Safety Monitoring of Bivalent COVID ‐19 mRNA Vaccines Among Recipients 6 Months and Older in the United States

PURPOSE: Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes post-licensure. We evaluated health outcomes following bivalent COVID-19 Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273.222) vaccination in the United States. METHODS: Multiple health outcomes were monitored monthly from August 2022 to July 2023 in four administrative claims databases (CVS Health, Carelon Research, Optum, and Medicare). The study included individuals 6 months and older who received a bivalent COVID-19 BNT162b2 or mRNA-1273.222 vaccination during the study period and met a minimum continuous enrollment requirement in a medical insurance plan prior to COVID-19 vaccination. Descriptive analyses monitored counts of vaccinations, outcomes, and concomitant COVID-19 and influenza vaccination. Maximized Sequential Probability Ratio Testing (MaxSPRT) tested for elevations in the observed incidence rate of outcomes post-vaccination compared to annual historical rates estimated from 2019 or 2020, adjusted for claims delay in the observed rate. Where case counts permitted, historical rates were standardized by age and/or sex for all persons, and race and/or nursing home residency status for Medicare persons only. RESULTS: Overall, 13.9 million individuals 6 months and older received a bivalent COVID-19 vaccine. A statistical signal occurred for two outcomes in one database (significance level of 1%): anaphylaxis following both bivalent COVID-19 vaccines in persons 18-64 years and myocarditis/pericarditis following bivalent BNT162b2 vaccines in individuals 18-35 years. Among 642 142 vaccinated children 6 months-17 years, no signals were identified. CONCLUSIONS: Results were consistent with published COVID-19 vaccine safety studies and support the safety profile of bivalent COVID-19 mRNA vaccines.