Covid-19 vaccines and Guillain-Barré syndrome: A perspective from spontaneous report data

ABSTRACT

Introduction: The causal relationship between Guillain-Barré syndrome (GBS) and vaccination is still disputed. Our aim was to assess the association between GBS and mRNA (Tozinameran and Elosameran) or adenovirus-vectored (ChAdOx1 nCoV-19 and Ad26.CoV2.S) vaccines. Material and methods: Spontaneous reports of GBS following mRNA-based or adenovirus-vectored vaccination were extracted from Vigibase®. For countries with both available exposure data obtained from Our World in Data website and national incidence of GBS, estimation of the reporting rates and an observed-to-expected (OE) analysis based on the background incidence using a 21-and 42-day risk window were performed. Results: A total of 2,499 cases were included with adenovirus-vectored vaccines in 1,157 (46.3%) and mRNA-based vaccines in 1,342 (53.7%). Sex ratio was 1.09 and median age 57 years (IQR 45-66). The reporting rates per 100,000 person-years within the 42-day window were 5.57 (95% CI, 5.13-6.03) for adenovirus-vectored vaccines and 1.39 (95% CI, 1.31-1.47) for mRNA vaccines compared to a background incidence of 1.2 to 3.1 per 100,000 person-years. For mRNA-based vaccines, the OE was lower than 1 for both risk windows in all European countries and slightly elevated only for the 21-day risk window in the US. For adenovirus-vectored vaccines, the OE ratio was consistently above 2.0 across countries and for both risk windows. Sensitivity analyses using scenarios based on an under-reporting rate of 50% and estimates of confirmed cases of GBS ranging from 55% to 76%, minimally altered these results. Discussion/Conclusion: These findings both suggested the absence of safety concern for GBS with mRNA vaccines and a small increased risk with adenovirus-vectored vaccine. Despite some evidence of differential reporting between countries, our study based on a high number of cases of GBS together with exposure data offered unique opportunities to address the relevance of spontaneous reporting of rare events for epidemiological purposes.