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Review
. 2023 Jan 30:14:1078736.
doi: 10.3389/fimmu.2023.1078736. eCollection 2023.

Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature

Janneke W Duijster  1 , Thomas Lieber  1 , Silvia Pacelli  1   2 , Leontine Van Balveren  1 , Loes S Ruijs  1 , Monika Raethke  1 , Agnes Kant  1 , Florence Van Hunsel  1
Affiliations
Review

Sex-disaggregated outcomes of adverse events after COVID-19 vaccination: A Dutch cohort study and review of the literature

Janneke W Duijster et al. Front Immunol. .

Abstract

Background: Albeit the need for sex-disaggregated results of adverse events after immunization (AEFIs) is gaining attention since the COVID-19 pandemic, studies with emphasis on sexual dimorphism in response to COVID-19 vaccination are relatively scarce. This prospective cohort study aimed to assess differences in the incidence and course of reported AEFIs after COVID-19 vaccination between males and females in the Netherlands and provides a summary of sex-disaggregated outcomes in published literature.

Methods: Patient reported outcomes of AEFIs over a six month period following the first vaccination with BioNTech-Pfizer, AstraZeneca, Moderna or the Johnson&Johnson vaccine were collected in a Cohort Event Monitoring study. Logistic regression was used to assess differences in incidence of 'any AEFI', local reactions and the top ten most reported AEFIs between the sexes. Effects of age, vaccine brand, comorbidities, prior COVID-19 infection and the use of antipyretic drugs were analyzed as well. Also, time-to-onset, time-to-recovery and perceived burden of AEFIs was compared between the sexes. Third, a literature review was done to retrieve sex-disaggregated outcomes of COVID-19 vaccination.

Results: The cohort included 27,540 vaccinees (38.5% males). Females showed around two-fold higher odds of having any AEFI as compared to males with most pronounced differences after the first dose and for nausea and injection site inflammation. Age was inversely associated with AEFI incidence, whereas a prior COVID-19 infection, the use of antipyretic drugs and several comorbidities were positively associated. The perceived burden of AEFIs and time-to-recovery were slightly higher in females.

Discussion: The results of this large cohort study correspond to existing evidence and contribute to the knowledge gain necessary to disentangle the magnitude of the effect sex in response to vaccination. Whilst females have a significant higher probability of experiencing an AEFI than males, we observed that the course and burden is only to a minor extent different between the sexes.

Keywords: COVID-19 vaccine; adverse event after vaccination; longitudinal cohort design; patient reported outcome; pharmacovigilance; sex.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Forest plot of the odds of experiencing an adverse event after immunization (AEFI) in females versus males after dose 1 and dose 2, based on multivariable logistic regression. The size of the square corresponds to the inverse of the standard error. aOR: adjusted odds ratio. Inj.: injection. * p<0.05, **p<0.01, ***p<0.001. (A). Adjusted for: sex, age group, confirmed prior COVID-19 infection, preventive use of antipyretic drugs. (B). Adjusted for: sex, age group.
Figure 2
Figure 2
Distribution of the burden classes among males and females among different adverse events following immunization (AEFIs), based on data of the first dose and all vaccine brands combined. Inj.: injection.
See this image and copyright information in PMC

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References

    1. Kant A, van Hunsel F, van Puijenbroek E. Numbers of spontaneous reports: How to use and interpret? Br J Clin Pharmacol (2022) 88(3):1365–8. doi: 10.1111/bcp.15024 - DOI - PubMed
    1. Rolfes L, Härmark L, Kant A, van Balveren L, Hilgersom W, van Hunsel F. COVID-19 vaccine reactogenicity–a cohort event monitoring study in the Netherlands using patient reported outcomes. Vaccine. (2022) 40(7):970–6. doi: 10.1016/j.vaccine.2022.01.013 - DOI - PMC - PubMed
    1. EMA . Guideline on good pharmacovigilance practices (GVP) - annex I - definitions (Rev 4). (2017). EMA/873138/2011 Rev 2, 6/144.
    1. Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. The how’s and what’s of vaccine reactogenicity. NPJ Vaccines (2019) 4(1):1–11. doi: 10.1038/s41541-019-0132-6 - DOI - PMC - PubMed
    1. Kant A, Jansen J, van Balveren L, van Hunsel F. Description of frequencies of reported adverse events following immunization among four different COVID-19 vaccine brands. Drug safety (2022) 45(4):319–31. doi: 10.1007/s40264-022-01151-w - DOI - PMC - PubMed

Publication types

Grants and funding

The Dutch Ministry of Health, Welfare and Sport granted the funding for the cohort event monitoring of COVID-19 vaccine safety (grant number: 331.880).