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. 2025 Dec 11.
doi: 10.1007/s40264-025-01638-2. Online ahead of print.

GP Consultations for Herpes Zoster After COVID-19 Vaccination: A Self-Controlled Cohort Study Based on Electronic Health Record Data from the Netherlands

Rana Jajou  1 , Eugène van Puijenbroek  1   2 , Jetty Overbeek  3 , Karin Hek  4 , Erik Mulder  1 , Florence van Hunsel  5   6 , Agnes Kant  1   7
Affiliations

GP Consultations for Herpes Zoster After COVID-19 Vaccination: A Self-Controlled Cohort Study Based on Electronic Health Record Data from the Netherlands

Rana Jajou et al. Drug Saf. .

Abstract

Background and objective: Several systematic reviews and meta-analyses have been published with conflicting results on the risk of herpes zoster after coronavirus disease 2019 (COVID-19) vaccination. We aimed to study the risk of herpes zoster after COVID-19 vaccination using electronic health record data of general practices, from a large cohort in the Netherlands.

Methods: Persons aged ≥ 12 years who received at least one COVID-19 vaccination and were registered in the general practice databases of PHARMO and Nivel Primary Care Database were included. This study used a self-controlled design comparing the risk of herpes zoster in the risk period (28 days after COVID-19 vaccination) with the control period. Poisson regression was used to calculate incidence rate ratios, adjusting for severe acute respiratory syndrome coronavirus 2 infection.

Results: There were 2,098,683 COVID-19 vaccinated persons aged ≥ 12 years included, of whom 1,058,646 (50.4%) were female. An increased risk for herpes zoster was found after all the doses grouped together and the third dose of all COVID-19 vaccination (adjusted incidence rate ratio: all doses 1.07, 95% confidence interval [CI] 1.02-1.13 and third dose 1.21, 95% CI 1.05-1.38). After stratification on vaccine type, all doses and the third dose of messenger RNA vaccination (adjusted incidence rate ratio: all doses 1.06, 95% CI 1.00-1.12 and third dose 1.21, 95% CI 1.05-1.40) showed an increased risk.

Conclusions: Our study showed a slight increased risk of herpes zoster when taking into account all doses and all types of vaccines. After stratification on vaccine type, no increased risk of herpes zoster after the primary vaccination series and a slightly elevated risk after the third/booster vaccination with a messenger RNA vaccine were found.

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Conflict of interest statement

Declarations. Conflict of interest: The authors Rana Jajou, Erik Mulder and Agnes Kant have no conflicts of interest. Karik Hek received funding from Pfizer for research (starting per 01 December 2024) not related to this study. Jetty Overbeek is an employee of the PHARMO Institute for Drug Outcomes Research. This independent research institute performs financially supported studies for government and related health care authorities and several pharmaceutical companies. Florence van Hunsel and Eugène van Puijenbroek are Editorial Board members of Drug Safety. These authors were not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethics approval: All data were anonymized before it was received for data-analyses. For observational studies containing no directly identifiable data, it is not obligated to obtain approval by a medical ethics committee (Dutch Civil Law, Article 7: 458). The study was approved according to the governance code of Nivel-PCD (nr. NZR-00322.008) and by the institutional review board of STIZON, Utrecht, the Netherlands (nr. CC2022-13). Informed consent: For observational studies containing no directly identifiable data, it is not obligated to obtain informed consent from patients (Dutch Civil Law, Article 7: 458). Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and materials: Data for this study are not publicly available in order to protect patient privacy . Inquiries about the data used can be sent to the corresponding author. Code availability: R codes cannot be made available due to the data protection policy for this study. Author’s contributions: All authors (RJ, EP, JO, KH, EM, FH and AK) contributed to the design of the study; RJ and EM performed the data-analysis. All authors contributed to the interpretation of data for the work; FH and RJ drafted the work; All authors contributed to reviewing it critically for important intellectual content; All authors read and approved the final version; All authors are in agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

References

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