Updated profiling of COVID-19 vaccine adverse events using VAERS case reports

Background Adverse events (AEs) associated with COVID-19 vaccines remain a critical aspect of safety surveillance. In 2022, we reported the first systematic profiling of COVID-19 vaccine AEs using the Vaccine Adverse Event Reporting System (VAERS). Since then, vaccines have evolved with the introduction of bivalent formulations. This study provides an updated analysis to capture evolving safety trends. Methods Building upon our previous analysis, we systematically analyzed AE profiles for the Pfizer-BioNTech, Moderna, and Janssen vaccines, along with the newer bivalent Pfizer-BioNTech and Moderna vaccines and the protein subunit Novavax vaccine, using VAERS data through 28 June 2024. We obtained processed VAERS data via Cov19VaxKB. Significance of each AE was determined using Pearson’s Chi-square test, proportional reporting ratios, and case report frequencies with established thresholds. Overlap and age- or sex-stratified analyses were conducted to characterize shared and unique AE patterns across vaccine types. AE classification using the Ontology of Adverse Events was performed to categorize and interpret significant AEs within a structured hierarchy. Results We observed a marked decrease in unique AEs reported for the Pfizer-BioNTech and Moderna monovalent mRNA vaccines and the recombinant vector vaccine Janssen. The bivalent versions of Pfizer-BioNTech and Moderna exhibited distinct overlapping AE profiles compared to their monovalent counterparts, and bivalent vaccines were generally associated with fewer AEs than the classical monovalent vaccines. Significant differences were observed in thrombosis, myocarditis, and Guillain-Barré syndrome (GBS) across vaccines. Age-specific analyses revealed a bimodal pattern with higher AE reporting in children aged 0–9 and adults aged 50–69, and clear sex differences. Females reported more common AEs, while males were more often linked to serious AEs (thrombosis, myocarditis, and GBS). Death-related AEs were uncommon but more frequent among older males and primarily associated with monovalent formulations. Ontology-based classification revealed that females were more likely to experience sensory-related AEs, whereas males were more prone to cardiovascular-related AEs. Conclusion The adverse event profiles of COVID-19 vaccines during 2020–2024 largely overlapped those identified during 2020–2021, while also revealing new overall and age- and sex-specific AE patterns. Ontology-guided classification enhanced the interpretation of large-scale vaccine safety data, supporting more precise risk assessment across groups.