No significant increase in Guillain-Barré syndrome after COVID-19 vaccination in adults: A vaccine adverse event reporting system study

OBJECTIVE: To investigate the association between Guillain-Barré syndrome (GBS) and COVID-19 vaccination. BACKGROUND: On July 13, 2021, the US Food and Drug Administration (FDA) released a new warning that Johnson & Johnson COVID-19 vaccine could increase the risk of developing GBS. METHODS: The reporting rate of adult GBS after COVID-19 vaccination, ascertained with Brighton criteria, was compared with the reporting rate after other vaccinations during the same time period, and also compared with the reporting rate during control periods. Statistical methods such as proportion tests, and Pearson’s chi-squared test were utilized to identify significant relationships. Self-controlled and case centered analyses were conducted. A machine learning model was utilized to identify the factors associated with a worse outcome defined as emergency room (ER) or doctor visits, hospitalizations, and deaths. RESULTS: The reporting rate of GBS after COVID-19 vaccination was significantly higher than after influenza and other vaccinations (49.7, 0.19, 0.16 per 10 million, p < 0.0001). However, the reporting rate was within the incidence range of GBS in the general population. Using self-controlled and case centered analyses, there was a significant difference in the reporting rate of GBS after COVID-19 vaccination between the risk period and control period (p < 0.0001). There was an estimated 0.7–1.7 per million excess reports of GBS within 6 weeks of COVID-19 vaccination. Machine learning model demonstrated that female gender and age between 18 and 44 are associated with worse outcome. No association was found between the onset interval of GBS and its prognosis. CONCLUSIONS: Although the reporting rate of GBS after COVID-19 vaccination was not statistically different than that of the general population, the increased reporting of GBS within the first 6 weeks after COVID-19 vaccination, more so than with other vaccinations, suggests that some cases of GBS are temporally associated with COVID-19 vaccination. However, there is a reduction in the reporting rate of GBS after other vaccines, compared to reporting rates pre-COVID-19, highlighting limitations inherent in any passive surveillance system. These findings warrant continuous analysis of GBS after COVID-19 vaccination. Further improvement of the machine learning model is needed for clinical use.