BACKGROUND/RATIONALE:
More than 600,000 Veterans have now been infected with SARS-CoV-2, and more than 20,000 Veterans have died from COVID-19 since the beginning of the pandemic. It is becoming increasingly clear that a subset of those infected with SARS-CoV-2 go on to experience a variety of long-term adverse health consequences.

OBJECTIVE(S):
The goal of the LTO Study is to understand the long-term health consequences of COVID-19 in the Veteran population. Because the long-term effects of SARS-CoV-2 are incompletely understood and because many Veterans have a high burden of comorbidity and debility, characterizing the long-term consequences of infection with SARS-CoV-2 in the Veteran population using observational data will require a sophisticated methodologic approach capable of supporting robust causal inference.

METHODS:
The COVID-19 Observational Research Collaboratory -LTO will use a variety of complementary research methodologies to understand the long-term consequences of infection with SARS-CoV-2: (1) We will use an emulated randomized controlled trial design based on VA-wide electronic health record (EHR) data to understand the relationship between viral infection and long-term mortality, health care use, and disease burden, including the development of new diagnoses. Designated infected and comparator groups based on analyses of EHR data will serve as the "backbone" for the other two components of the study described below; (2) We will conduct a prospective longitudinal survey among a stratified randomly sampled infected and comparator groups from the aforementioned EHR cohort in order to obtain information not readily available in health records to gain insight into the impact of SARS-CoV-2 infection on functional status, care needs and financial consequences (3) To understand the perspectives and experiences of Veterans pertaining to the long-term consequences of COVID-19, we will conduct semi-structured interviews with approximately 45 Veterans infected with SARS-CoV-2 that will be purposively sampled from the EHR cohort, including a subset of those who agree to participate in the survey. Interview recordings and transcripts will be analyzed qualitatively to identify emergent themes. We anticipate that insights gained from qualitative analysis will help to support hypothesis generation and to guide and refine our EHR and survey-based efforts.

FINDINGS/RESULTS:
In a manuscript under review at the JAMA Family of journals, we document a dramatic increase in the number of COVID re-infections confirmed by PCR among Veterans in December 2021 and January 2022 -- over 4,000 Veterans were confirmed reinfected in that later month.

IMPACT:
Provide a more complete and accurate understanding of the causal effects of infection with SARS-CoV-2 in the Veteran population and to provide novel insights on the long-term impact of infections for individual Veterans and for the VA health system.

PUBLICATIONS:

Journal Articles

1. Bohnert AS, Kumbier K, Rowneki M, Gupta A, Bajema K, Hynes DM, Viglianti E, O'Hare AM, Osborne T, Boyko EJ, Young-Xu Y, Iwashyna TJ, Maciejewski M, Schildhouse R, Dimcheff D, Ioannou GN. Adverse outcomes of SARS-CoV-2 infection with delta and omicron variants in vaccinated versus unvaccinated US veterans: retrospective cohort study. BMJ (Clinical research ed.). 2023 May 23; 381:e074521. [view]
2. Yan L, Streja E, Li Y, Rajeevan N, Rowneki M, Berry K, Hynes DM, Cunningham F, Huang GD, Aslan M, Ioannou GN, Bajema KL. Anti-SARS-CoV-2 Pharmacotherapies Among Nonhospitalized US Veterans, January 2022 to January 2023. JAMA Network Open. 2023 Aug 1; 6(8):e2331249. [view]
3. Robinson-Lane SG, Leggett AN, Johnson FU, Leonard N, Carmichael AG, Oxford G, Miah T, Wright JJ, Blok AC, Iwashyna TJ, Gonzalez R. Caregiving in the COVID-19 pandemic: Family adaptations following an intensive care unit hospitalisation. Journal of Clinical Nursing. 2022 Oct 19. [view]
4. Ioannou GN, Ferguson JM, O'Hare AM, Bohnert ASB, Backus LI, Boyko EJ, Osborne TF, Maciejewski ML, Bowling CB, Hynes DM, Iwashyna TJ, Saysana M, Green P, Berry K. Changes in the associations of race and rurality with SARS-CoV-2 infection, mortality, and case fatality in the United States from February 2020 to March 2021: A population-based cohort study. PLoS Medicine. 2021 Oct 1; 18(10):e1003807. [view]
5. O'Hare AM, Vig EK, Iwashyna TJ, Fox A, Taylor JS, Viglianti EM, Butler CR, Vranas KC, Helfand M, Tuepker A, Nugent SM, Winchell KA, Laundry RJ, Bowling CB, Hynes DM, Maciejewski ML, Bohnert ASB, Locke ER, Boyko EJ, Ioannou GN, VA COVID Observational Research Collaboratory (CORC). Complexity and Challenges of the Clinical Diagnosis and Management of Long COVID. JAMA Network Open. 2022 Nov 1; 5(11):e2240332. [view]
6. Admon AJ, Wander PL, Iwashyna TJ, Ioannou GN, Boyko EJ, Hynes DM, Bowling CB, Bohnert ASB, O'Hare AM, Smith VA, Pura J, Hebert PL, Wong ES, Niederhausen M, Maciejewski ML. Consensus elements for observational research on COVID-19-related long-term outcomes. Medicine. 2022 Nov 18; 101(46):e31248. [view]
7. Smith VA, Berkowitz TSZ, Hebert P, Wong ES, Niederhausen M, Pura JA, Berry K, Green P, Korpak A, Fox A, Baraff A, Hickok A, Shahoumian TA, Bohnert ASB, Hynes DM, Boyko EJ, Ioannou GN, Iwashyna TJ, Bowling CB, O'Hare AM, Maciejewski ML. Correction: Design and analysis of outcomes following SARS-CoV-2 infection in veterans. BMC medical research methodology. 2023 Aug 25; 23(1):194. [view]
8. Ioannou GN, Locke ER, O'Hare AM, Bohnert ASB, Boyko EJ, Hynes DM, Berry K. COVID-19 Vaccination Effectiveness Against Infection or Death in a National U.S. Health Care System : A Target Trial Emulation Study. Annals of internal medicine. 2022 Mar 1; 175(3):352-361. [view]
9. Smith VA, Berkowitz TSZ, Hebert P, Wong ES, Niederhausen M, Pura JA, Berry K, Green P, Korpak A, Fox A, Baraff A, Hickok A, Shahoumian TA, Bohnert ASB, Hynes DM, Boyko EJ, Ioannou GN, Iwashyna TJ, Bowling CB, O'Hare AM, Maciejewski ML. Design and analysis of outcomes following SARS-CoV-2 infection in veterans. BMC medical research methodology. 2023 Apr 4; 23(1):81. [view]
10. Bajema KL, Wang XQ, Hynes DM, Rowneki M, Hickok A, Cunningham F, Bohnert A, Boyko EJ, Iwashyna TJ, Maciejewski ML, Viglianti EM, Streja E, Yan L, Aslan M, Huang GD, Ioannou GN. Early Adoption of Anti-SARS-CoV-2 Pharmacotherapies Among US Veterans With Mild to Moderate COVID-19, January and February 2022. JAMA Network Open. 2022 Nov 1; 5(11):e2241434. [view]
11. Bajema KL, Berry K, Streja E, Rajeevan N, Li Y, Mutalik P, Yan L, Cunningham F, Hynes DM, Rowneki M, Bohnert A, Boyko EJ, Iwashyna TJ, Maciejewski ML, Osborne TF, Viglianti EM, Aslan M, Huang GD, Ioannou GN. Effectiveness of COVID-19 Treatment With Nirmatrelvir-Ritonavir or Molnupiravir Among U.S. Veterans: Target Trial Emulation Studies With One-Month and Six-Month Outcomes. Annals of internal medicine. 2023 Jun 1; 176(6):807-816. [view]
12. Ioannou GN, Bohnert ASB, O'Hare AM, Boyko EJ, Maciejewski ML, Smith VA, Bowling CB, Viglianti E, Iwashyna TJ, Hynes DM, Berry K, COVID-19 Observational Research Collaboratory (CORC). Effectiveness of mRNA COVID-19 Vaccine Boosters Against Infection, Hospitalization, and Death: A Target Trial Emulation in the Omicron (B.1.1.529) Variant Era. Annals of internal medicine. 2022 Dec 1; 175(12):1693-1706. [view]
13. Ioannou GN, Berry K, Rajeevan N, Li Y, Mutalik P, Yan L, Bui D, Cunningham F, Hynes DM, Rowneki M, Bohnert A, Boyko EJ, Iwashyna TJ, Maciejewski ML, Osborne TF, Viglianti EM, Aslan M, Huang GD, Bajema KL. Effectiveness of Nirmatrelvir-Ritonavir Against the Development of Post-COVID-19 Conditions Among U.S. Veterans : A Target Trial Emulation. Annals of internal medicine. 2023 Oct 31. [view]
14. Layton BA, Kaya D, Kelly C, Williamson KJ, Alegre D, Bachhuber SM, Banwarth PG, Bethel JW, Carter K, Dalziel BD, Dasenko M, Geniza M, George A, Girard AM, Haggerty R, Higley KA, Hynes DM, Lubchenco J, McLaughlin KR, Nieto FJ, Noakes A, Peterson M, Piemonti AD, Sanders JL, Tyler BM, Radniecki TS. Evaluation of a Wastewater-Based Epidemiological Approach to Estimate the Prevalence of SARS-CoV-2 Infections and the Detection of Viral Variants in Disparate Oregon Communities at City and Neighborhood Scales. Environmental Health Perspectives. 2022 Jun 1; 130(6):67010. [view]
15. Iwashyna TJ, Seelye S, Berkowitz TS, Pura J, Bohnert ASB, Bowling CB, Boyko EJ, Hynes DM, Ioannou GN, Maciejewski ML, O'Hare AM, Viglianti EM, Womer J, Prescott HC, Smith VA, VA HSR&D COVID-19 Observational Research Collaboratory. Late Mortality After COVID-19 Infection Among US Veterans vs Risk-Matched Comparators: A 2-Year Cohort Analysis. JAMA internal medicine. 2023 Oct 1; 183(10):1111-1119. [view]
16. Ioannou GN, Baraff A, Fox A, Shahoumian T, Hickok A, O'Hare AM, Bohnert ASB, Boyko EJ, Maciejewski ML, Bowling CB, Viglianti E, Iwashyna TJ, Hynes DM. Rates and Factors Associated With Documentation of Diagnostic Codes for Long COVID in the National Veterans Affairs Health Care System. JAMA Network Open. 2022 Jul 1; 5(7):e2224359. [view]
17. Bajema KL, Rowneki M, Berry K, Bohnert A, Bowling CB, Boyko EJ, Iwashyna TJ, Maciejewski ML, O'Hare AM, Osborne TF, Viglianti EM, Hynes DM, Ioannou GN. Rates of and Factors Associated With Primary and Booster COVID-19 Vaccine Receipt by US Veterans, December 2020 to June 2022. JAMA Network Open. 2023 Feb 1; 6(2):e2254387. [view]
18. Hynes DM, Niederhausen M, Chen JI, Shahoumian TA, Rowneki M, Hickok A, Shepherd-Banigan M, Hawkins EJ, Naylor J, Teo A, Govier DJ, Berry K, McCready H, Osborne TF, Wong E, Hebert PL, Smith VA, Bowling CB, Boyko EJ, Ioannou GN, Iwashyna TJ, Maciejewski ML, O'Hare AM, Viglianti EM, Bohnert AS. Risk of Suicide-Related Outcomes After SARS-COV-2 Infection: Results from a Nationwide Observational Matched Cohort of US Veterans. Journal of general internal medicine. 2023 Oct 26. [view]

JPRE

1. Bajema KL, Berry K, Streja E, Rajeevan N, Li Y, Yan L, Cunningham F, Hynes DM, Rowneki M, Bohnert A, Boyko EJ, Iwashyna TJ, Maciejewski ML, Osborne TF, Viglianti EM, Aslan M, Huang GD, Ioannou GN. Effectiveness of COVID-19 treatment with nirmatrelvir-ritonavir or molnupiravir among U.S. Veterans: target trial emulation studies with one-month and six-month outcomes. medRxiv : the preprint server for health sciences [Preprint]. 2022 Dec 16. [view]