Men More Likely To Be Infected With SARS-CoV-2, Have Worse Outcomes

Men appear to be more susceptible to SARS-CoV-2 infection, and to have worse outcomes across all adult age groups, a new study finds.

An analysis of data from nearly 100,000 Texans tested for the virus found that the positivity rate was higher among men. Among hospitalized patients, men were more likely than women to experience pulmonary and extra-pulmonary complications, and more likely to die, according to the results published in PLoS ONE.

"Our findings are in line with studies of COVID-19 in China that found that the disease disproportionately affects men and women," write the authors, led by Farhaan Vahidy of the Houston Methodist Research Institute, in Texas. "Understanding sex differences in disease severity, clinical characteristics and mortality is a fundamental step for improved disease management, prediction of poor outcomes and intervention strategies for both men and women."

The underlying mechanisms or drivers of the observed sex differences are yet to be determined, the researchers add.

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The authors were unable to comment for this story by press time.

To explore whether men might be at greater risk of infection and worse outcomes from COVID-19, Vahidy and his colleagues turned to data from the Houston Methodist COVID-19 Surveillance and Outcomes Registry. Houston Methodist is an eight-hospital tertiary healthcare system serving the diverse greater Houston population.

The researchers extracted data from electronic medical records for male and female individuals of all races and ethnicities aged 18 and older who were tested for the virus between March 6 and August 22, 2020, by nasopharyngeal swab with specimens tested via PCR.

In their analysis, the researchers included sociodemographic factors (age, race, marital status, insurance, Zip-code-based median income and population density), behavioral factors (smoking), and comorbidities (body mass index, hypertension, hyperlipidemia, asthma, myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, liver disease, renal disease, diabetes with our without complications, paraplegia/hemiplegia, cancer, and HIV/AIDS).

Of the 96,473 individuals included in the analysis, 15% tested positive for the virus. After adjusting for sociodemographic factors and comorbidities, the researchers found that men had a higher likelihood of SARS-CoV-2 positivity compared to women (adjusted odds ratio 1.39). Similarly, men were more likely than women to need ICU care (aOR 1.36), mechanical ventilation (aOR 1.3), and to die in the hospital (aOR 1.44).

It's not surprising that men are having worse outcomes, said Dr. Umesh Gidwani, an associate professor of medicine at the Icahn School of Medicine at Mount Sinai and director of the cardiac ICU at The Mount Sinai Hospital in New York City.

"For the longest time we have known that male sex is associated with a higher risk for having poorer outcomes with infectious diseases across all ages," Dr. Gidwani said. "And as early as April of 2020, the Chinese were reporting a higher incidence of pneumonia, ICU admission and dying in men."

What's not known at this point is exactly why men are more susceptible and have worse outcomes than women, Dr. Gidwani said. Other research on the immune systems of men and women has shown that women have higher T-cell activity when they encounter a virus and a greater ability to raise the number of B cells circulating in the body, he added.

But it's also possible that gender-related behavioral factors come into play, Gidwani said, adding that research has shown that women at a population level are more cautious and aware of dangers and therefore tend to be more likely to follow guidelines that men may dismiss.

Sabra Klein agreed that at least part of the difference in outcomes might be traced to differences in the way male and female immune systems function.

It might be that men's immune systems, because they can't mount as strong of a response to the virus as women's can, start to become dysregulated, said Klein, a professor of molecular microbiology and immunology at the Johns Hopkins School of Public Health, in Baltimore.

An interesting finding with the new study was that the researchers did not see an interaction between sex and age, Klein said. "Pretty much adult men of any age were more likely than women to experience severe outcomes," she added.

Klein would like to see scientists explore "the next frontier, that is looking at the intersection between sex and race and ethnicity. It may not be that all men at all ages are equally likely to be hospitalized. It may be that in Caucasian men it's true only among those who are older, for example."

—Linda Carroll

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