Early Mortality After the First Dose of COVID-19 Vaccination: A Target Trial Emulation.

Background: Vaccine hesitancy persists alongside concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines. We aimed to examine the effect of COVID-19 vaccination on risk of death among US veterans.
Methods: We conducted a target trial emulation to estimate and compare risk of death up to 60 days under two COVID-19 vaccination strategies: vaccination within 7 days of enrollment versus no vaccination through follow-up. The study cohort included individuals aged ≥18 years enrolled in the Veterans Health Administration system and eligible to receive a COVID-19 vaccination according to guideline recommendations from 1 March 2021 through 1 July 2021. The outcomes of interest included deaths from any cause and excluding a COVID-19 diagnosis. Observations were cloned to both treatment strategies, censored, and weighted to estimate per-protocol effects.
Results: We included 3 158 507 veterans. Under the vaccination strategy, 364 993 received vaccine within 7 days. At 60 days, there were 156 deaths per 100 000 veterans under the vaccination strategy versus 185 deaths under the no vaccination strategy, corresponding to an absolute risk difference of -25.9 (95% confidence limit [CL], -59.5 to 2.7) and relative risk of 0.86 (95% CL, .7 to 1.0). When those with a COVID-19 infection in the first 60 days were censored, the absolute risk difference was -20.6 (95% CL, -53.4 to 16.0) with a relative risk of 0.88 (95% CL, .7 to 1.1).
Conclusions: Vaccination against COVID-19 was associated with a lower but not statistically significantly different risk of death in the first 60 days. These results agree with prior scientific knowledge suggesting vaccination is safe with the potential for substantial health benefits.
Competing Interests: Potential conflicts of interest. K. W. M., S. G., and A. R. Z. report investigator-initiated support from Sanofi, Seqirus, and Pfizer for other non–coronavirus disease 2019 (COVID-19) vaccine-related work. I. J. D. is principal investigator of a research agreement between Sanofi and Harvard University to develop methods for transportability analyses for use of influenza vaccination trials and reports consulting fees from ModernaTX for work unrelated to COVID-19. S.G. reports vaccine related consulting or speaker fees from GlaxoSmithKline, Janssen, Moderna, Novavax, Pfizer, Sanofi, Seqirus. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)