Late Mortality After COVID-19 Infection Among US Veterans vs Risk-Matched Comparators

Abstract

ImportanceDespite growing evidence of persistent problems after acute COVID-19, how long the excess mortality risk associated with COVID-19 persists is unknown.ObjectiveTo 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 ParticipantsThis 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.ExposureFirst-documented case of COVID-19 (SARS-CoV-2) infection.Main Outcome MeasuresHazard 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.ResultsThe 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 RelevanceThe 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.

Self-Reported Everyday Functioning After COVID-19 Infection

“…Because our data were collected via survey, we did not include individuals who had died, which may violate target trial emulation conditioned on postrandomization information. 27 We have previously measured that the population-weighted differences in mortality, 25 which could introduce censoring of the extreme phenotype bias. 31 Our study was further limited by the small sample size, which was partially due to a lower-than-expected recruitment rate, which has been seen in other studies.…”

“…We present analyses among individuals with a history of COVID-19 infection who were alive 18 months after onset and did not adjust for death in these estimates, as mortality analyses have been published separately. 25 To assess robustness, we also reanalyzed the outcomes without applying weights and, separately analyzed the outcomes without removing any individuals with a history of COVID-19 prior to survey. We also conducted hypothesis-generating post hoc analyses 26 , 27 separately by whether or not the COVID-19 cohort was hospitalized within 7 days of their first positive test.…”

Cause-Specific Excess Mortality in the US During the COVID-19 Pandemic

“…Early estimates of US excess mortality were higher than official COVID-19 deaths 2,3 , suggesting undercounted COVID-19 mortality and/or increases in other causes of death during the pandemic. COVID-19 may also have longer-term impacts on mortality risk after acute infection or due to disruptions in health care delivery, resulting in persistent excess mortality 4 .…”

One-Year Mortality and Associated Factors in Older Hospitalized COVID-19 Survivors: A Nationwide Cohort Study in Korea

“…The enduring impact of COVID-19 extends beyond physical and mental health issues to include increased mortality. Iwashyna et al found that individuals who had contracted COVID-19 faced a twofold increase in mortality risk within 2 years compared to those not infected with SARS-CoV-2 5 . The risk of long-term mortality is affected by factors such as age and the severity of the SARS-CoV-2 infection 6,7 .…”