(358) Safety Monitoring of Bivalent COVID-19 mRNA Vaccines Among Recipients 6 months and Older in the United States

Background: Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials.

Objectives: To evaluate health outcomes following bivalent COVID-19 Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273.222) vaccination among individuals 6 months and older in the United States.

Methods: This near real-time surveillance study conducted monthly monitoring of pre-specified health outcomes following receipt of bivalent COVID-19 Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273.222) vaccines from August 2022 – July 2023 using administrative commercial health claims data (Carelon Research, CVS Health, and Optum) for persons aged 6 months – 64 years old and Medicare Fee-For-Service claims data for persons aged 65 years and older. The study included persons who received a bivalent COVID-19 BNT162b2 or mRNA-1273.222 vaccine during the study period with continuous enrollment in a medical insurance plan from the start of an outcome-specific clean interval to their COVID-19 vaccination date. Immunization Information Systems (IIS) data were used to improve vaccination capture.
Twenty outcomes were monitored in BNT162b2 vaccine recipients 6 months-4 years, and mRNA-1273.222 vaccine recipients 6 months-5 years. Twenty-one outcomes were monitored in BNT162b2 vaccine recipients 5-17 years and mRNA-1273.222 vaccine recipients 6-17 years. Eighteen outcomes were monitored in persons 18 years and older for both mRNA vaccines. Descriptive analyses monitored vaccine uptake, outcome counts and concomitant COVID-19 and influenza vaccination. Sequential analyses tested for elevated risk of each outcome in a pre-specified post-vaccination risk interval, or a period of hypothesized elevation based on clinical guidance, compared to a historical baseline (2019 or 2020).

Results: Overall, 13.9 million individuals 6 months and older received a single bivalent COVID-19 mRNA vaccine. The statistical threshold for a signal was met for two outcomes in the Carelon database only: anaphylaxis following bivalent BNT162b2 (n < 11 cases) and mRNA-1273.222 (n < 11 cases) vaccines in persons 18-64 years, and myocarditis/pericarditis following bivalent BNT162b2 vaccines in persons 18-35 years (n < 11 cases). No signals were identified in those 6 months – 17 years or in adults aged 65 years and older.

Conclusions: Statistical thresholds for a signal were met for anaphylaxis and myocarditis/pericarditis, consistent with results from prior COVID-19 vaccine safety studies published. This study contributes to regulatory decision-making for COVID-19 vaccines and public health and supports the conclusion that the benefits of vaccination outweigh the risks.