According to the Centers for Disease Control and Prevention. In the United States, a gender gap is emerging in vaccination rates, with women ahead of men by 6 percentage points. Further, rare adverse effects from the AstraZeneca vaccine appear to strike women more frequently, whereas those from the Pfizer-BioNTech and Moderna vaccines more often affect young men.
Even the largest COVID-19 trials do tend to skip analysis by sex. For example, the Pfizer-BioNTech and Moderna vaccine trials explored whether vaccine efficacy differed by sex, finding more than 90% efficacy for both men and women. But neither trial broke out adverse effects by sex, as United Nations University gender and health researcher Lavanya Vijayasingham and colleagues noted in a letter in The Lancet in March.
COVID-19 doesn’t strike the sexes equally. Globally, for every 10 COVID-19 intensive care unit admissions among women, there are 18 for men; for every 10 women who die of COVID-19, 15 men die.
But out of 45 COVID-19 randomized controlled trials whose results were published by December 2020, only eight reported the impact of sex or gender, according to a paper published today in Nature Communications. Other recent data show even simple counts of cases and vaccinations are not broken down by sex and gender.
Rare adverse effects from the AstraZeneca vaccine appear to strike women more frequently, whereas those from the Pfizer-BioNTech and Moderna vaccines more often affect young men
Senior author Sabine Oertelt-Prigione, a gender and health researcher at Radboud University Medical Center, was disheartened by her group’s findings. “I would have assumed that [sex] would be picked up in the trials, simply because it’s such an evident piece of the puzzle,” she says.
Skipping that step is potentially dangerous in trials of drugs that may affect men and women differently, given their physiological differences, Oertelt-Prigione says. And it misses an opportunity to learn about the workings of the disease, adds Susan Phillips, an epidemiologist at Queen’s University who was not involved in the study.
Martin Landray of the University of Oxford finds the lack of attention to sex effects surprising, too. He led the United Kingdom’s Recovery trial, which found the anti-inflammatory drug tocilizumab reduces the risk of death from COVID-19 and did explore whether results differed by sex (though it found none worth reporting).
“I just thought that’s what everybody did.” Phillips, however, notes that researchers have often skipped gender analyses in published clinical research for more than 30 years. “The problem remains,” she says. “And this makes the current paper important.”
Oertelt-Prigione’s team searched PubMed for all papers on COVID-19 published before December 15, 2020, excluding commentaries, observational trials, and other studies to identify 45 randomized controlled trials that tested potential treatments and vaccines. All trials in the study reported numbers of male and female participants. But only eight examined whether results differed among men and women, the team found.
Even if these data are not published in a scientific journal, they are still collected and monitored, but low numbers of serious adverse events may mean that significant sex differences have not been detected, says State University of New York Upstate Medical University’s Stephen Thomas, a lead investigator on the Pfizer vaccine trial.
The new paper’s findings are consistent with other studies. A recent, smaller study of COVID-19 trials, published in EClinicalMedicine, found zero out of 30 trials explored whether results were affected by sex. And an April paper in BMJ Global Health that examined a broader range of COVID-19 papers, including observational studies, found only 14 out of 121 analyzed whether sex affected the results.
