(A-331) Safety Monitoring of Multiple Health Outcomes following 2023–2024 COVID-19 Vaccination among Commercial Health Plan Enrollees Aged 6 Months–64 Years in the United States

Background: While COVID-19 vaccines are well-established as safe, postmarketing surveillance of these vaccines is important to monitor the safety of new vaccine formulations given their widespread use, including in vulnerable populations.

Objectives: To assess the association between 2023–2024 formula COVID-19 vaccination and 17 health outcomes among persons aged 6 months–64 years in the United States (U.S.).

Methods: The study used longitudinal health data from three large commercial health databases in the U.S. (Carelon Research, CVS Health, and Optum) from September 11, 2023 through database-specific end dates ranging from March 1 to June 15, 2024. Where feasible, claims data was linked to state-based immunization information system data to supplement vaccine capture. We monitored the uptake of 2023–2024 COVID-19 vaccines (Pfizer-BioNTech, Moderna, Novavax) among individuals aged 6 months–64 years. Where case counts permitted, we used a self-controlled case series design to assess the association between vaccination and 17 predefined health outcomes (cardiovascular and vascular, hematological, neurologic, and other outcomes), comparing the incidence of outcomes during periods of risk immediately following vaccination to later control periods. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 99% confidence intervals (CIs) adjusted for outcome seasonality. Analyses were run in individual databases for each outcome by vaccine brand in prespecified age groups, and pooled using meta-analyses where feasible.

Results: Among 4,236,138 million vaccine recipients, 2,297,024 received Pfizer-BioNTech (54.22%), 1,909,876 received Moderna (45.09%), and 29,238 received Novavax (0.69%). Of these, 4,151,149 (97.99%) individuals received a single dose. We identified a statistically significant elevated risk of febrile seizure in days 0–1 following Moderna vaccination ( < 11 cases) among children aged 6 months–5 years (meta-analyzed IRR: 3.60 [99% CI: 1.32, 9.77]), concentrated among children 2–5 years (meta-analyzed IRR: 6.98 [99% CI: 1.61, 30.29]). Myocarditis/pericarditis cases were rare; however, in one database, an imprecise elevation in risk ( < 11 cases) was observed following Pfizer-BioNTech among children 6 months–17 years (IRR: 23.71 [99% CI: 1.01, 556.02]), which was no longer statistically significant after seasonality adjustment (IRR 23.06 [99% CI]: 0.98, 540.74]). No other evidence of a statistically significant elevation in risk was found.

Conclusions: We found evidence for an elevated risk of previously documented rare adverse events following COVID-19 vaccination. No new safety concerns were found following 2023–2024 COVID-19 vaccination among U.S. health plan enrollees aged 6 months–64 years.