COVID-19 Infection Not Associated with Clinically Significant Excess Mortality among Veterans Surviving at Least 180 Days

BACKGROUND:
It is unclear whether survivors of COVID-19 experience excess mortality after acute infection and, if so, how long any excess mortality persists. This retrospective cohort study compared the time course of differential mortality among Veterans who had a first-documented COVID-19 infection between March 2020 and April 2021, and were followed through April 2022. Investigators separately evaluated acute mortality (e.g., on days 0-90 after infection) and later mortality (i.e., on days 181-365 and days 366-730) among matched groups of infected (n = 208,061) and uninfected Veterans (n = 1,037,423) who had survived to the beginning of the respective period. The VA COVID-19 Shared Data Resource (VA network access only) database was used to identify Veterans with COVID-19. Each Veteran with COVID-19 was matched with up to five comparators who had not been infected 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.

FINDINGS:

• Although overall 2-year mortality risk was worse among those infected with COVID-19, by day 180 after infection Veterans on average had no excess mortality over the next 1.5 years. Thus, despite growing evidence of persistent risks after acute COVID-19, the excess mortality risk associated with COVID-19 did not persist as long as expected.
• Veterans with COVID-19 had an unadjusted mortality rate of 9% during the 2-year period after the initial infection compared with 4% among uninfected comparators, which suggests an excess of 9,625 deaths among infected Veterans.
• The risk of excess death varied, being highest during days 0 to 90 after infection and remaining elevated during days 91 to 180. On average, those who survived COVID-19 had modestly decreased mortality on days 181 to 365 and days 366 to 730.
• Veterans hospitalized for COVID-19 experienced increased mortality at all time periods through 730 days post-infection, so resolution of excess mortality risk was driven by the non-hospitalized subset.

IMPLICATIONS:

• For ongoing clinical care after COVID-19, efforts that focus on improving survival outcomes may be less relevant than addressing the needs of survivors, particularly those not initially hospitalized.

LIMITATIONS:

• Only up to 24 months of follow-up had accrued for Veterans who became infected in March 2020 through April 2021, so results should not be generalized to Veterans who became infected with more recent variants of COVID-19.
• The potential cumulative effects of COVID-19 will not be fully seen for years or decades to come, therefore, these data suggest ongoing differences for which follow-up is needed.

AUTHOR/FUNDING INFORMATION:
This study was supported by HSR&D. Drs. Iwashyna and Seelye are part of HSR&D’s Center for Clinical Management Research (CCMR) and Mr. Berkowitz is with HSR&D’s Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT).

: Iwashyna T, Seelye S, Berkowitz T, et al., for the VA HSR&D COVID-19 Observational Research Collaboratory (CORC). Late Mortality after COVID-19 Infection among US Veterans vs Risk-Matched Comparators: A 2-Year Cohort Analysis. JAMA Internal Medicine. August 21, 2023; online ahead of print.