Why are men more likely to succumb to Covid-19?

Sex differences in genes, hormones or immune responses are not likely to explain the differences but social and behavioural factors can, researchers said

It’s 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 the reason was primarily biological, and that sex-based treatments for men — like estrogen injections or androgen blockers — could help reduce their risk of dying.

But a new study analysing sex differences in Covid-19 deaths over time in the United States suggests that the picture is much more complicated.

While men overall died at a higher rate than women, the trends varied widely over time and by state, the study found. That suggests that social factors — like job types, behavioural patterns and underlying health issues — played a big role in the apparent sex differences, researchers said.

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

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

That data enabled the researchers to analyse Covid-19 case rates and deaths across all 50 states and Washington, DC, over a period of 55 weeks.

Nationally, they found no significant differences in case rates between men and women. But the 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.

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

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Sex 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 that variable across time and space,” said Katharine Lee, a biological anthropologist and engineer at Washington University in St. Louis and an author of the new study.

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

For example, men are more likely to have jobs in transportation, factories, meatpacking plants, agriculture and construction — occupations with higher rates of Covid-19 exposure and fatalities. Men are also more likely to be incarcerated and to experience homelessness, increasing their risk of virus exposure.

Women are more likely than men to report hand washing, mask wearing and complying with social distancing restrictions, all of which may lower their risk of contracting the virus. And women are more likely to be vaccinated.

Still, independent experts said the new findings should not lead researchers to entirely discount the role of biology.

“You can’t attribute observations about things like mortality from 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 don’t think you can say it’s all social and it’s all behavioural, either.”

Using electronic health records from Johns Hopkins hospitals in Maryland and Washington DC, Klein found that there were higher rates of severe Covid-19 illness and death among men. But biostatistical modelling showed that this disparity could be substantially accounted for by greater inflammatory responses among men, suggesting a biological difference.

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And in experiments looking at the effects of Covid-19 in hamsters by sex, which can be useful since they don’t include the social factors present in humans, Klein’s group showed that males fared worse. Other studies have also shown that women produce a stronger immune response than men.

Other experts said that having access to more granular data — on factors like race, income and education level — would enable the researchers to take a more nuanced look at the observed variations in sex differences.

“I think they’re doing 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 that document these differences don’t usually have the capacity to help explain them,” he said, pointing to the health effects of stress, financial burdens and discrimination that might underlie racial or gender differences in health outcomes but are difficult to quantify.

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