According to data from more than 20 countries, men are twice as likely as women to die of COVID-19. In some countries, such as Italy, 70% of deceased coronavirus patients are men. And it’s not just fatalities, men are also getting severely ill at a higher rate than women, suggesting that being male may be a risk factor in itself. Scientists are still not sure why this is the case but there are some clues, from lifestyle choices to testosterone exposure.

Men may be more susceptible to infections in general

Researchers affiliated with Global Health 50/50, an academic research group, analyzed demographic data on COVID-19 deaths in various countries. Overall, they found that men are between 50% and 80% more likely to die from the coronavirus than women.

“Data so far provides no clear pattern in terms of who is more likely to become infected with COVID-19. However, it shows that among confirmed cases, men are consistently dying at a higher rate across countries where data is available,” the report reads.

For instance, in China, Spain, and Germany, men represent just under 65% of total coronavirus deaths. There was no country in over 20 included in the analysis where a higher share of women died because of the virus than men.

The CDC has yet to release coronavirus case breakdowns by sex in the US. However, we know that in New York City, there have been 43 COVID-19 deaths for every 100,000 men in the city, compared with 23 such deaths for every 100,000 women.

“I’m in the emergency room, and it’s remarkable — I’d estimate that 80 percent of the patients being brought in are men,” Dr. Hani Sbitany, a reconstructive surgeon at Mount Sinai Health Systems who has been treating COVID-19 patients in Brooklyn, told The New York Times. “It’s four out of five patients.”

What can explain this?

Scientists have known for a while that there are some sex differences in immune system function. However, there are also gender-specific risky behaviors (i.e. smoking, alcohol) and social norms that make it difficult to tease apart biology from environmental factors.

This is an important question to answer nevertheless. If there are indeed gender-specific immune responses to COVID-19, effective treatment might require differentiation between men and women.

Hormones

Estrogen and testosterone might be responsible for important differences in how an individual’s immune system responds to coronavirus infections.

Studies on mice show that estrogen supplements increase general immune responses, perhaps because immune cells have estrogen receptors. Another study on mice investigated the effects of the coronavirus that caused the 2003 SARS outbreak, finding that male rodents were more susceptible to the virus. When estrogen was blocked from binding to receptors in female mice, the females fell ill at higher rates.

Testosterone, the primary male sex hormone, seems to have a suppressive effect on the immune system. Studies show that when men have infections, their testosterone levels decrease. This may be due to the body trying to divert energy away from taxing actions such as muscle building, sexual appetite, and risk-taking behavior.

A 2014 analysis of the immune response to influenza vaccination found that men with high levels of testosterone produced the lowest number of antibodies.

“These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females,” the authors of this study noted.

Most recently, research suggests that COVID-19 reduces testosterone levels in men by altering the function of the gonads, perhaps increasing disease severity in the process.

However, the role of testosterone becomes complicated once you consider age, which is a major risk factor for COVID-19 for both genders. As men age, their testosterone decreases, but they still get very sick with infections.

In order to really tell the role of testosterone in immune function, an investigation that analyzes both innate and adaptive immunity in a variety of men from different backgrounds would be required. Such an investigation doesn’t exist yet.

Risky male behavior

There are of course behavioral differences between sexes. Smoking is much more prevalent in men than in women, which puts individuals at risk of developing lung cancer, as well as other chronic diseases. In China, 54% of adult men smoke compared to just 2.6% of Chinese women.

Men are also less likely to wash their hands as often as women and are less likely to seek care early when sick. Although there is no study yet to suggest this, men might also be more likely to not wear face masks or use them improperly.

Even before COVID-19, there were important differences in lifespan between men and women. About 57% of all those ages 65 and older are female and by age 85, 67% are women. The average lifespan is about 5 years longer for women than men in the U.S., and about 7 years longer worldwide.

Although the incidence of obesity and old age is generally higher among women, the case fatality rate among infected men with COVID-19 is still higher even when adjusting for these factors, further sowing confusion.

Why understanding sex differences for COVID-19 is important

If men are truly more susceptible to coronavirus infections than women, male patients may require different and earlier interventions. During vaccine development, the nuances in male-female immune response would also require consideration.

There is still much to learn, that’s for sure.

If men truly are more susceptible to coronavirus infections than women, male patients may require different and earlier interventions. During vaccine development, the nuances in male-female immune response would also require consideration.

There is still much to learn, that’s for sure.

It’s also worth noting that although there seem to be some sex-specific differences, virtually everyone is at a significant risk of developing very severe forms of COVID-19 — men and women, young and old. As a result, everyone should practice great caution as the pandemic unfolds going forward.