Sex and Gender in COVID-19 Vaccine Research: Substantial Evidence Gaps Remain

Abstract

Since the start of the COVID-19 pandemic there has been a global call for sex/gender-disaggregated data to be made available, which has uncovered important findings about COVID-19 testing, incidence, severity, hospitalisations, and deaths. This mini review scopes the evidence base for efficacy, effectiveness, and safety of COVID-19 vaccines from both experimental and observational research, and asks whether (1) women and men were equally recruited and represented in vaccine research, (2) the outcomes of studies were presented or analysed by sex and/or gender, and (3) there is evidence of sex and/or gender differences in outcomes. Following a PubMed search, 41 articles were eligible for inclusion, including seven randomised controlled trials (RCTs), 11 cohort studies, eight cross-sectional surveys, eight routine surveillance studies, and seven case series. Overall, the RCTs contained equal representation of women and men; however, the observational studies contained a higher percentage of women. Of 10 studies with efficacy data, only three (30%) presented sex/gender-disaggregated results. Safety data was included in 35 studies and only 12 (34%) of these presented data by sex/gender. For those that did present disaggregated data, overall, the majority of participants reporting adverse events were women. There is a paucity of reporting and analysis of COVID-19 vaccine data by sex/gender. Research should be designed in a gender-sensitive way to present and, where possible analyse, data by sex/gender to ensure that there is a robust and specific evidence base of efficacy and safety data to assist in building public confidence and promote high vaccine coverage.

Psychiatric adverse reactions to COVID-19 vaccines: A rapid review of published case reports

“…Both sexes appear to be equally affected; no clear preponderance could be made out probably owing to the limited number of reports. Prior cohort studies and reviews have reported an association between female sex and adverse effects after COVID vaccination ( Beatty et al, 2021 , Vassallo et al, 2021 ); this has been explained by higher vaccine reactogenicity among women and the role of hormonal, microbiota, and genetic responses ( Venkatakrishnan et al, 2021 ).…”

Serological Response to SARS-CoV-2 Messenger RNA Vaccine: Real-World Evidence from Italian Adult Population

“…Sex differences in immune response have been explained by the hormonal milieu that can have profound effects on B-cell activity regulation, antibody production and vaccine efficacy, with an elevated level of estradiol associated with higher vaccine-induced immunity [32]. Current data on SARS-CoV-2 vaccination are not sufficient to draw definitive conclusions on sex differences in vaccine efficacy, as reported in a recent review of 41 experimental and observational studies in which Vassallo, A. et al explained the failure to recognize the gender difference through a lack of attention to sex/gender-specific evidence in the design of COVID-19 vaccine research [33].…”

Gender Differences in Adverse Events Following the Pfizer-BioNTech COVID-19 Vaccine

“…In a recent study on the 75 clinical trials on different types of COVID-19 vaccines, 24% reported their main results disaggregated by gender, and only 13% mentioned the implications of their study for females and males [14]. In a mini review of studies reporting safety outcomes of COVID-19 vaccines, the authors found a significant lack of gender-disaggregated evidence across studies [15].…”