A large self-controlled study using Dutch primary care records found a small, short-term increase in shingles risk within 28 days of an mRNA COVID-19 booster, with no elevated risk after the primary vaccine series.

Reporting in Drug Safety, first author Rana Jajou, PhD, of the Netherlands Pharmacovigilance Centre Lareb, and colleagues said that the findings help clarify previously conflicting evidence regarding shingles risk after COVID-19 immunization.

For the study, investigators analyzed electronic health record data from more than 2 million vaccinated individuals aged 12 years and older, drawn from 2 large Dutch general practice databases and linked to the national COVID-19 vaccination registry. They used a self-controlled cohort design to compare each individual’s risk of a first general practitioner (GP) consultation for herpes zoster during a predefined post-vaccination risk window (28 days) with their own risk during all other observed periods in 2021. This design controlled for fixed confounders such as age, sex, and comorbidities, while models were additionally adjusted for SARS-CoV-2 infection as a time-varying factor.

Across the cohort, 10,385 individuals (0.5%) consulted their GP for herpes zoster during follow-up. When all COVID-19 vaccine doses and types were analyzed together, vaccination was associated with a modest but statistically significant increase in herpes zoster risk (adjusted incidence rate ratio [IRR], 1.07; 95% CI, 1.02–1.13). However, this signal was largely attributable to the third, or booster, dose. The adjusted IRR following a third dose was 1.21 (95% CI, 1.05–1.38), whereas no increased risk was observed after the first or second doses.

Stratification by vaccine platform showed that the association was confined to mRNA vaccines. For recipients of Pfizer-BioNTech or Moderna vaccines, the adjusted IRR was 1.21 (95% CI, 1.05–1.40) after the third dose, while no excess risk was detected after the primary series. No participants in the dataset received 3 doses of a viral vector vaccine, precluding direct comparison for boosters in that group. Further stratification by individual vaccine brand attenuated the association, with no statistically significant increase seen for Pfizer-BioNTech alone.

Analyses by age and sex did not identify consistent high-risk subgroups. An increased risk was observed among male recipients of viral vector vaccines, but this finding was isolated and not replicated across other strata.

The authors note that the modest increase observed after booster vaccination may reflect short-term immune modulation following repeated antigen exposure, potentially allowing reactivation of latent varicella-zoster virus. They emphasize that the absolute risk increase was small and should be interpreted in the context of the substantial benefits of COVID-19 vaccination, particularly for older adults and patients with chronic disease.

They also noted that shingles can recur, and an initial episode raises the risk of subsequent episodes. “Therefore, only the first episode of herpes zoster was treated as the outcome of interest in this study by excluding persons who consulted their general practitioner for herpes zoster in the 5 years prior to cohort entry,” the authors wrote.“Investigating the risk of recurrence of herpes zoster after COVID-19 vaccination was not part of our study design.”

This study was part of a project which received funding from the Ministry of Health, Welfare and Sport. One of the study authors disclosed having received research funding from Pfizer unrelated to this work and 2 others are editorial board members of Drug Safety.

Source: Drug Safety