COVID-19 mRNA Vaccination Reduces Guillain-Barre Syndrome Risk: Evidence from a Large Longitudinal Cohort Study

Abstract The association between COVID-19 vaccination and Guillain-Barre syndrome (GBS) has been previously investigated with inconsistent results, largely due to limited data and lack of concurrent controls. To address this problem, a large longitudinal cohort study was conducted using National COVID Cohort Collaborative (N3C) data. While COVID-19 infection was associated with increased GBS occurrence, COVID-19 vaccination was associated with significantly reduced GBS risk relative to unexposed (unvaccinated and uninfected) control, corresponding to a 61% lower 30-day risk (incidence risk ratio: IRR = 0.39, P < 0.01), consistent with multivariable Cox regression showing a similar reduction (adjusted hazard ratio: aHR = 0.41, P < 0.01). This protective association was observed only among recipients of mRNA vaccines (BNT162b2: IRR = 0.38, P < 0.01; mRNA-1273: IRR = 0.24, P < 0.01), but not among recipients of adenoviral-vector vaccines (IRR = 1.38, P > 0.05). Prior COVID-19 vaccination also reduced infection-associated GBS risk. Additional factors associated with GBS risk included sex, vaccine dose, and pre-existing comorbidities such as stroke, neurological disorders, and autoimmune diseases. Overall, our N3C large-scale study provides evidence that COVID-19 mRNA vaccination reduces GBS risk, supporting the safety profile of mRNA vaccines and warranting further mechanistic investigation.