Late Mortality After COVID-19 Infection Among US Veterans vs Risk-Matched Comparators
Authors: Iwashyna Theodore J. , Seelye Sarah , Berkowitz Theodore S. , Pura John , Bohnert Amy S. B. , Bowling C. Barrett , Boyko Edward J. , Hynes Denise M. , Ioannou George N. , Maciejewski Matthew L. , O’Hare Ann M. , Viglianti Elizabeth M. , Womer James , Prescott Hallie C. , Smith Valerie A. ,   VA HSR&D COVID-19 Observational Research Collaboratory, Admon Andrew , Akgun Kathleen , Anderson Stacy , Aslan Mihaela , Au David , Backus Lisa , Bajema Kristina , Baraff Aaron , Batten Lisa , Berkowitz Theodore , Bernstein Taylor , Berry Wyatt Kristin , Bogdan Joseph , Bosworth Hayden , Boucher Nathan , Burwick Nicholas , Cabrales Aissa , Cano Jennifer , Chai Wen , Chen Jason , Cheung Kei-Hoi , Crothers Kristina , Curtis Jeffrey , Davis Marie , Del Monico Emily , Dobalian Aram , Doll Jacob , Dominitz Jason , Eastment McKenna , Fan Vincent , Ferguson Jacqueline , Floyd Breanna , Fox Alexandra , Goetz Matthew , Govier Diana , Green Pamela , Hastings Susan Nicole , Hauschildt Katie , Hawkins Eric , Hebert Paul , Helfand Mark , Hickok Alex , Horowitz Dana , Hough Catherine , Hu Elaine , Ikuta Kevin , Jones Barbara , Jones Makoto , Kamphuis Lee , Kaufman Brystana , Knight Sara , Korpak Anna , Korpela Peggy , Kumbier Kyle , Langa Kenneth , Laundry Ryan , Lavin Stacy , Li Yuli , Linquist Jennifer , McCready Holly , Michel Martha , Miles Amy , Milne Jessie , Monahan Max , Morelli Daniel , Mutalik Pradeep , Naylor Jennifer , Neiderhausen Meike , Newell Summer , Nugent Shannon , Ong Michael , Osborne Thomas , Peterson Matthew , Peterson Alexander , Rajeevan Nallakkandi , Reddy Ashok , Rouse Marylena , Rowneki Mazhgan , Saha Som , Saini Sameer , Shah Javeed , Shahoumian Troy , Shaukat Aasma , Shepherd-Banigan Megan , Showalter Whitney , Slatore Christopher , Smith Nicholas , Smith Battista , Suri Pardeep , Sussman Jeremy , Takata Yumie , Teo Alan , Thomas Eva , Thomas Laura , Tuepker Anais , Veigulis Zachary , Vig Elizabeth , Vranas Kelly , Wang Xiao Qing , Wicks Katrina , Winchell Kara , Wong Edwin , Woods Chris , Wysham Katherine , Yan Lei , Zulman Donna 
Published: August 2023

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.