loading . . . Safety Monitoring of Multiple Health Outcomes Following 2023–2024 COVID-19 Vaccination among Medicare Beneficiaries Aged 65 Years and Older in the United States Background COVID-19 vaccines are well-established as safe. However, continued surveillance of COVID-19 vaccines is important to ensure the safety of newly formulated vaccines. This study evaluated the association between vaccination with 2023-2024 formula COVID-19 vaccines and multiple health outcomes among Medicare beneficiaries aged 65 years and older in the United States. Methods The study used health plan data from the Medicare Fee-for-Service (FFS) claims database and extended from September 2023 to April 2024. We monitored the uptake of 2023–2024 COVID-19 vaccines (Pfizer-BioNTech, Moderna, Novavax), and where case counts were available, we used a self-controlled case series design to assess the association between vaccination and prespecified health outcomes. We used conditional Poisson regression to estimate incidence rate ratios (IRRs), attributable risks (ARs) and corresponding 99% confidence intervals (CIs). Analyses were adjusted for outcome seasonality, event-dependent observation time for outcomes with high case fatality rates, and outcome misclassification where feasible. Results Approximately 7.6 million Medicare FFS beneficiaries received a 2023–2024 COVID-19 vaccination. There was an even distribution of people who received Pfizer-BioNTech (3,689,356; 48.80%) or Moderna (3,841,245; 50.80%) vaccinations and very few who received Novavax (30,171; 0.40%). There was a statistically significant elevation in anaphylaxis risk associated with 2023–2024 Pfizer-BioNTech vaccines in the seasonality-adjusted analysis (IRR: [99% CI: 1.07, 15.30]) that was no longer statistically significant after accounting for potential outcome misclassification (IRR: 3.90 [99% CI: 0.49, 30.90]). Anaphylaxis cases attributable to 2023–2024 Pfizer-BioNTech vaccination were rare (AR per 100,000 doses: 0.09 [99% CI: −0.08, 0.25]). No other statistically significant elevations in risk were observed. Conclusion There were no new safety signals identified following 2023–2024 COVID-19 vaccinations among U.S. Medicare beneficiaries aged 65 years and older. A potential, but rare, elevation in anaphylaxis incidence rates following 2023–2024 Pfizer-BioNTech COVID-19 vaccination was observed. HIGHLIGHTS ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols [https://bestinitiative.org/wp-content/uploads/2024/01/BEST\\_COVID19\\_Safety\\_Protocol\\_2023-2024.pdf][1] ### Funding Statement This work was funded by the U.S. Food and Drug Administration through the Department of Health and Human Services (HHS) Contracts [HHSF-223-2018-10020I and GS-10F-0133S], Task Orders [75F40123F19005 and 75FCMC21F0067]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was part of public health surveillance, and therefore, it was exempted from institutional review board approval and informed consent under the Common Rule. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: https://bestinitiative.org/wp-content/uploads/2024/01/BEST_COVID19_Safety_Protocol_2023-2024.pdf https://www.medrxiv.org/content/10.1101/2025.01.03.25319975v1.full
