Multiregional Population-Based Cohort Study for Evaluation of the Association Between Herpes Zoster and mRNA Vaccinations for Severe Acute Respiratory Syndrome Coronavirus-2: The VENUS Study

BACKGROUND: This study was performed to assess the increased risk of herpes zoster (HZ) associated with mRNA vaccines for coronavirus disease 2019. METHODS: This population-based cohort study was conducted in 4 municipalities in Japan. Individuals covered under public health insurance systems without a history of HZ were followed from October 1, 2020 to November 30, 2021. Incidence rates of HZ within 28 days of BNT162b2 or mRNA-1273 vaccination were compared. Adjusted incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using a Poisson regression model, including vaccination status as a time-dependent covariate. Subgroup analyses by sex, age, and municipality were also conducted. RESULTS: A total of 339 548 individuals (median age, 74 years) were identified. During follow up, 296 242 individuals (87.2%) completed the primary series, among whom 289 213 and 7019 individuals received homologous BNT162b2 and mRNA-1273 vaccines, respectively. The adjusted IRRs of the first and second BNT162b2 vaccinations were 1.05 (95% CI, 0.84–1.32) and 1.09 (95% CI, 0.90–1.32), respectively. No cases of HZ were observed after mRNA-1273 vaccination. In subgroup analysis, the adjusted IRR of the second BNT162b2 vaccination was 2.94 (95% CI, 1.41–6.13) in individuals aged <50 years old. CONCLUSIONS: No increased risk of HZ was found after BNT162b2 vaccination in the overall study population. However, an increased risk was observed in the younger subgroup.