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As the first wave of COVID-19 vaccines enter the market, and global immunisation programmes are implemented, the time is right to remind researchers and regulatory agencies of the critical importance of including biological sex as a variable in trial data analysis and reporting.1 The phase 3 Oxford–AstraZeneca trial interim report indicates more participation from women, which the investigators attribute to a recruitment focus on health-care workers,2 but they have not yet reported or discussed how biological sex could influence the data. Future reporting of sex-disaggregated data and a discussion of how sex factors influence the trial outcomes would benefit regulatory and public decision making and the design of mass vaccination programmes.

on health-care workers,2 but they have not yet reported or discussed how biological sex could influence the data. Future reporting of sex-disaggregated data and a discussion of how sex factors influence the trial outcomes would benefit regulatory and public decision making and the design of mass vaccination programmes. Why is biological sex relevant, and sex-disaggregated analysis important? A growing body of research highlights the influence of biological sex in clinically relevant health outcomes, including sex-specific differences in immunity, pharmacology, and vaccines outcomes (side-effects and efficacy).3 In vaccine studies, cisgender females tend to develop higher antibody response and, relatedly, higher efficacy and more side-effects, suggesting the need for sex-differentiated dosing regimens.3, 4 Previous influenza vaccine research suggests that women can produce the same immunological response to half-dose vaccine as men do to full dose.5 According to research findings in preprint,6 sex-based differences in innate and adaptive immunity in SARS-CoV-2 infections are probable contributors to the increased risk of intensive care unit admission and overall mortality in men, and increased reports of long-COVID symptoms in women. These hypotheses and evidence on the sex determinants of immune responses could also be present in COVID-19 vaccine-induced immunity and adverse outcomes.

are probable contributors to the increased risk of intensive care unit admission and overall mortality in men, and increased reports of long-COVID symptoms in women. These hypotheses and evidence on the sex determinants of immune responses could also be present in COVID-19 vaccine-induced immunity and adverse outcomes. Taking a cue from the remarkable achievements in vaccine innovation and research during the COVID-19 pandemic, we have an opportunity to course-correct the integration of biological sex as a core variable in study design, analysis, and reporting. Sex factors, including sex-disaggregated analysis and reporting, are still neglected across the continuum of medicines research and regulation.7 This is also the case in COVID-19 trial data reporting. According to an evaluation in preprint8 of nearly 2500 COVID-19-related studies, less than 5% of investigators had pre-planned for sex-disaggregated data analysis in their studies. We note and applaud those vaccine trial reports that did include sex-disaggregated primary outcomes data.9, 10 A further mention of sex-disaggregated adverse events and secondary outcomes in future reports would be beneficial. This would collectively set an analysis and reporting benchmark not just for the many COVID-19 candidate vaccines in the research pipeline, but also for all future pharmaceuticals, biologics, and other medical interventions. For the Gender and COVID-19 Agenda-setting Initiative see www.ghhbuzzboard.org For the Gender and COVID-19 Agenda-setting Initiative see www.ghhbuzzboard.org