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 COVID-19 booster vaccines. We evaluated the relative effectiveness (rVE) of a primary series of mRNA-1273 versus BNT162b2 and Ad26.COV2.S and a homologous mRNA booster against medically-attended, outpatient, and hospitalized COVID-19. Methods A dataset linking primary care electronic medical records with medical claims data was used for this retrospective cohort study of US patients ≥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 (HR) were derived from 1:1 matching adjusted across potential covariates. rVE was (1-HR adjusted ) x 100. Additional analysis was performed across regions and age groups. Results Following adjustment, Part 1 rVE for mRNA-1273 versus BNT162b2 was 23% (95% CI: 22%–25%), 23% (22%–25%), and 19% (14%–24%) whilst the rVE for mRNA-1273 versus Ad26.COV2.S was 50% (48%–51%), 50% (48%–52%), and 57% (53%–61%) against any medically-attended, outpatient, and hospitalized COVID-19, respectively. The adjusted rVE in Part 2 for mRNA-1273 versus BNT162b2 was 14% (10%–18%), 13% (8%– 17%), and 19% (1%–34%) against any medically-attended, outpatient, and hospitalized COVID-19, respectively. rVE against medically-attended COVID-19 was higher in adults ≥65 years (35%; 24%–47%) than those 18–64 years (13%; 9%–17%) after the booster. Conclusions In this study, mRNA-1273 was more effective than BNT162b2 or Ad26.COV2.S following primary series during a Delta-dominant period, and than BNT162b2 as a booster during an Omicron-dominant period. Key points mRNA-1273 was associated with a lower risk than BNT162b2 or Ad26.COV2.S of any medically-attended, outpatient, or hospitalized COVID-19 after primary series and of any medically-attended, outpatient, or hospitalized COVID-19 vs BNT162b2 after a homologous mRNA booster