Three vaccines against COVID-19 are currently available for use in children in the US, including the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) COVID-19 messenger RNA (mRNA) vaccines for those aged 6 months to 17 years and the protein-based NVX-CoV2373 (Novavax) vaccine for those aged 12 to 17 years.^1-3 As of May 2023, the Centers for Disease Control and Prevention (CDC) reported that 31.78 million children had received at least 1 COVID-19 vaccine dose and 26.2 million children had completed the primary series of approximately 73 million children aged 6 months to 17 years in the US.⁴ The US Food and Drug Administration (FDA), utilizing the Biologics Effectiveness and Safety (BEST) Initiative, has been monitoring the safety of COVID-19 vaccines in children since their authorization by applying a near-real-time monitoring framework to evaluate the safety of COVID-19 vaccines. The near-real-time surveillance process is a signal detection or screening method and the first step in safety monitoring of these vaccines. This framework is designed to be sensitive enough to rapidly detect less common safety concerns as data accrue. However, results of such a study design do not establish a causal relationship between the vaccines and health outcomes and need to be interpreted with caution because of the limited adjustment for confounding and other forms of bias.

Importance: The United States Food and Drug Administration conducts routine post-market surveillance of approved vaccines to identify and characterize health outcomes risk associated with vaccination. Pre-licensure clinical trials of RSVPreF3+AS01 and RSVPreF vaccines identified a small number of Guillain-Barré syndrome cases, a serious acute demyelinating disease, following vaccination. Objective: To use Centers for Medicare & Medicaid Services Medicare Fee-for-Service administrative claims and Medicare Part D data to evaluate risk of Guillain-Barré syndrome following respiratory syncytial virus vaccination. Design, Settings, and Participants: We studied vaccines administered between May 3, 2023, when vaccines were first approved, through January 28, 2024. This self-controlled case series study design compared the incidence of Guillain-Barré syndrome during risk intervals of 1–42 days following vaccination to the incidence in subsequent control intervals (43–90 days) among Medicare beneficiaries, aged 65 years and older, enrolled in Fee-for-Service and Medicare Part D. Exposures: Receipt of a single dose of RSVPreF3+AS01 or RSVPreF vaccines. Outcomes: Guillain-Barré syndrome was identified using diagnosis code G61.0 in the primary diagnosis position on hospital inpatient claims; returned cases were confirmed via medical record review using Brighton Collaboration’s case definition. Results: We captured approximately 3.23 million Medicare beneficiaries that received respiratory syncytial virus vaccination during the study period. A total of 95 incident Guillain-Barré syndrome cases were observed following respiratory syncytial virus vaccination. In our chart-confirmed self-controlled case series analysis, we observed an increased incidence of Guillain-Barré syndrome following RSVPreF3+AS01 (IRR: 2.46, [95% CI: 1.19, 5.08]) with an attributable risk of 6.5 cases per 1 million doses. We observed an increased, yet not statistically significant, incidence of Guillain-Barré syndrome following RSVPreF (IRR: 2.02, [95% CI: 0.93, 4.40]) with an attributable risk of 9 cases per 1 million doses. Conclusion and Relevance: Findings from this self-controlled case series study suggest an increased risk of Guillain-Barré syndrome during 1-42 days following respiratory syncytial virus vaccination, with fewer than 10 excess Guillain-Barré syndrome cases per 1 million vaccine doses among Medicare beneficiaries 65 years and older. The U.S. Food and Drug Administration maintains that the substantial benefits of RSV vaccination outweigh these identified risks associated with vaccines. Key Points: Question: Is there an increased risk of developing Guillain-Barré syndrome (GBS) following vaccination with RSVPreF3+AS01 (AREXVY®) and RSVPreF (ABRYSVO®) among Medicare beneficiaries aged 65 years and older? Findings: In a self-controlled case series analysis of Medicare beneficiaries with medical record review, we estimated the incidence rate ratio (IRR) comparing GBS in pre-specified risk and control intervals following vaccination with RSVPreF3+AS01 (IRR: 2.46, 95%CI: 1.19-5.08) or RSVPreF (IRR: 2.02, 95%CI: 0.93-4.40). RSV vaccines were associated with fewer than 10 excess GBS cases per 1 million vaccine doses. Meaning: These findings suggest an increased risk of GBS following RSV vaccination.