Abstract
The effectiveness of a third mRNA COVID-19 vaccine dose (booster dose) against the Omicron (B.1.1.529) variant is uncertain, especially in older, high-risk populations. To determine mRNA booster vaccine effectiveness (VE) against SARS-CoV-2 infection, hospitalization, and death in the Omicron era by booster type, primary vaccine type, time since primary vaccination, age, and comorbidity burden. Retrospective matched cohort study designed to emulate a target trial of booster vaccination versus no booster, conducted from 1 December 2021 to 31 March 2022. U.S. Department of Veterans Affairs health care system. Persons who had received 2 mRNA COVID-19 vaccine doses at least 5 months earlier. Booster monovalent mRNA vaccination (Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273) versus no booster. Booster VE. Each group included 490838 well-matched persons, who were predominantly male (88%), had a mean age of 63.0 years (SD, 14.0), and were followed for up to 121 days (mean, 79.8 days). Booster VE more than 10 days after a booster dose was 42.3% (95% CI, 40.6% to 43.9%) against SARS-CoV-2 infection, 53.3% (CI, 48.1% to 58.0%) against SARS-CoV-2-related hospitalization, and 79.1% (CI, 71.2% to 84.9%) against SARS-CoV-2-related death. Booster VE was similar for different booster types (BNT162b2 or mRNA-1273), age groups, and primary vaccination regimens but was significantly higher with longer time since primary vaccination and higher comorbidity burden. Predominantly male population. Booster mRNA vaccination was highly effective in preventing death and moderately effective in preventing infection and hospitalization for up to 4 months after administration in the Omicron era. Increased uptake of booster vaccination, which is currently suboptimal, should be pursued to limit the morbidity and mortality of SARS-CoV-2 infection, especially in persons with high comorbidity burden. U.S. Department of Veterans Affairs.
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