Sex, gender overlooked in COVID-19 research

Most studies and clinical trials regarding the novel coronavirus disease (COVID-19) fail to consider sex and gender as important variables affecting outcomes, a recent study has found.

The researchers retrieved a total of 4,420 related studies from ClinicalTrials.gov and assessed each according to four degrees of attention they paid to sex/gender: sex/gender treated as an analytical variable, sex/gender matching or representation, addressing sex/gender only during recruitment, and no mention of the variable at all. A separate analysis was carried out for pharmacological randomized controlled trials (RCTs).

Only 21.2 percent (n=935) of the included studies explicitly referred to sex/gender as a criterion for recruitment. Four percent (n=178) took sex/gender as an analytical variable, which involved conducting sex-stratified analyses, explicitly setting it as a covariate, or hypothesizing that sex differences could affect outcomes.

In addition, 5.4 percent (n=237) planned sex-matched or representative samples or emphasized sex/gender during reporting. One hundred studies exclusively enrolled women, mostly focusing on COVID-19 in pregnancy; only one study enrolled people who identified as transgender. Majority (65.7 percent; n=2,906) did not address sex/gender in any part of the protocol.

In a separate analysis of pharmacological RCTs, 45 papers were deemed eligible for inclusion, of which only four (9 percent) adjusted analyses by sex/gender and eight (17.8 percent) provided sex-disaggregated findings.

“Although sex appears to be an important determinant of mortality risk and immunologic responses to COVID-19, currently registered clinical trials mostly omit sex as an explicit recruitment or analytical criterion,” the researchers said.

“Investigating sex differences can highlight otherwise ignored mechanisms and should, hence, be an essential component of robust, reproducible, and socially relevant research,” they added.