Association of new onset seizure and COVID-19 vaccines and long-term follow-up: A systematic review and meta-analysis

Objective: Seizures have been reported as an adverse event of the COVID-19 vaccine. However, there is no solid evidence of increased seizure occurrence compared to the general population. This study was undertaken to investigate seizure occurrence among COVID-19 vaccine recipients compared to unvaccinated controls. Methods: A systematic search was made of PubMed, Web of Science, Scopus, and Cochrane Library up to April 9, 2024. Studies reporting seizure occurrence following COVID-19 vaccination were included. This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework and was conducted using random- and common-effect models. The risk of bias in the studies was evaluated by the Newcastle-Ottawa Scale. The outcome of interest was new onset seizure incidence proportion compared among (1) COVID-19 vaccine recipients, (2) unvaccinated cohorts, and (3) various types of COVID-19 vaccines. Results: Forty studies were included, of which seven entered the meta-analysis. Results of the pooled analysis of the new onset seizure incidence (21- or 28-day period after vaccination) in 13 016 024 vaccine recipients and 13 013 262 unvaccinated individuals by pooling the cohort studies did not show any statistically significant difference between the two groups (odds ratio [OR] = .48, 95% confidence interval [CI] = .19-1.20, p = .12, I-2 = 95%, tau(2) = .7145). Pooling four studies accounting for 19 769 004 mRNA versus 47 494 631 viral vector vaccine doses demonstrated no significant difference in terms of new onset seizure incidence between the groups (OR = 1.18, 95% CI = .78-1.78, p = .44, I-2 = 0%, tau(2) = .004). Significance: This systematic review and meta-analysis shows no statistically significant difference in the risk of new onset seizure incidence between COVID-19 vaccinated individuals and unvaccinated individuals.