Comparative Effectiveness of the Bivalent (Original/Omicron BA.4/BA.5) mRNA COVID-19 Vaccines mRNA-1273.222 and BNT162b2 Bivalent in Adults With Underlying Medical Conditions in the United States

This retrospective cohort study evaluated the relative vaccine effectiveness (rVE) of two bivalent (Original/Omicron BA.4/BA.5) vaccines mRNA-1273.222 versus BNT162b2 Bivalent in preventing COVID-19-related outcomes in adults with underlying medical conditions associated with increased risk for severe COVID-19. In a linked EHR-claims dataset, US adults (≥ 18 years) with ≥ 1 underlying medical condition of interest who received either bivalent vaccine between August 31, 2022, and February 28, 2023, were identified. Inverse probability of treatment weighting was used to adjust for cohort differences. Cohorts were followed up for COVID-19-related hospitalizations and outpatient encounters until May 31, 2023. Hazard ratios and rVEs were estimated using Cox regression. Subgroup analyses were performed on individuals with pre-specified comorbid conditions. 757,572 mRNA-1273.222 and 1,204,975 BNT162b2 Bivalent recipients were identified. The adjusted rVE over a median follow-up of 198 days was 10.9% (6.2%-15.2%) against COVID-19-related hospitalization and 3.2% (1.7%-4.7%) against COVID-19-related outpatient encounters. rVE estimates for COVID-19 hospitalizations among subgroups with comorbid conditions were: diabetes 15.1% (8.7%-21.0%), cardiovascular disease 14.7% (9.0%-20.1%), chronic lung disease 11.9% (5.1%-18.2%), immunocompromised 15.0% (7.2%-22.2%), chronic kidney disease 8.4% (0.5%-15.7%). Overall, among adults with underlying medical conditions, mRNA-1273.222 was more effective than BNT162b2 Bivalent, especially in preventing COVID-19-related hospitalizations.