(356) Risk of Encephalitis and Meningitis After COVID-19 Vaccination in South Korea: a Self-controlled Case Series Analysis

Background: Several neurological manifestations shortly after a receipt of coronavirus infectious disease 2019 (COVID-19) vaccine have been described in the recent case reports. Among those, there had been relatively few observational studies on encephalitis or meningitis after COVID-19 vaccination, partly owing to very few cases recorded in the data.

Objectives: To evaluate the risk of encephalitis and meningitis after COVID-19 vaccination in the entire South Korean population

Methods: We conducted self-controlled case series (SCCS) analysis using the COVID-19 immunization record data from Korea Disease Control Agency between February 2021 and March 2022, linked with the National Health Insurance Database between January 2021 and October 2022. We retrieved all medical claims of adults aged 18 years or older who received at least one dose of COVID-19 vaccines (BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S), and included only those who had a diagnosis record for encephalitis or meningitis within the 240-day post-vaccination period. With Day 0 defined as the date of vaccination, risk window was defined as Days 1 -28 and control window as the remainder period excluding the risk windows within the 240-day period. We used conditional Poisson regression to estimate the incidence rate ratios (IRR) with 95% confidence intervals (CI), stratified by dose and vaccine type.

Results: From 129,956,027 COVID-19 vaccine doses administered to 44,564,345 individuals, there were 251 and 398 cases of encephalitis and meningitis during the risk window, corresponding to 1.9 and 3.1 cases per 1 million doses, respectively. Overall, there was an increased risk of encephalitis in the first 28 days of COVID-19 vaccination (IRR 1.26; 95% CI 1.08-1.47), which was only significant after a receipt of ChAdOx1-S (1.49; 1.03-2.15). For meningitis, no increased risk was observed after any dose of COVID-19 vaccine (1.03; 0.91-1.16).

Conclusions: Our finding complements the existing data to support the temporal association between encephalitis and COVID-19 vaccination. However, it is important to note that the absolute risk was small and should not impede COVID-19 vaccine confidence. Rather, the finding is to inform clinical practice to enable prompt diagnosis and treatment for patients presenting with neurological signs after COVID-19 vaccination. Moreover, while it was reassuring to note no increased risk of meningitis after COVID-19 vaccination, further studies are needed to confirm this finding as both encephalitis and meningitis share similar etiology.