As the global death toll from the novel coronavirus mounts, evidence is growing that more men than women are becoming seriously ill and dying from the virus. In New York state as of April 9, for example, more than 60 percent of over 6,200 total deaths have been men.

From the early days of the first coronavirus outbreak in China, men were turning up severely ill at a higher rate than women. And this pattern seems to be largely repeating itself if in slightly different numbers in country after country.

Researchers are still not entirely sure why this is. But there are already some intriguing clues.

Could it be higher rates of smoking among men? A higher likelihood of delaying medical care? Or do the answers lie among the genes and sex hormones in our bodies that are setting men on a riskier course if they encounter the virus?

As Marcia Stefanick, a professor of medicine at Stanford University School of Medicine, told the Wall Street Journal, There are profound sex differences in immune systems, and this pandemic is revealing them. But, she noted, What is biology versus what are our social norms and gender behaviors confounds our ability to understand whats going on.

Finding answers could help develop more effective treatment protocols and prevention measures, as well as lead to a more successful vaccine.

One key piece of context for these questions is that there are, in general, a variety of key biological differences in the way men and women fight off infections. Women, for example, tend to mount a stronger immune response. Researchers think this is in part because most women have two X chromosomes, and the X chromosome happens to contain most of the genes related to the immune system (and those with two X chromosomes instead of one also have a wider diversity of immune responses). This extra immune functioning, however, also seems to put women more at risk for autoimmune diseases, such as rheumatoid arthritis and Crohns disease.

Hormones might also help provide women with a more effective defense. Some important immune cells have estrogen receptors, and an estrogen supplement has been shown to increase general immune responses in mice.

A 2017 study in the Journal of Immunology specifically looked into sex differences from the coronavirus that causes SARS (which seems to have killed more men than women during an outbreak in 2003). In that study, researchers found that male mice were more susceptible to the virus. But when they blocked estrogen from working normally in the female mice, the females fell ill at higher rates.

Women might also be more likely to launch an earlier attack on infections in general, saving the body from needing to use all of its virus-fighting might later an event that can skyrocket inflammation and often do more damage to key organs.

These sex patterns are not universal among infections. And data from other viruses, including influenza, sometimes even skews in the other direction, with more women dying than men. Theres still a lot to learn about the novel coronavirus, and so far there arent any studies on it looking specifically at these biological factors. We dont yet know how these biological differences play out for Covid-19, if they do at all. But theyre definitely possibilities.

There are also clues that differences in behavior could be putting men at higher risk for severe Covid-19. It can be a difficult (and time-consuming) endeavor for epidemiologists to untangle behavioral risk factors from one another, so its important to remember that at this point, what we have are correlations that suggest possible risks, not hard proof.

One factor could be smoking rates. A review of existing research as of March 17 concluded that smoking is most likely associated with the negative progression and adverse outcomes of Covid-19. There are a couple of reasons this could be the case, the World Health Organization notes. One is that smokers are more likely to have lung disease, which is an established risk factor for severe infection. The other is that when smoking, a person is more likely to touch their mouth or face, possibly allowing the virus an easy path in.

And smoking is often more common among men than women. According to a 2017 analysis in the Journal of Epidemiology & Community Health, 54 percent of Chinese adult men smoked tobacco, compared with just 2.6 percent of Chinese women. The World Bank reports that, as of 2016, about 41 percent of South Korean men smoked versus about 6 percent of women. (Spain also shows the same general trend, as does the US, but the sex difference isnt as large as it is for China and South Korea.)

Because the research on all of this is so new, it will still probably be some time before we have a clear understanding of what role smoking might play.

Other broad social and cultural variations among genders (that, to be sure, are not universal) might be further exacerbating this trend. For example, in the US, various studies show that men wash their hands less often and are less likely to seek care earlier in an illness. A March 24 poll from Reuters revealed that a smaller percentage of men than women were taking warnings about the coronavirus seriously including changing their behavior.

In this pandemic, the information being reported around the world varies widely. And due to continued lack of testing and increasing concern about deaths being underreported, we still do not have a complete picture of how sex is playing out as a risk factor for the disease and how that might be different in different countries. (Some governments, including the US, are not even reporting cases by sex.) Despite the fuzzy details, however, the pattern is holding steady.

Analysis of data from about 2,000 patients during Chinas main outbreak, from December through February, showed that about 60 percent of patients were men. And Chinas Center for Disease Control reported a fatality rate of 2.8 percent for men versus 1.7 percent for women.

In South Korea, men were actually far less likely to be confirmed to have Covid-19, according to a March 31 paper in Clinical Infectious Diseases. There, just 38 percent of patients were male. But, according to that analysis, men were about twice as likely to die from the disease (1.19 percent for men versus 0.52 percent for women).

In Spain, men and women comprise about an equal number of Covid-19 cases, as the countrys Health Ministry reported on April 3. But men were more than twice as likely to wind up in the ICU and more likely to die (making up almost two-thirds of deaths).

An April 6 study of the hard-hit region of Lombardy, Italy, found that 82 percent of patients admitted to the ICU were men. And in Italy overall, about 70 percent of people dying from coronavirus have been male.

The US CDC isnt releasing coronavirus case breakdowns by sex at this time (it also doesnt prominently feature this data for other infectious diseases, like influenza). This is an additional blow to those who are trying to understand this rapidly spreading illness because the US now has by far the largest number of cases.

Some US states have released sex breakdowns, however. A Washington Post report found that of 13 states that have substantial outbreaks and are reporting these details, men make up a larger number of deaths. As an emergency department nurse told the Post, In general, Ive seen more male patients. And when they do come in, they are at a sicker state. (Recent US data also shows concerning patterns of racial disparities.)

Learning more about how the virus impacts men and women could help determine the most effective treatment for individual patients. For example, it might point to different or earlier interventions in men, or more targeted public health messaging for people who might be more likely to delay seeking care.

Better understanding the nuances of mens and womens immune response to the virus could also be crucial to developing a good vaccine. There are well-documented differences in vaccine effectiveness among men and women, with women tending to be better protected after vaccination. So it will be especially important to ensure that sex is taken into account when designing and analyzing vaccine trials in both animal studies and human ones.

Although men seem to be dying at slightly higher rates than women, everyone is at risk even the young.

There are also some factors that might put some women more at risk. For example, in the US, 76 percent of health care workers are women, according to the US Census Bureau. That means they are at the forefront of this pandemic, coming into contact with potentially infected people on a daily basis.

Additionally, digging deeper into the data reveals other emerging trends in subpopulations. For example, according to an April 2 report from the Italian government, in those 90 and older, women were more likely to die from Covid-19 than men. And, although the overall numbers are small, it seems as though women with certain risk factors (including heart failure, hypertension, and dementia) were more likely to die from Covid-19 than the men who had those conditions.

What has become clear from all this data is that we still have a lot to learn about why some cases of Covid-19 end in respiratory failure or death, or severe illness, and some dont regardless of a persons sex. And we all still have the responsibility to reduce our own odds of getting the virus, and of it spreading to others. It remains crucial for everyone to do their part (washing hands, maintaining social distancing, etc.) to keep the virus from spreading.

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Coronavirus deaths: Why is the virus killing more men than women? - Vox.com

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