort of critically ill patients on mechanical ventilation, survival outcomes following in-hospital resuscitation were not uniformly poor. Circ Cardiovasc Qual Outcomes. 2020 May 22. Online ahead of print.
Challenges in the interpretation and application of typical imaging features of COVID-19. Hammer MM, Raptis CA, Henry TS, Shah A, Bhalla S, Hope MD. CT remains a powerful diagnostic tool in the context of COVID-19 and should be used to trouble-shoot problematic cases. Lancet Respir Med. 2020 Jun;8(6):534-536.
Mitigating the effects of a pandemic: Facilitating improved nursing home care deliver through technology. Edelman LS, McConnell E, Kennerly SM, Alderden J, Horn SD, Yap TL. Investing in and adapting technology can help mitigate workforce stress and improve the quality of nursing home care during and after the COVID-19 pandemic. JMIR Nursing. 2020 May 26;3(1):e20110.
TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Zang R, Gomez Castro MF, McCune BT, Zeng Q, Rothlauf PW, Sonnek NM, Liu Z, Brulois KF, Wang X, Greenberg HB, Diamond MS, Ciorba MA, Whelan SPJ, Ding S. The intestine is a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression. Sci Immunol. 2020 May 13;5(47):eabc3582.
AGA Institute rapid review of the GI and liver manifestations of COVID-19, meta-analysis of international data, and recommendations for the consultative management of patients with COVID-19. Sultan S, Altayar O, Siddique SM, Davitkoy P, Feuerstein JD, Lim JK, Falck-Ytter Y, El-Serag HB. Gastrointestinal symptoms are associated with COVID-19 in less than 10% of patients. Further studies are needed with standardized GI symptoms questionnaires. Gastroenterology. 2020 May 11;S0016-5085(20)30593-X.
Chloroquine and hydroxychloroquine in the context of COVID-19. Shukla AM, Archibald LK, Shukla AW, Mehta HJ, Cherabuddi K. Pending the availability of confirmatory studies, the use of chloroquine and hydroxychloroquine in COVID-19 should be viewed as experimental at this stage, and it should adhere to local, regional, or national ethics and research guidelines. Drugs Context. 2020 Apr 28;9:2020-4-5.
Department of Veterans Affairs Public Health
Centers for Disease Control and Prevention
COVID-19 Reviews [maintained by VA ESP]
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.