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

Abstract

BackgroundAlbeit 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.MethodsPatient 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.ResultsThe 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.DiscussionThe 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.

Short-term side effects of BNT162b2 vaccine in primary care settings in Qatar: a retrospective study

“…Notably, females demonstrated a heightened probability of encountering side effects with nearly double the likelihood compared to males for both local and systemic side effects. This aligns with findings from other studies ( 53 , 54 ). Clinical data highlights the impact of gender on the frequency and severity of vaccination-related adverse reactions, including fever, pain, and inflammation ( 55 ).…”

Incidence and clinical characteristics of adverse neurological events and stroke-like syndrome associated with immune stress-related response after COVID-19 vaccination in 2021 from Thailand

“…The current study revealed that most neurological AEFIs were more common in female with dyslipidemia, hypertension and diabetes mellitus in all three vaccine types, this finding is consistent with Dutch study which reported 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 [10] . The most frequent clinical complaints of neurological AEFIs were numbness, headache and dizziness which are usually mild, short-duration, and self-limiting, similar to most studies [9] , [10] , [11] , [12] , [13] . Neurological AEFIs can be presented as the sole complaint or co-occurring with systemic AEFIs.…”

Real-world Nuvaxovid COVID-19 vaccine safety profile after first 100,000 doses in Australia, 2022-2023

“…We demonstrated slightly higher overall AEFI reporting for females, particularly those aged 30–49 years of age. Sex disproportionality was expected in observed rates of injection site reaction, paresthesia, nausea and vomiting, consistent with pre-licensure studies[26, 27]. However, we also identified disproportional reporting in females for anaphylaxis, which has not been previously reported for Nuvaxovid, although a similar disproportionality had been noted by Somiya et .…”