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Research Article: Temporal and disproportionality analysis of vaccine-associated Guillain-Barré syndrome: a 21-year VAERS study

Date Published: 2026-08-04

Abstract:
Guillain-Barré syndrome (GBS) remains a critical vaccine safety concern. We conducted a comprehensive pharmacovigilance analysis of 21-year VAERS data to identify vaccine-GBS disproportionality signals and temporal patterns. We analyzed 9,755,435 VAERS reports (2004–2024) including 2,216 GBS cases using four disproportionality algorithms (ROR, PRR, IC, EBGM). Time-to-onset was compared between 1,534 GBS and 120,763 non-GBS events using Kaplan–Meier analysis. Twenty-six vaccines met all four algorithm criteria, predominantly influenza formulations (19/26; RORs 2.4–8.5), validating historical surveillance observations. Novel signals emerged for both RSV vaccines (Arexvy ROR 3.01, Abrysvo ROR 6.82) and zoster vaccine (ROR 3.01), consistent with post-marketing estimates of 3–9 excess cases per million doses. COVID-19 vaccines showed no concordant signals despite established Janssen associations, reflecting denominator dilution from 7.89 million COVID-19 reports (81% of the database). GBS exhibited characteristic delayed onset—median 13?days (IQR 5–29) versus 0?days for non-GBS events ( p <?0.001)—with 44.8% of cases occurring 8–30?days post-vaccination, the biologically plausible window for vaccine-triggered autoimmunity. Demographically, GBS reports showed male predominance (OR 2.4) and were overwhelmingly classified as serious outcomes compared with non-GBS reports (76.1% vs. 9.6%, p <?0.001); serious outcomes included death, life-threatening events, hospitalization (new or prolonged), or permanent disability. Multiple vaccines showed disproportionate GBS reporting signals with delayed temporal patterns consistent with biological plausibility; because these derive from passive surveillance, they are hypothesis-generating and do not establish causality. Despite rare associations, absolute risks (1–9 per million doses) are far outweighed by disease prevention benefits, supporting current vaccination policies with ongoing surveillance.

Introduction:
Guillain-Barré syndrome (GBS) remains a critical vaccine safety concern. We conducted a comprehensive pharmacovigilance analysis of 21-year VAERS data to identify vaccine-GBS disproportionality signals and temporal patterns.

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