As the coronavirus sweeps across the globe, one pattern remains consistent: Men seem harder hit by the virus than women and are more likely to have severe illness or die.
At least in the United States, however, it seems that men are less likely to seek out testing for the virus when they feel sick.
"This is to all of our men out there, no matter what age group: If you have symptoms, you should be tested and make sure that you are tested," Dr. Deborah Birx, the White House's coronavirus response coordinator, said on Thursday.
Data from around 1.5 million tests done in the U.S. show that the majority of people tested, 56%, were women. Of those women, 16% tested positive for the virus. In contrast, only 44% of the tests were done on men. And 23% of them tested positive.
"It gives you an idea about how men often don't present in the health-care delivery system until they have greater symptomatology," said Birx – that is, until they're showing more signs of disease.
That's a concern because experts believe this virus poses more dangers for men, perhaps because of biological differences between men and women.
Sabra Klein, a researcher at the Johns Hopkins Center for Women's Health, Sex, and Gender Differences, began noticing hints of a sex difference in COVID-19 infections back in February as reports began to emerge from China. She knew that an increased risk to men has been observed for other severe coronaviruses that have appeared in the past.
"What I was seeing was a pattern that held true in the SARS outbreak that occurred in Hong Kong," she says, "as well as the ongoing MERS outbreak in the Middle East."
One large study of 44,672 confirmed COVID-19 cases done by the Chinese Center for Disease Control and Prevention, for example, found that the fatality rate was 2.8% for men compared with only 1.7% for women.
While some initially suggested that the much higher rate of cigarette smoking among men in China might be to blame, Klein doubts that explanation.
"What we saw in Wuhan has been replicated in every country around the world where we have accurate reporting," says Klein. "In countries like Spain, where the percentages of males and females who report smoking is not significantly different, we still are seeing this profound male bias in severity of COVID-19."
In Italy, one study of 1,591 cases of critically ill people who were admitted into intensive care units showed that about 82% of them were men.
And a study of people hospitalized in the U.S. for COVID-19 in March similarly found that "males may be disproportionately affected by COVID-19 compared with females."
Public health information from the city of New York, which has one of the world's largest outbreaks, shows that men are more likely to be hospitalized and are nearly twice as likely to die. The city's department of health reports about 39 female deaths per 100,000 people and 71 male deaths per 100,000 people.
Scientists know that, in general, women tend to have greater and more robust immune responses. This can be a double-edged sword; autoimmune diseases are more common in women. But it may mean that women are more protected against novel invading germs.
"My hypothesis would be, maybe females are actually mounting an initial immune response to a greater degree than our male counterparts," says Klein, who has just been awarded funding from the National Institutes of Health to study the biological differences between men and women who are infected with COVID-19.
Studies of HIV and hepatitis C show that women can have a stronger immune reaction to viruses. "There are examples. There are not a lot. And I think part of that is because this has been a grossly understudied area," says Klein.
Women have often been excluded from biomedical research, she explains. Historically, that was meant to protect women of childbearing age who might be pregnant, but over time it became scientific dogma that men and women's bodies, other than their reproductive systems, basically weren't that different.
But sex hormones like testosterone and estrogen seem to be important in modulating the immune response, says Veena Taneja of the Mayo Clinic, who studies differences in male and female immune systems.
What's more, she says, women also have two copies of the X chromosome, while men have only one.
"The X chromosome has lots of immune-response genes," Taneja says.
While women's extra X chromosome is generally silenced, she says, "almost around 10% of those genes, they can be activated. Many of those genes are actually immune-response genes."
That makes it possible, she says, that women get a "double-dose" of protection — although it's still too soon to know exactly how all this might play out in the context of COVID-19.
What is clear, however, is that being male may be a risk factor just like other traits that might make one more vulnerable — for example, being older or having certain medical conditions like asthma or heart disease.
All of this may be why Birx felt compelled to deliver a special message to men during her daily briefing at the White House, saying, "I see a lot of men in the audience today. I just want to remind them about the importance of health care."