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Background and Objectives: Existing data regarding occurrence of Guillain-Barré syndrome (GBS) following COVID-19 infection and vaccination are inconclusive. We aimed to assess the association between GBS and both SARS-CoV-2 infection and COVID-19 vaccine.

Methods: We conducted a nested-case control study in a cohort of 3,193,951 patients aged≥16 years, without a diagnosis of prior GBS, from the largest healthcare provider in Israel. Subjects were followed from January 1st, 2021, until June 30th, 2022, for the occurrence of GBS. Ten randomly selected controls were matched to each case of GBS on age and sex. We assessed both SARS-CoV-2 infection and COVID-19 vaccine administration in the prior 6 weeks in cases and controls.

Results: Overall, 76 patients were diagnosed with GBS during follow-up and were matched to 760 controls. A positive test for SARS-CoV-2 was detected in 9 (11.8%) cases, and 18 (2.4%) controls. An administration of COVID-19 vaccine was detected in 8 (10.5%) cases (all Pfizer-BioNTech [BNT162b2] vaccine), and 136 (17.9%) controls (134 Pfizer-BioNTech vaccine). Multivariable conditional logistic regression models showed that the OR for GBS associated with SARS-CoV-2 infection and COVID-19 vaccine administration was 6.30 (95% CI 2.55-15.56) and 0.41 (95% CI 0.17-0.96), respectively. The results were similar when exposure to SARS-CoV-2 infection or COVID-19 vaccine administration were ascertained in the prior 4 and 8 weeks, although did not reach statistical significance for COVID-19 vaccine at 4 weeks.

Conclusions: Our study suggests that SARS-CoV-2 infection is associated with increased risk of GBS, while Pfizer-BioNTech COVID-19 vaccine is associated with decreased risk of GBS.