Why sex and gender need to be considered in COVID-19 research
A guide for applicants and peer reviewers

First, sex-disaggregated data reveal that more males are dying from COVID-19 than females. It is not clear if there are biological factors at play, or if comorbid and behavioural factors are to blame.

Second, pandemics can compound existing inequalities for girls, women, sexual and gender minorities and other at-risk populations. It is essential that these different subpopulations are considered in order to create effective, equitable policies and interventions.

Applicants and reviewers should appropriately account for the following in COVID-19 research proposals:

Molecular Mechanisms of Viral Pathogenesis

  • Include both male and female cells, as the SARS-CoV-2 receptor, ACE2, is X-linked and escapes X chromosome inactivationFootnote 1. Disaggregate results by sex.

Host Immune Response

  • Include male and female animals or humans, as sex hormones were shown to regulate the host immune response to SARS-CoV infection in miceFootnote 2. Disaggregate results by sex.

Diagnostic Tests and Serologic Antibody Testing

  • Sensitivity and specificity should be tested for males and females separately, as sex differences in viral titers and IgM/IgG antibodies have been reported for viral infections in humans and miceFootnote 3Footnote 4.

Vaccines and Therapeutics

  • Sex-specific dosing of vaccines and other therapeutics should be tested, as efficacy, safety and toxicity for males and females differ for some drugs, immunotherapiesFootnote 5 and vaccinesFootnote 6.

Clinical Trials

  • Stratify randomization by sex, as there are known sex-specific differences in the safety and efficacy of drugs and biologicsFootnote 7. Disaggregate results by sex.

Medical Devices and Personal Protective Equipment

  • Sex-specific anatomical differences and gendered user preferences should be incorporated into the design of medical devices and personal protective equipment for COVID-19.

Social, Behavioural Observational and Seroprevalence Studies

  • Sex, gender, age and other identity characteristics should be considered in survey questions and sampling strategy. Gendered behaviours should be investigated in studies of disease susceptibility. For example, men are more likely to smoke than womenFootnote 8 and less likely to seek healthcareFootnote 9, whereas older women are more likely to live alone and experience social isolation.
  • Gender roles should also be considered. 70% of the paid and unpaid global healthcare workforce are womenFootnote 10, and they face a greater risk of infection being on the frontline of the COVID-19 pandemic.
  • Gender relations should be factored into research on the impact of the pandemic, as physical distancing puts women and girls at higher risk of domestic violence due to heightened tensions in the householdFootnote 11.

Mental Health

  • Mental health effects may reasonably vary by sex, gender, sexual orientation and other identity characteristics, as the triggers, causes, signs and symptoms of depression and anxiety may differFootnote 12.

Implementation Science

  • Sex, gender and other identity characteristics influence the way in which an implementation strategy works, for whom, under what circumstances and why. Messaging should consider how to appropriately include and target different groups according to sex, gender and other identity characteristicsFootnote 13.

Policy

  • The unintended outcomes of all COVID-19 policies, especially economic recovery policies, should be considered for groups such as Indigenous Peoples, sexual and gender minorities, racialized individuals, single parents, immigrants, unpaid workers, individuals with precarious work status, people with disabilities, the homeless and those living in rural and remote areasFootnote 14.
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