Relative Effectiveness of BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines and Homologous Boosting in Preventing COVID-19 in Adults in the US.

Background: Few head-to-head comparisons have been performed on the real-world effectiveness of coronavirus disease 2019 (COVID-19) booster vaccines. We evaluated the relative effectiveness (rVE) of a primary series of mRNA-1273 vs BNT162b2 and Ad26.COV2.S and a homologous mRNA booster against any medically attended, outpatient, and hospitalized COVID-19. Methods: A data set linking primary care electronic medical records with medical claims data was used for this retrospective cohort study of US patients age ≥18 years vaccinated with a primary series between February and October 2021 (Part 1) and a homologous mRNA booster between October 2021 and January 2022 (Part 2). Adjusted hazard ratios (HRs) were derived from 1:1 matching adjusted across potential covariates. rVE was (1 - HR Results: Following adjustment, Part 1 rVE for mRNA-1273 vs BNT162b2 was 23% (95% CI, 22%-25%), 23% (95% CI, 22%-25%), and 19% (95% CI, 14%-24%), while the rVE for mRNA-1273 vs Ad26.COV2.S was 50% (95% CI, 48%-51%), 50% (95% CI, 48%-52%), and 57% (95% CI, 53%-61%) against any medically attended, outpatient, and hospitalized COVID-19, respectively. The adjusted rVE in Part 2 for mRNA-1273 vs BNT162b2 was 14% (95% CI, 10%-18%), 13% (95% CI, 8%-17%), and 19% (95% CI, 1%-34%) against any medically attended, outpatient, and hospitalized COVID-19, respectively. rVE against medically attended COVID-19 was higher in adults age ≥65 years (35%; 95% CI, 24%-47%) than in those age 18-64 years (13%; 95% CI, 9%-17%) after the booster. Conclusions: In this study, mRNA-1273 was more effective than BNT162b2 or Ad26.COV2.S following a primary series during the Delta-dominant period and more effective than BNT162b2 as a booster during the Omicron-dominant period.