Abstract

The purpose of this study was to determine the risk of herpesviral keratitis associated with 4 coronavirus disease 2019 (COVID-19) vaccines approved in South Korea, using large-scale data from the National Health Insurance Service. The study included 8,528,254 individuals, with cohorts categorized based on COVID-19 vaccination status. Two investigations were conducted: The first aimed to assess the risk of new-onset herpesviral keratitis while the second study focused on the risk of relapse in individuals with a preexisting diagnosis. Propensity score matching was used for cohort balancing, and various covariates, including vaccine types and comorbidities, were considered. Statistical analyses, including Cox proportional hazard regression, were used to calculate adjusted hazard ratio (aHR) and assess the risk of herpesviral keratitis. Individuals receiving COVID-19 vaccination exhibited a higher risk of new-onset herpesviral keratitis compared with the unvaccinated control group (aHR 1.43, 95% confidence interval, 1.19-1.73). Both mRNA and non-mRNA vaccines demonstrated an increased risk. Individuals with preexisting herpetic keratitis who received COVID-19 vaccination showed a higher risk of relapse herpesviral keratitis compared with the unvaccinated control group (aHR 1.98, 95% CI, 1.29-3.03). Sensitivity analyses supported the robustness of the results. This analysis of a large national health insurance database suggests an increased risk of both new-onset and relapse of herpesviral keratitis associated with COVID-19 vaccination in South Korea. While COVID-19 vaccination is crucial for pandemic control, health care providers should be aware of potential herpesvirus reactivation and consider appropriate prophylaxis and treatment for at-risk individuals.

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