Men with COVID-19 three times more likely to need ICU care, study finds

By early June 2020, researchers had begun to notice something consistent in the data: men were dying from COVID-19 at higher rates than women. When scientists examined more than three million confirmed cases across 46 countries and 44 American states—data collected between January and June of that year—the pattern became unmistakable. Men and women were contracting the virus at essentially equal rates, with almost exactly half of all confirmed cases occurring in male patients. But once infected, men faced a starkly different trajectory. They were nearly three times as likely as women to require intensive care, and they were 39 percent more likely to die.

The disparity was not random or limited to a single region. It appeared globally, across nearly every country and state examined, suggesting something fundamental was at work. Kate Webb, a researcher at the University of Cape Town and one of the study's authors, emphasized the clinical importance of this finding. Doctors needed to understand that sex itself was a risk factor—that when a man arrived at the hospital with COVID-19, his biology placed him in a higher-risk category simply by virtue of being male. Yet Webb also noted something troubling about the research landscape: sex was often treated as an afterthought in medical studies, an incidental variable rather than a central one. This analysis was a reminder that it deserved far more attention.

The explanation lay in immunology. Women's immune systems appeared to offer them a natural advantage against severe COVID-19, rooted in biological differences that had nothing to do with behavior or exposure. Women naturally produced higher levels of type I interferon proteins, molecules that help regulate the immune response and prevent the dangerous overreaction known as a cytokine storm—a cascade of inflammation believed to drive the most severe cases of COVID-19. Additionally, the female hormone estradiol seemed to bolster immune defenses by enhancing the activity of T cells, which kill infected cells, and by increasing antibody production. Men, by contrast, carried testosterone, which actually suppressed immune function. The researchers noted that these sex-based differences in immune response had been documented in previous research; COVID-19 simply made them consequential in a new and urgent way.

There were other factors at play as well. Men and women suffered from chronic conditions like hypertension and diabetes at similar rates globally, yet men still faced worse outcomes from COVID-19. The researchers acknowledged that data on how other medical conditions might interact with sex to influence severity was incomplete. The picture was clear enough to matter clinically, but not so complete that every mechanism was understood. What remained certain was that being male carried additional risk.

The findings pointed toward a practical question that would soon become urgent: how would sex differences affect vaccine response? Previous vaccines for other infections had shown that men and women sometimes responded differently to immunization. Whether COVID-19 vaccines would follow the same pattern was still unknown. Webb and her colleagues argued that sex needed to be treated as a serious variable in vaccine research from the outset—not added as an afterthought, but built into study design from the beginning. If vaccines worked differently in men and women, that difference needed to be discovered and understood before rollout, not discovered afterward.