COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS). An association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service (NHS) data in England and a multicentre surveillance study from UK hospitals, to investigate the relationship between COVID-19 vaccination and GBS. Firstly, we present a retrospective analysis of every GBS patient in England in the National Immunoglobulin Database (NID) linked with their COVID-19 vaccination data. Cases of GBS identified in the National Immunoglobulin Database (NID) from 8 December 2021 to 8 July 2021 were linked to data from the National Immunisation Management System (NIMS) in England to identify exposure to a COVID-19 vaccine. For the NID/NIMS linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database, regardless of vaccine exposure, with vaccine timings and GBS phenotypic data. For this multicentre UK surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS. 996 GBS cases were recorded in the NID from January to October 2021. A spike of GBS cases above the 2016-2020 average occurred in March-April 2021. In England, among all cases of GBS, 198 occurred within 6 weeks of the first-dose COVID-19 vaccination (0.618 cases per 100,000 vaccinations, 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer), 1 mRNA-1273 (Moderna)). The excess of GBS occurs with a peak at 24 days; first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases was between 98-140 cases for first-dose ChAdOx1 nCoV-19 vaccination from January-July 2021. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. 121 patients were reported in the separate multicentre surveillance dataset with no phenotypic or demographic differences identified between vaccinated and non-vaccinated GBS cases. Data from the linked NID/NIMS dataset suggest that first-dose ChAdOx1 nCoV-19vaccination is associated with an excess GBS risk of 0.576 (95%CI 0.481-0.691) cases per 100,000 doses. However, further data reported from a multicentre surveillance dataset suggest that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19specific first dose link warrants further study.