(BSPOT50) Risk of New-Onset Seizures Following Immunization against COVID-19 in South Korea: A Self-Controlled Case-Series Study

Background: While the significance of COVID-19 vaccines is highly regarded in preventing infections and their post-acute sequelae, cases of new-onset seizures (NOS) following vaccination have continuously been reported across various ethnicities, ages, and vaccine types. However, there is a paucity of safety evidence regarding the risk of NOS following COVID-19 vaccination.

Objectives: To investigate the potential association between NOS and COVID-19 vaccination among entire vaccine recipients in South Korea using a large-linked database including a variety of COVID-19 vaccine types.

Methods: We conducted a self-controlled case series study using a nationwide database of Korea by linking the COVID-19 vaccination registry (2021.02-2022.10) and healthcare claims data from the National Health Insurance Service (2002.01-2022.10). We identified patients aged ≥ 18 years who received their first dose of COVID-19 vaccination (BNT162b2, ChAdOx1 nCoV-19, mRNA-1273, NVX-CoV2373, and Ad26.COV2.S) and had a NOS diagnosis with prescription of anti-seizure medications during the study period. Observation period was defined as 240 days following the vaccination. The risk of NOS was evaluated within the risk window of 28 days following the vaccination compared to control window (the rest observation period excluding risk window). Incidence rate ratios (IRR) with 95% confidence intervals (CI) were estimated using conditional Poisson regression model. Subgroup analyses across vaccine types, doses, and underlying conditions and sensitivity analyses by varying the risk period and outcome definition were conducted.

Results: A total of 129,956,027 doses of COVID-19 vaccine were administered in Korea during the study period. Among 42,155,198 adults who received COVID-19 vaccine, we identified 1,849 patients with NOS in the risk window. There was no increased risk of NOS within the 28-days period after the vaccination (IRR 0.99, 95% CI 0.94-1.05). While the results from subgroup analyses for vaccine type were largely consistent with our main findings (0.95, 0.88-1.03 for BNT162b2; 0.95, 0.77-1.16 for ChAdOx1 nCoV-19; 1.58; 0.52-4.83 for Ad26.COV2.S), marginally elevated risk was observed for mRNA-1273 (1.21, 1.04-1.42). Subgroup analyses across underlying comorbidities and sensitivity analyses yielded consistent results with the primary findings.

Conclusions: In this nationwide study, there was no evidence of an increased risk of NOS following COVID-19 vaccination. These findings can be utilized as comprehensive safety evidence for clinical decision-making and contribute to public confidence in vaccination campaigns. Further research regarding the differences in risk across vaccine types is warranted, given a marginal increase in risk observed for mRNA-1273.