Late-Onset Maculopapular Eruptions Associated with Elevated Varicella-Zoster Virus Complement-Fixing Antibody Titers following BNT162b2 mRNA COVID-19 Vaccination in Older Adult Japanese Patients: A Cross-Sectional Study

Abstract

Diverse cutaneous adverse reactions associated with the messenger RNA-based BNT162b2 coronavirus disease 2019 (COVID-19) vaccine have been reported, usually developing within 3 weeks after the first vaccination. However, the long-term cutaneous effects of this vaccine remain poorly understood. We hypothesized that the BNT162b2 vaccine might trigger late-onset (>4 weeks after the first dose) maculopapular eruptions associated with elevated varicella-zoster virus (VZV) complement-fixing antibody (VZV-CF Ab) titers indicative of recent subclinical VZV reactivation. Therefore, we conducted a hospital-based cross-sectional study at the Dermatology Department of Kita-Harima Medical Center, Ono City, Japan, between July 1, 2021, and June 30, 2022, to investigate the correlations among the BNT162b2 vaccine, maculopapular eruptions, and VZV-CF Ab titers. Fifteen eligible patients (EPs) who experienced maculopapular eruptions on the trunk and extremities no earlier than 4 weeks after the first BNT162b2 vaccine dose and 12 control patients (CPs) were enrolled. The mean age of EPs and CPs was 73.7 and 77.6 years, respectively, and the median interval between the first BNT162b2 vaccination and onset of maculopapular eruptions was 90 days. The median VZV-CF Ab titer of EPs was significantly higher than that of CPs (×8 vs. ×4). Although people of all ages, except children aged ≤12 years, received BNT162b2 vaccinations, all EPs were aged ≥57 years. All EPs presented between July 2021 and March 2022. There were no EPs from April 2022 to December 2023. These results suggest that the BNT162b2 vaccine triggers elevated VZV-CF Ab titer-associated maculopapular eruptions as late-onset cutaneous adverse reactions in older adults. Furthermore, the observation that two EPs concurrently experienced delayed large local reactions, also known as COVID arm, along with maculopapular eruptions, supported our hypothesis. Our findings may improve the diagnosis of BNT162b2 vaccine-triggered elevated VZV-CF Ab titer-associated late-onset maculopapular eruptions and facilitate further investigation of diverse BNT162b2 vaccine-induced adverse events.