Effectiveness of mRNA COVID-19 Vaccine Boosters Against Infection, Hospitalization, and Death: A Target Trial Emulation in the Omicron (B.1.1.529) Variant Era

George N Ioannou, Amy S B Bohnert, Ann M O'Hare, Edward J Boyko, Matthew L Maciejewski, Valerie A Smith, C Barrett Bowling, Elizabeth Viglianti, Theodore J Iwashyna, Denise M Hynes, Kristin Berry, COVID-19 Observational Research Collaboratory (CORC), Pamela Green, Alexandra Fox, Anna Korpak, Troy Shahoumian, Alex Hickok, Mazhgan Rowneki, Xiao Qing Wang, Emily R Locke, George N Ioannou, Amy S B Bohnert, Ann M O'Hare, Edward J Boyko, Matthew L Maciejewski, Valerie A Smith, C Barrett Bowling, Elizabeth Viglianti, Theodore J Iwashyna, Denise M Hynes, Kristin Berry, COVID-19 Observational Research Collaboratory (CORC), Pamela Green, Alexandra Fox, Anna Korpak, Troy Shahoumian, Alex Hickok, Mazhgan Rowneki, Xiao Qing Wang, Emily R Locke

Abstract

Background: 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.

Objective: 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.

Design: 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.

Setting: U.S. Department of Veterans Affairs health care system.

Participants: Persons who had received 2 mRNA COVID-19 vaccine doses at least 5 months earlier.

Intervention: Booster monovalent mRNA vaccination (Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273) versus no booster.

Measurements: Booster VE.

Results: Each group included 490 838 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.

Limitation: Predominantly male population.

Conclusion: 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.

Primary funding source: U.S. Department of Veterans Affairs.

Conflict of interest statement

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-1856.

Figures

Visual Abstract.. Effectiveness of mRNA COVID-19 Vaccine…
Visual Abstract.. Effectiveness of mRNA COVID-19 Vaccine Boosters in the Omicron Variant Era.
This retrospective matched cohort study, which was designed to emulate a target trial of booster vaccination versus no booster, sought to determine mRNA booster vaccine effectiveness 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.
Figure 1.. Kaplan–Meier curves comparing persons who…
Figure 1.. Kaplan–Meier curves comparing persons who received a booster mRNA COVID-19 vaccine versus their matched counterparts who did not with respect to the cumulative incidence (percentage) and 95% CIs of SARS-CoV-2 infection (top) and SARS-CoV-2–related hospitalization (bottom).
Figure 2.. Kaplan–Meier curves comparing persons who…
Figure 2.. Kaplan–Meier curves comparing persons who received a booster mRNA COVID-19 vaccine versus their matched counterparts who did not with respect to the cumulative incidence (percentage) and 95% CIs of SARS-CoV-2–related death (top) and SARS-CoV-2 infection in the first 10 days after time zero (negative outcome control) (bottom).

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