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Why are men more likely to die from COVID? It’s complicated.

COVID

“There is no single story to tell about gender differences during this pandemic, even in the United States.”

Charles Krupa / AP image

It is one of the most well-known takeaways of the pandemic: Men die of COVID-19 more often than women do.

Early on, some scientists suspected that the cause was primarily biological and that sex-based treatments for men – such as estrogen injections or androgen blockers – could help reduce their risk of dying.

But a new study analyzing gender differences in COVID-19 deaths over time in the United States suggests the picture is much more complicated.

While men generally died at a higher rate than women, trends varied widely over time and by state, the study found. This suggests that social factors – such as job types, behavioral patterns, and underlying health problems – played a large role in the apparent gender differences, researchers said.

“There’s no single story to tell about gender differences during this pandemic, even in the United States,” said Sarah Richardson, director of the GenderSci Lab at Harvard University, who studies how biological sex interacts with cultural influences in society.

Richardson’s team began collecting gender data on COVID cases and deaths early in the pandemic before the Centers for Disease Control and Prevention began collecting and sharing this information. Her research team logged on every Monday morning, checking each state’s data and maintaining it on a tracker on the lab’s website. The tracker, which runs from April 2020 to December 2021, is the only source of sex-based weekly COVID-19 data by state.

These data enabled researchers to analyze COVID cases and deaths in all 50 states and Washington, DC over a 55-week period.

Nationwide, they found no significant differences in case rates between men and women. But death rates – the number of deaths among men or women divided by the state’s total population of each sex – were often higher among men than women.

How much higher depended on the state and the date. In Texas, for example, men died at a markedly higher rate each week, as the research team analyzed. In New York, men died at a higher rate than women – although the difference was not quite as great as in Texas – in all but three weeks. But in Connecticut, women died more than men in 22 of the weeks analyzed.

“You can have states right next to each other, like Connecticut and New York, that have a completely different pattern but still experienced the same wave,” Richardson said.

Cumulatively over 55 weeks, mortality was slightly higher for women in two states, Rhode Island and Massachusetts. In nine states, including Connecticut, rates were roughly the same. And in the rest of the country, death rates were higher for men.

Gender differences in genes, hormones, or immune responses are not likely to explain these differences, the researchers said.

“There would be no reason for biology to be so variable across time and space,” said Katharine Lee, a biological anthropologist and engineer at Washington University in St. Louis. Louis and author of the new study.

But social and behavioral factors, the researchers said, could help explain many of these patterns.

For example, men are more likely to have jobs in transportation, factories, meat packing, agriculture, and construction – occupations with higher frequencies of COVID-19 exposure and death. Men are also more likely to be imprisoned and experience homelessness, which increases their risk of virus exposure.

Women are more likely than men to report hand washing, mask wearing, and compliance with social distance restrictions, all of which may reduce their risk of becoming infected with the virus. And women are more likely to be vaccinated.

The researchers speculated that states with more public health restrictions could see reduced gender differences. In New York, which saw a significantly higher number of men die in the first six weeks of the pandemic, mortality leveled off when restrictions were introduced. The observed differences in New York can also be partly explained by better data collection as well as underreporting of deaths at long-term care facilities, where the majority of residents are women.

Richardson’s research team did not have access to age data for each gender, an important factor as older people are more likely to die from COVID and different states have different age distributions. Even before COVID, men had a lower life expectancy, possibly driven by higher rates of certain chronic disorders, more risky behaviors, and more dangerous jobs. The “pre-existing mortality gap,” rather than a specific male vulnerability to the virus, could help explain the difference with COVID, Richardson said.

Still, independent experts said the new findings should not lead researchers to completely rule out the role of biology.

“You can’t attribute observations of things like mortality to a complex disease like COVID and say it’s all biology,” said Sabra Klein, a microbiologist and co-director of the Johns Hopkins Center for Women’s Health, Sex and Gender Research. “But I also do not think one can say that it is all social and it is all behavioral.”

Using electronic health records from Johns Hopkins hospitals in Maryland and Washington DC, Klein found that there were higher incidences of severe COVID disease and death among men. However, biostatistic modeling showed that this difference could be significantly explained by greater inflammatory responses among men, suggesting a biological difference.

And in experiments looking at the effects of COVID in hamsters by sex, which may be helpful as they do not include the social factors present in humans, Klein’s group showed that men performed worse. Other studies have also shown that women produce a stronger immune response than men.

Other experts said that access to more detailed data – on factors such as race, income and level of education – would allow researchers to take a more nuanced look at the observed variations in gender differences.

“I think they do a lot with a little,” said Derek Griffith, a public health psychologist and co-director of the Racial Justice Institute at Georgetown University.

“The data sources documenting these differences usually do not have the capacity to help explain them,” he said, pointing to the health effects of stress, financial burdens and discrimination that may underlie racial or gender differences in health outcomes, but which are difficult to quantify.

Griffith said racial differences in COVID outcomes were similarly complex. In the early stages of the pandemic, researchers speculated that black people had a lower risk of getting the virus and possibly had some biological protections, Griffith said. But as data began to show that black people in the United States were at a higher risk of dying from COVID-19 than white people, the pendulum swung the other way, with some scientists speculating on innate genetic differences.

Now, Griffith said, there is greater recognition of the many socioeconomic factors that affect health inequalities. “And yet in both cases, with sex and with race, the kneeling assumption is that it must be biological,” he said.

Richardson’s Harvard group hopes other researchers will use their data sets to analyze the effects of states’ different public health policies.

But other data gaps remain: Studies have shown that long COVID, for example, affects women disproportionately, but the disease is not consistently tracked at the state level. And the researchers did not have data on transgender or gender-non-conforming COVID patients.

“These are not as rich in data as we would like to have to characterize the full gender impact of the COVID pandemic,” Richardson said.

This article was originally published in The New York Times.

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