Adverse events following influenza immunization: understanding the role of age and sex interactions

ABSTRACT

Background

Reduction of adverse events following immunization (AEFI) could improve vaccine uptake. Evidence suggests sex and age affect AEFI rates but, with limited understanding of their interaction, groups at higher risk for adverse reaction cannot be identified.

Research Design and Methods

Using deidentified data (n = 308,481) from Australians receiving influenza vaccinations in the 2020 calendar year, we analyzed the effects of independent predictors (i.e. age and sex), on experiencing an AEFI using logistic regression generalized additive modeling to capture any nonlinear relationships and adjusting for vaccine brand and concomitant vaccination.

Results

The overall reaction rate was 5.5%. Modeling revealed significant effects of age (p < 0.001), sex (p < 0.001), and age × sex (p < 0.001). Females were more likely than males to experience AEFIs between 7.5 and 87.5 years of age and exhibited peak odds at about 53 years, while peak odds for males occurred in infancy.

Conclusion

The results suggest there is a need for targeting AEFI reduction in females, particularly in 30–70-year-olds, to improve the vaccination experience. The results further suggest that reducing concomitant vaccination and choosing less reactogenic vaccine brands could reduce risk of AEFI, however, retaining concomitant vaccination may optimize vaccine uptake.

KEYWORDS:

• Aging
• diurnal
• influenza
• reactogenicity
• sex difference
• vaccination

Acknowledgments

The authors acknowledge the technical assistance provided by the Sydney Informatics Hub, a Core Research Facility of the University of Sydney.

Declaration of Interests

A Leeb and I Peters are affiliated with SmartVax, the organization providing the data; involvement was limited to data collection and provision and comment on methods and synthesis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

KM Edwards conceived and with E Bohn-Goldbaum, co-designed the study; A Leeb and I Peters acquired data; T Cross and E Bohn-Goldbaum led the analysis and, with KM Edwards, the interpretation of data. E Bohn-Goldbaum drafted the article, and all authors critically revised it for intellectual content before approving the final version for submission.

Supplemental data

Supplemental data for this article can be accessed here.

Additional information

Funding

The manuscript was funded by the Financial Markets Foundation for Children [grant number 2014–233].