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. 2023 Oct 1;183(10):1111-1119.
doi: 10.1001/jamainternmed.2023.3587.

Late Mortality After COVID-19 Infection Among US Veterans vs Risk-Matched Comparators: A 2-Year Cohort Analysis

Theodore J Iwashyna  1   2   3   4 , Sarah Seelye  1 , Theodore S Berkowitz  5 , John Pura  5 , Amy S B Bohnert  1   6 , C Barrett Bowling  5   7   8 , Edward J Boyko  9   10 , Denise M Hynes  11   12   13 , George N Ioannou  9   10 , Matthew L Maciejewski  5   8   14 , Ann M O'Hare  9   10 , Elizabeth M Viglianti  1   2 , James Womer  3 , Hallie C Prescott  1   2 , Valerie A Smith  5   8   14 ; VA HSR&D COVID-19 Observational Research Collaboratory
Collaborators, Affiliations

Late Mortality After COVID-19 Infection Among US Veterans vs Risk-Matched Comparators: A 2-Year Cohort Analysis

Theodore J Iwashyna et al. JAMA Intern Med. .

Erratum in

  • Error in Nonauthor Collaborator Supplement.
    [No authors listed] [No authors listed] JAMA Intern Med. 2024 Apr 1;184(4):453. doi: 10.1001/jamainternmed.2023.8594. JAMA Intern Med. 2024. PMID: 38315461 Free PMC article. No abstract available.

Abstract

Importance: Despite growing evidence of persistent problems after acute COVID-19, how long the excess mortality risk associated with COVID-19 persists is unknown.

Objective: To measure the time course of differential mortality among Veterans who had a first-documented COVID-19 infection by separately assessing acute mortality from later mortality among matched groups with infected and uninfected individuals who survived and were uncensored at the start of each period.

Design, settings, and participants: This retrospective cohort study used prospectively collected health record data from Veterans Affairs hospitals across the US on Veterans who had COVID-19 between March 2020 and April 2021. Each individual was matched with up to 5 comparators who had not been infected with COVID-19 at the time of matching. This match balanced, on a month-by-month basis, the risk of developing COVID-19 using 37 variables measured in the 24 months before the date of the infection or match. A primary analysis censored comparators when they developed COVID-19 with inverse probability of censoring weighting in Cox regression. A secondary analysis did not censor. Data analyses were performed from April 2021 through June 2023.

Exposure: First-documented case of COVID-19 (SARS-CoV-2) infection.

Main outcome measures: Hazard ratios for all-cause mortality at clinically meaningful intervals after infection: 0 to 90, 91 to 180, 181 to 365, and 366 to 730 days.

Results: The study sample comprised 208 061 Veterans with first-documented COVID-19 infection (mean [SD] age, 60.5 (16.2) years; 21 936 (10.5) women; 47 645 [22.9] Black and 139 604 [67.1] White individuals) and 1 037 423 matched uninfected comparators with similar characteristics. Veterans with COVID-19 had an unadjusted mortality rate of 8.7% during the 2-year period after the initial infection compared with 4.1% among uninfected comparators, with censoring if the comparator later developed COVID-19-an adjusted hazard ratio (aHR) of 2.01 (95% CI, 1.98-2.04). The risk of excess death varied, being highest during days 0 to 90 after infection (aHR, 6.36; 95% CI, 6.20-6.51) and still elevated during days 91 to 180 (aHR, 1.18; 95% CI, 1.12-1.23). Those who survived COVID-19 had decreased mortality on days 181 to 365 (aHR, 0.92; 95% CI, 0.89-0.95) and 366 to 730 (aHR, 0.89; 95% CI, 0.85-0.92). These patterns were consistent across sensitivity analyses.

Conclusion and relevance: The findings of this retrospective cohort study indicate that although overall 2-year mortality risk was worse among those infected with COVID-19, by day 180 after infection they had no excess mortality during the next 1.5 years.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Iwashyna reported grants from US Department of Veterans Affairs (VA) Health Services Research and Development (HSR&D) during the conduct of the study and grants from the US National Institutes of Health outside the submitted work. Dr Seelye reported grants from HSR&D during the conduct of the study; and grants from HSR&D and the Agency for Healthcare Research and Quality outside the submitted work. Mr Berkowitz reported support from the Durham Center of Innovation to Accelerate Discovery and Practice Transformation (No. CIN 13-410) during the conduct of this study. Dr Boyko reported personal fees from the Korean Diabetes Association and from the Diabetes Association of the Republic of China (Taiwan) outside the submitted work. Dr Hynes reported grants from VA Office of Research & Development (ORD) HSR&D Service (Nos. SDR 21-279, C-19-20-208, and RCS-21-136) during the conduct of the study; grants from VA ORD HSR&D Service (Nos. IIR-20-165 SDR 30-390, RVR 19-481, SDR-18-321, IIR-18-093), Pacific Source Community Services, the David and Lucille Packard Foundation, and the University of North Carolina Chapel Hill (a Patient-Centered Outcomes Research Institute award for Oregon State University); personal fees from QualityInsights; scientific consulting and co-ownership of van Breemen & Hynes; and , all outside the submitted work. Dr Maciejewski reported equity in Amgen outside the submitted work. Dr O’Hare reported grants from VA Puget Sound Health Care System HSR&D during the conduct of the study. Dr Viglianti reported grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Prescott reported grants from the US Centers for Disease Control and Prevention, Blue Cross Blue Shield of Michigan, US National Institutes of Health, and the Agency for Healthcare Research and Quality, all outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Overall and Time Since Infection-Specific Mortality, From With Censoring, Unweighted Approach
Figure panels C, D, and E have different y-axis scaling to allow for clearer interpretation.
See this image and copyright information in PMC

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