National Pharmacovigilance Assessment of Oral Adverse Events Following COVID-19 Vaccination in Germany (2020-2023).

OBJECTIVES

Pharmacovigilance efforts for COVID-19 vaccines have largely focused on severe adverse events (AEs), while nonserious, yet distressing, AEs, such as oral AEs, remain underexamined. This study aimed to analyse oral AE reporting patterns in the German national pharmacovigilance database.

METHODS

A retrospective analysis of individual case safety reports (ICSRs) from the Paul-Ehrlich-Institut (PEI) database was conducted for December 2020 to December 2023. The absolute reporting ratio was calculated as cases per 1000 ICSRs for each oral AE. Secondary analyses included: (1) cross-database comparisons with the U.S. Vaccine Adverse Event Reporting System (VAERS); (2) disproportionality analysis using a hybrid approach combining frequentist and Bayesian conditions to establish signals of disproportionate reporting (SDRs); (3) subgroup analyses based on demographic and vaccine-related factors; and (4) multivariable regression to adjust for potential confounders.

RESULTS

Gustatory AEs, such as ageusia and dysgeusia; other oral sensory AEs, including oral paraesthesia and oral hypoaesthesia; and specific mucosal AEs, such as oral herpes and aphthous stomatitis, were the most frequently reported oral AEs in the PEI dataset. Cross-database analysis not only confirmed the prominence of gustatory and other sensory AEs but also highlighted differences, with VAERS reporting higher rates of swollen tongue and lip swelling. Disproportionality analysis identified 21 oral AEs as true SDRs. Female susceptibility was evident in several oral AEs, and age-stratified analysis revealed higher reporting among minors and seniors compared to middle-aged adults. Differences in oral AE reporting between mRNA and viral vector vaccines lacked a consistent pattern, and booster doses were associated with increased reporting of select oral AEs.

CONCLUSIONS

Within the limitations of passive surveillance data, this study highlights the need for further research on oral AEs using self-controlled case-series designs for clinically significant events. Integrating oral AEs into vaccine safety monitoring could improve postmarketing surveillance, while validated AEs may warrant inclusion in product information for transparency.