Certain health habits, as well as sex hormones, may play a role.

By Claire Gillespie
Updated April 28, 2020
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Back in February, the Chinese Center for Disease Control and Prevention published the largest and most comprehensive study of coronavirus cases to date. One of the findings shows a disparity between men and women—although both sexes have been infected in roughly equal numbers, the death rate among men was higher. Of the 72,314 cases studied, 2.8% of infected men died, compared to 1.7% of women. 

Although we don’t have as much COVID-19 data to go on in the US, more than a dozen states and cities that report deaths by sex, such as New York City, Michigan, and Washington, have found a similar disparity. Slightly more women are getting infected with the new coronavirus, but the majority of fatal cases are in men. 

The difference between male and female fatalities mirrors findings following analysis of the SARS and MERS outbreaks, which were also caused by coronaviruses. And during the influenza pandemic of 1918, which killed an estimated 50 million people, adult men were more likely to die than women. 

Clearly, there’s precedent here. But nobody knows exactly why COVID-19 is killing more men than women. 

“The sex differences that we see in mortality from COVID-19 reflects one of the many things we still don’t fully understand about this disease,” Ryan Steele, DO, an assistant professor of clinical medicine in rheumatology, allergy and immunology at Yale School of Medicine, tells Health. “In general, males tend to have a larger number of conditions that are associated with poorer outcomes in COVID-19 such as cardiovascular disease and diabetes.”

However, the increased prevalence of these diseases in men may only be part of the answer. “We see that even among individuals without known health issues and in children, males have worse outcomes,” Dr. Steele says. “This would indicate that the underlying differences in the immune response among genders may play a larger role than we have appreciated so far.”

The notion that female hormones may be protective in some way has led to a new line of research. As the New York Times reported, a clinical trial at Stony Brook University on New York's Long Island will compare use of an estrogen patch among men and older women who have COVID-19 (or are presumed to have the illness) versus a control group to see whether the hormone makes a difference. Separately, according to the Times, Cedars-Sinai Medical Center in Los Angeles will begin a study of progesterone, another female sex hormone, in men with COVID-19.

Females tend to have a more robust immune response than men in fighting infectious diseases, Dr. Steele says. And it’s possible that hormones play a part. While the male sex hormone testosterone suppresses inflammation, the female sex hormone estrogen can activate the cells involved in antiviral responses. In a 2016 study published in American Journal of Physiology, nasal cells were treated with estrogen-like compounds before being exposed to the influenza virus. Only the cells from females responded to the hormones and fought off the virus. 

There's another theory that men are more at risk—both of infection and death—because rates of smoking are higher in men than in women, Bhanu Sud, MD, an infectious disease specialist with St. Jude Medical Center in Orange County, California, tells Health. 

Notably, nearly 50% of men smoke in China, but less than 3% of women do, according to a 2019 article published in Translational Lung Cancer Research

There’s no shortage of data showing that people who smoke are more likely to develop chronic lung and heart diseases, which automatically puts them in the Centers for Disease Control and Prevention (CDC)’s “high risk” group for COVID-19. The CDC also says that smoking is one of the conditions that cause a person to become immunocompromised, which means their immune defenses are weakened. 

Another study from China, published in the New England Journal of Medicine on February 28, found that smokers made up about 26% of those who ended up in intensive care or died of the new coronavirus. When it comes to contracting the virus in the first place, it’s possible that smokers are at a greater risk because of regular hand-to-mouth contact. Plus, they may share contaminated cigarettes.

Dr. Sud points out that immunity is a complex issue, with many factors. “A person’s immunity is based on age, whether they smoke, drink alcohol, or take drugs, as well as other medical issues and what medications they are taking,” he says. “For example, if someone is on chemotherapy, they are more prone to infection—any infection, not just the new coronavirus.” 

Genetics also plays a role, says Dr. Sud, but there is “a lot more analysis to do.” 

Scientists may not have all the answers to the multitude of questions surrounding the new coronavirus, but the data that’s coming in is helping to form a clearer picture.

“We are now beginning to understand that a lot of the complications of COVID-19 are from an exaggerated inflammatory response that follows the initial damage after infection,” says Dr. Steele. “This delicate balance of clearing the infection and modulating the immune response to prevent further damage, taking into account underlying health conditions and biologic differences such as gender, will likely prove crucial in developing effective treatments for COVID-19.” 

The information in this story is accurate as of press time. However, as the situation surrounding COVID-19 continues to evolve, it's possible that some data have changed since publication. While Health is trying to keep our stories as up-to-date as possible, we also encourage readers to stay informed on news and recommendations for their own communities by using the CDCWHO, and their local public health department as resources.

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