Sex-disaggregated data in COVID-19 vaccine trials

Vijayasingham, Lavanya; Bischof, Evelyne; Wolfe, Jeannette

doi:10.1016/s0140-6736(21)00384-6

Cited by 22 publications

(15 citation statements)

References 11 publications

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“…In this mini review of studies reporting efficacy and/or safety outcomes of vaccines included under COVAX, we found that women and men were equally represented in RCTs, whilst women (and healthcare workers) comprised the majority of participants in observational studies. Despite global calls for the routine disaggregation of COVID-19 data by sex/gender (59)(60)(61)(62), only two RCTs reported efficacy data by sex/gender, and none stratified safety data by sex/gender. Among the 34 included observational studies, 13 (38%) presented all sex/gender-disaggregated data (n =1 (3%) for efficacy and n = 12 (35%) for safety).…”

Section: Overall Summary Of Findingsmentioning

confidence: 99%

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

Vassallo

Shajahan

Harris

et al. 2021

Front. Glob. Womens Health

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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.

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Section: Overall Summary Of Findingsmentioning

confidence: 99%

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

Vassallo

Shajahan

Harris

et al. 2021

Front. Glob. Womens Health

View full text Add to dashboard Cite

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“…Sex-related factors, influencing both the subjects' immunity and the vaccine outcomes, are still neglected in the clinical research, and clinical trials very rarely include a preplanned sex-disaggregated analysis in their study design [4,7].…”

Section: Introductionmentioning

confidence: 99%

Sex Disparities in Efficacy in COVID-19 Vaccines: A Systematic Review and Meta-Analysis

et al. 2021

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Sex differences in adaptive and innate immune responses have been shown to occur and anecdotal reports suggest that vaccine efficacy and safety may be sex-dependent. We investigated the influence of sex on the efficacy of COVID-19 vaccines through a systematic review and meta-analysis of clinical trials on COVID-19 vaccines. The safety profile of COVID-19 vaccines was also investigated. A systematic review included eligible articles published in three databases and three websites. A meta-analysis of available data, stratified by sex, was conducted. Statistical analysis was performed using the Hartung–Knapp–Sidik–Jonkman method, as well as influence and heterogeneity analysis. Pooled analysis showed significantly higher efficacy, measured as the rate of new COVID-19 cases, in men compared to women in the vaccine group (OR = 0.67, 95% CI 0.48–0.94). No sex differences were found in the rate of new cases in the control group (OR = 0.92, 95% CI 0.78–1.09). Safety profiles derived from pharmacovigilance reports appear to indicate increased toxicity in women. In conclusion, evidence of a potential role of sex in COVID-19 vaccine efficacy was described. It strengthens the need to include sex as a core variable in the clinical trial design of COVID-19 vaccines.

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“…This sex-determined gene-dose effect may have important implications for managing the COVID-19 pandemic. While sex-based immunological differences are not new ( 2 ), sex as a biological variable is often neglected in clinical and especially pre-clinical research, especially in inflammatory diseases ( 107 , 108 ). Unfortunately, COVID-19 research is no exception.…”

Section: Discussionmentioning

confidence: 99%

“…Fortunately, two major vaccine trials (Pfizer, Moderna) did include sex-disaggregated primary outcome data. However, further analysis of sex-disaggregated adverse events and secondary outcomes was lacking, which could have set a reporting benchmark for future medical intervention reporting ( 108 ). Sex-disaggregated data are not provided by all countries and clinical reports about infection or mortality rate are often not sex-disaggregated, further complicating sex-specific analyses ( 110 , 111 ).…”

Section: Discussionmentioning

confidence: 99%

“…In various articles calling for investigation of TLR7 agonist or IFN administration early in COVID-19, sex is also not named as a factor to be taken into account ( 22 , 24 , 60 , 78 , 98 , 99 ). This trend is especially surprising considering the gendered hospitalization and mortality rates of COVID-19 and many have called to reverse this ( 1 , 108 , 110 , 112 , 113 ). While several articles noted the possible sex differences in immune response to COVID-19, only few clinical and experimental studies have been conducted to investigate this further ( 70 ).…”

Section: Discussionmentioning

confidence: 99%

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Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19

Spiering

Vries

2021

Front. Immunol.

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A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the gene-dose of Toll-Like Receptor (TLR) 7 could contribute to the sex-skewed severity. TLR7 is one of the crucial pattern recognition receptors for SARS-CoV-2 ssRNA and the gene-dose effect is caused by X chromosome inactivation (XCI) escape. Female immune cells with TLR7 XCI escape have biallelic TLR7 expression and produce more type 1 interferon (IFN) upon TLR7 stimulation. In COVID-19, TLR7 in plasmacytoid dendritic cells is one of the pattern recognition receptors responsible for IFN production and a delayed IFN response has been associated with immunopathogenesis and mortality. Here, we provide a hypothesis that females may be protected to some extend against severe COVID-19, due to the biallelic TLR7 expression, allowing them to mount a stronger and more protective IFN response early after infection. Studies exploring COVID-19 treatment via the TLR7-mediated IFN pathway should consider this sex difference. Various factors such as age, sex hormones and escape modulation remain to be investigated concerning the TLR7 gene-dose effect.

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Sex-disaggregated data in COVID-19 vaccine trials

Cited by 22 publications

References 11 publications

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

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

Sex Disparities in Efficacy in COVID-19 Vaccines: A Systematic Review and Meta-Analysis

Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19

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