LAUSR

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-HRadjusted) 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.