Association Between Acute Vulvar Ulcers and Gene-Based COVID-19 Vaccines

OBJECTIVE: Acute vulvar ulcers have been reported following gene-based COVID-19 vaccinations, though causality remains uncertain. This study aims to examine the association between vaccination and ulcer occurrence. MATERIALS AND METHODS: This observational study analyzed vulvar ulcer cases reported to the Vaccine Adverse Event Reporting System (VAERS) from January 2002 to February 2022. Risk was estimated by comparing VAERS-reported ulcer cases with vaccine recipient data from the COVID Data Tracker. Causality was assessed using the Bradford Hill criteria. RESULTS: From 2021 to 2022, the proportion of vulvar ulcers among reported adverse events exceeded the upper control limits for the first time since 2002. Most cases (134/137, 97.8%) were linked to COVID-19 vaccines. Ad26.COV2.S had the highest relative risk (2.72 vs. BNT162b2; 95% CI: 1.17-6.30). For two-dose vaccines, the second dose posed a higher risk (dose 2 vs. dose 1: RR 3.52; 95% CI: 2.06-6.02 for BNT162b2; RR 2.40; 95% CI: 1.82-3.18 for mRNA-1273). Ulcers appeared a median of 2 days post-vaccination (IQR: 1.25-2.75) and resolved after a median of 12 days (IQR: 7-18). Adolescent females aged 12-17 years had the highest risk (RR vs. age 25-39: 4.01; 95% CI: 2.67-6.05), with a 46.0-fold increased risk (95% CI: 11.2-188.9) compared to age-matched females who received HPV vaccines. CONCLUSIONS: Vulvar ulcers were closely associated with COVID-19 vaccination, especially in adolescent females. While findings suggest a potential link, further research is warranted to determine causality.