Around the world, the death toll from COVID-19 has a stark gender divide: More men are dying with the coronavirus than women. In the United States, government data show men account for a significant majority of all deaths.
But Massachusetts is one of a handful of states that stand as exceptions: Here, women make up nearly 52 percent of all coronavirus-related deaths — a percentage that has steadily ticked up in recent weeks. And among the 10 states with the highest death tolls where COVID-19 fatalities by sex are publicly reported, Massachusetts women make up the biggest share of those who died.
Experts say behavior, biology, and societal factors may all play a part in national disparities in coronavirus deaths between men and women — everything from hand-washing habits to hormones and exposure to infection in certain jobs. Understanding these factors better, they say, could have huge implications for combating the pandemic, both in prevention and in treatment.
In Massachusetts, one key to why the coronavirus has taken a greater toll on women may ultimately be found in these dual truths: They live longer than men on average and therefore populate nursing homes in higher numbers. And it is long-term care facilities here that have been particularly hard hit compared to much of the country, as infections have swept through the Commonwealth.
“Whatever happens in nursing homes is going to sway all our statistics,” said epidemiology professor Lisa Berkman, who directs the Harvard Center for Population and Development Studies at the T.H. Chan School of Public Health.
From a worldwide perspective — where more than 300,000 deaths have been recorded — Massachusetts is an outlier. From China to Italy and Spain, studies have found that men make up a disproportionate share of COVID-19 deaths, compared to women. The pattern has largely held in the United States, where an April study of hospitalization rates from the Centers for Disease Control and Prevention suggested that “males may be disproportionately affected” by COVID-19. Preliminary data gathered by the National Vital Statistics System and reported by the CDC found that men accounted for 55 percent of 54,861 deaths across the country, compared to 45 percent for women.
Researchers have suggested various biological reasons why men might be more vulnerable to COVID-19. To begin with, women typically have more robust immune responses, which could play a role in combating a new virus, they say.
“Immunologically, men and women can often and do mount very different responses, both in terms of the timing of those responses — the tendency for antiviral responses to be more rapid in women than in men — and the magnitude,” said Sabra L. Klein, a professor at the Johns Hopkins Center for Women’s Health, Sex, and Gender Differences.
Some researchers believe the sex hormones estrogen and testosterone may play a part in coronavirus responses, which has led to clinical trials in New York and California in which scientists are treating male patients with female sex hormones.
COVID-19 also enters cells through an enzyme known as the ACE2 receptor, and researchers think biological differences may play a part there, too.
“There is higher expression of ACE2 in males compared to females,” said Kathryn Sandberg, director of the Center for the Study of Sex Differences in Health, Aging and Disease at Georgetown University. She noted that her lab’s result was in animal studies and would need to be confirmed in humans. “But if there's more ACE2 around in a man compared to a woman, then the virus has more chance to grab hold, get into cells, and wreak its havoc.”
Many scientists say that focusing solely on sex-linked biology is simplistic, however. It’s important, they point out, to look at social factors including everyday behaviors that are more common in men than women, and that may now put them at risk.
“For example there’s very well documented differences in gendered behaviors around hygiene in bathrooms,” said Nancy Krieger, professor of social epidemiology at the Harvard T.H. Chan School of Public Health. Studies show “men are much less likely to wash their hands after using the restroom than women are. So that’s going to have implications for infection.”
In addition, “men are often a bit more delayed in seeking health care,” Klein noted, which might influence the course of an illness.
At many stages of life, men already die at higher rates than women, researchers have found, for reasons that can include both biological and lifestyle factors such as smoking, drinking, and risk-taking behavior.
“I think that COVID-19 is exacerbating the death rates of both men and women, and is doing so relative to what their death rates already are,” Krieger said. How it’s amplifying them could be connected to gender-related patterns of health practices and exposures, she explained.
While the pandemic has seen gender disparities in mortality around the globe, “there’s huge variation across localities in the degree of that disparity, with some localities being close to 50-50 and others having a huge excess of male deaths,” pointed out Sarah Richardson, a professor who studies gender and sex in biology as director of the Harvard GenderSci Lab.
That kind of variation suggests the presence of non-biological factors, she says. Based on previous epidemics and pandemics including the Spanish flu, SARS, and MERS, which saw huge numbers of male deaths, she says a key factor could be occupational and environmental exposure. In the Spanish flu, for example, a small subset of men were exposed at much higher rates, including military and working-class men who had to continue working during the pandemic.
Another factor could be serious underlying health problems such as heart disease or diabetes: “Co-morbidities pretty much totally explained the sex difference in outcomes for SARS,” said Richardson, who says that in many instances, men may be entering the coronavirus pandemic in less robust health.
She points to Alabama, one of the few states that release data on pre-existing medical conditions. As of May 4, about 60 percent of COVID-19 deaths in Alabama were men, she said. But when her lab looked only at people with no reported underlying health problems, the percentage of male deaths dropped to 50 percent.
Obtaining a full national picture of sex disparities in COVID-19 deaths is not yet possible, and publicly available data are changing daily. Across the country, slightly more than two-thirds of states reported gender data for coronavirus deaths on their websites, a recent Globe survey found. The vast majority of those, over two dozen states, reported more male deaths as of May 14. Four states were split about 50-50 in male and female deaths.
And six states, including Massachusetts, reported more female deaths than male. Massachusetts had the most deaths among them, at 5,482.
Why are more women dying in those states? The answer may be found in nursing homes. Massachusetts has seen staggering fatalities in its nursing homes the past two months. Nearly 61 percent of the state’s coronavirus deaths were in long-term-care facilities as of May 14, according to the Department of Public Health — a strikingly high rate compared to most of the rest of the country.
A similar pattern exists elsewhere: Among the top 10 states in coronavirus deaths, only Massachusetts, Connecticut, and Pennsylvania reported more female fatalities than male — and all have high nursing home deaths. In Connecticut and Pennsylvania, the share of all confirmed and probable coronavirus deaths linked to long-term-care facilities was 60 and 69 percent, respectively, recent data show.
When a pandemic hits nursing homes particularly hard, the high concentration of vulnerable women gathered in these homes can suffer disproportionately, perhaps to the point of shifting an entire state’s results.
Especially in urban areas, nursing home workers may have two or three jobs in more than one long-term-care facility, so they may spread infection among patients in more than one place, said Berkman. “What I would suspect is that it’s a perfect storm,” she said.
Richardson also suggests that some states may not be fully tallying up their nursing-home coronavirus deaths, and could thus be exaggerating the gender divide.
While male-female disparities in coronavirus deaths may appear striking, researchers say the true picture remains unclear — and critical to study. The answers could unlock solutions for preventing and treating COVID-19, said Dr. Hadine Joffe, executive director of the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital.
In a commentary published in Annals of Internal Medicine, Joffe called on fellow scientists to include factors related to men and women in research related to the coronavirus pandemic.
“Sex and gender should be incorporated at the foundation of science,” Joffe said. “That is optimal for the entire population. If you don’t do that you might miss important factors for disease outcomes and treatment.”