Most COVID-19 studies do not consider sex or gender

COVID-19 affects men and women differently, yet most current clinical studies of SARS-CoV-2 and the disease do not mention sex or gender, according to an international team of researchers.

Only 4% of 4,420 studies of COVID-19 registered with ClinicalTrials.gov explicitly planned to address sex and gender in their analysis, the researchers said. Also, 21.2% accounted for sex and gender in selecting participants, while 5.4% planned to have sex-matched or representative subgroups and samples.

The researchers noted that men and women have responded to COVID-19 differently. Men are more vulnerable to severe disease, more men are hospitalized, and more men die from the effects of the virus, the researchers said.

Why these differences occur is unknown, the researchers said, but they may mean that men and women might need different therapies.

Gender also is connected to infection risk, the researchers continued. For example, women are more commonly employed in positions with client or customer contact or as caregivers, increasing their risk of exposure.

These differences demand attention to sex and gender in the conduct of clinical trials and in planning public health measures, the researchers said, and the lack of consideration of sex and gender is problematic.

“We have seen from the beginning that the disease does not have an identical course for women and men,” study author Sabine Oertelt-Prigione, MD, MSc, of Radboud University and the Medical School of the University of Bielefeld, said in a press release. “The differences in rates of hospitalization and death point to this. This means that our care, such as medicines or other interventions, could also have a different outcome depending on whether the patient is a woman or a man.”

ClinicalTrials.gov is a U.S. database of more than 300,000 studies from 200 countries. The researchers examined 1,659 observational studies and 2,475 intervention studies in their analysis.

According to the analysis, 935 (21.2%) studies explicitly addressed sex or gender solely as a recruitment criterion, and 178 (4%) mentioned sex or gender as a planned analytical variable.

Also, 237 (5.4%) studies planned sex-matched or representative samples (65) or emphasized sex or gender reporting (172). Plus, 124 (2.8%) focused solely on one sex, with 100 recruiting only female subjects and 24 recruiting only males. Female-only studies mostly focused on the relationship between COVID-19 and pregnancy outcomes.

Many studies might not have included data about sex and gender because they were conducted under high time pressure, the researchers said.

“Researchers are sometimes worried that analyzing sex differences in a study might mean more participants and longer recruitment times to reach their targets,” Oertelt-Prigione said. “Especially in the early phases of the pandemic, they were working under lots of time pressure.”

“On the subject of time pressures, we did hope that as the pandemic wore on and more awareness was raised about the sex and gender disparities, we would see more of a focus on sex and gender in the study protocols being registered on ClinicalTrials.gov, but that turned out not to be the case,” study author Emer Brady, PhD, MSc, of the Danish Centre for Studies in Research and Research Policy at Aarhus University, said in the release.

Additionally, the researchers examined published trials, which paid more attention to sex and gender, Brady said. However, only one in four trials included sex or gender in their analyses, Brady continued.

“We increasingly see that men and women respond differently to pharmacological interventions. Ignoring this in trials might lead to serious unwanted side effects later,” said Oertelt-Prigione. “Looking at sex differences has helped us understand the infection better, and it will help us understand our treatment options better. Taking into consideration sex differences is an essential step toward more personalized health care.”

Reference:

Brady E, et al. Nat Commun. 2021;doi:10.1038/s41467-021-24265-8.