Association of Seizure with COVID-19 Vaccines in Persons with Epilepsy: A Systematic Review and Meta-analysis

Objective: Seizure following immunization, especially in persons with epilepsy (PwE), has long been a concern, and seizure aggravation followed by Coronavirus Disease 2019 (COVID-19) vaccines is a serious issue for PwE. The immunization rate in PwE has been lower compared to same-age controls due to vaccine hesitancy and concerns about seizure control. Herein, we systematically reviewed the seizure activity-related events in PwE following COVID-19 vaccination. Methods: Four search engines were searched from inception until January 31, 2023, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. Random- and fixed-effect models using the logit transformation method were used for meta-analysis. The quality of the studies was evaluated by the Newcastle-Ottawa scale. Outcomes of interest included (a) pooled proportion of increased seizure frequency and (b) pooled incidence proportion of status epilepticus (SE) in PwE receiving COVID-19 vaccines. Results: Of the 2207 studies identified, 18 met eligibility criteria, of which 16 entered the meta-analysis. The pooled proportion of increased seizure frequency (16 studies-4197 PwE) was 5% (95CI: 3%-6%, I2 =57%), further subcategorized into viral vector (3%, 95CI: 2%-7%, I2 =0%), mRNA (5%, 95CI: 4%-7%, I2 =48%), and inactivated (4%, 95CI: 2%-8%, I2 =77%) vaccines. The pooled incidence proportion of SE (15 studies-2480 PwE) was 0.08% (95CI: 0.02%-0.32%, I2 =0%), further subcategorized into the viral vector (0.00%, 95CI: 0.00%-1.00%, I2 =0%), mRNA (0.09%, 95CI: 0.01%-0.62%, I2 =0%), and inactivated (0.00%, 95CI: 0.00%-1.00%, I2 =0%) vaccines. No significant difference was observed between mRNA and viral vector vaccines (5 studies, 1122 vs. 198 PwE, respectively) regarding increased seizure frequency (OR: 1.10, 95CI: 0.49-2.50, p-value=0.81, I2 =0%). Significance: The meta-analysis proposed a 5% increased seizure frequency following COVID-19 vaccination in PwE, with no difference between mRNA and viral vector vaccines. Furthermore, we found a 0.08% incidence proportion for SE. While this safety evidence is noteworthy, this cost should be weighed against vaccination benefits. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This meta-analysis used data from previously published studies. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript