Clinical trials for COVID-19 should include sex as a variable

The number of COVID-19 cases appears to be comparable between men and women, but the severity of disease and death is two times greater for men than for women. History, including the 1918 influenza pandemic, warned us that male biases in COVID-19 could occur. In this Viewpoint, we focus on biological explanations, with a forward look at why clinicians and biomedical researchers should consider sex as a biological variable that will affect treatment outcomes for COVID-19. There is a long history of not analyzing or reporting differences between women and men in the prophylactic or therapeutic treatment of infectious diseases. We seek to reverse this trend and call on investigators developing and testing therapeutic and prophylactic approaches for COVID-19 to design studies that are inclusive of male versus female differences in drug responses, immunotherapies, vaccines, and nonpharmacological interventions.

Sex- or Gender-specific Differences in the Clinical Presentation, Outcome, and Treatment of SARS-CoV-2.

This review describes the sex and gender differences in COVID-19 presentation, treatment, and outcomes. We discuss the differences between the sexes in susceptibility to infection, the role of sex chromosomes on the body's immunologic response and the influence of hormones on the body's response to the virus. Additionally, the sex differences in clinical and laboratory presentation, complications of infection and outcomes, as well as differences in response to treatment and prevention are reviewed.