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

Abstract

Abstract Background The emergence of Omicron variants coincided with declining vaccine-induced protection against SARS-CoV-2 infection and other COVID-19-related outcomes. Two bivalent mRNA vaccines, mRNA-1273.222 (Moderna) and BNT162b2 Bivalent (Pfizer-BioNTech) were developed to provide greater protection against the predominate circulating variants by including the mRNA that encodes both the ancestral (original) strain and BA.4/BA.5. We estimated their relative vaccine effectiveness (rVE) in preventing COVID-19-related outcomes in the US. Methods We conducted a retrospective cohort study using a US nationwide dataset linking primary care electronic health records (EHR) and pharmacy/medical claims data. The adult study population (aged ≥18 years) received either mRNA-1273.222 or BNT162b2 Bivalent vaccination between August 31, 2022, and February 28, 2023. We used a propensity score weighting based on the inverse probability of treatment to adjust for the baseline differences in age, sex, race, ethnicity, geographic region, vaccination week, and health status between groups. Outcomes evaluated were rVE of the two bivalent mRNA vaccines against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary). We weighted the vaccine groups prior to analysis and estimated adjusted hazard ratios (HR) using multivariable Cox regression models. We calculated rVE as (1−HR) × 100. Results We evaluated outcomes for 1,034,538 mRNA-1273.222 and 1,670,666 BNT162b2 Bivalent vaccine recipients. The adjusted rVE of mRNA-1273.222 versus BNT162b2 Bivalent vaccines against COVID-19-related hospitalization was 9.8% (95% confidence interval: 2.6%–16.4%). The adjusted rVE against COVID-19-related outpatient visits was 5.1% (95% CI: 3.2%–6.9%). When evaluated by age group, the incremental relative effectiveness was greater. Among adults ≥ 65, rVE against COVID-19-related hospitalizations and outpatient visits was 13.5% (95% CI: 5.5%–20.8%) and 10.7% (8.2%–13.1%), respectively. Conclusion We found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and outpatient visits, with increased benefits in older adults.