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. 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.
2. 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 Aug 21.
3. 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, Reid MC. 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 6.
4. 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.
5. 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.
6. 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.
7. 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.
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.
9. 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.

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.