Sex Disparities In COVID Outcomes Aren't Just Biological

Since the start of the pandemic, researchers have observed that males with COVID-19 have worse outcomes than females. The data shows that men tend to get sicker and die from COVID more often than women do.

While there could be innate sex-related biological differences that contribute to the disparity, a new study published in Social Science & Medicine suggests that COVID sex disparities are complex.

What the Researchers Found

For the study, the researchers used 13 months' worth of data from the U.S. Gender/Sex COVID-19 Data Tracker, a project at Harvard's GenderSci Lab. The data was sex-disaggregated, which means that the researchers collected and analyzed data on men and women separately.

The researchers found that while males experienced higher mortality from COVID than females, the trend was not consistent. It varied widely by state and at different points throughout the pandemic.

The study's findings suggest that sex-related biological differences might not be the only driver of the sex disparities researchers have seen in COVID risks and outcomes.

The researchers highlighted that social factors could be as relevant—if not more relevant—than biological sex in shaping COVID disparities.

The Role of Social Factors

Ann Caroline Danielsen, MPH, a researcher at the Harvard GenderSci Lab and one of the study's authors, told Verywell that the study shows that "sex disparities varied significantly between U.S. states and over different phases of the pandemic.

According to Danielsen, that variation "suggests that socio-contextual factors—which vary across time and geography—sizeably modulate the magnitude of sex disparities.”

These context-sensitive social factors, like a person's occupation, health behaviors, and race/ethnicity, also influence sex disparities in COVID to different degrees.

Gender

Health behaviors during the pandemic have been shaped by several factors, including gender. One study found that female retail shoppers were 1.5 times more likely to wear a mask than male retail shoppers.

Women were also more likely than men to comply with public policy measures such as mask-wearing and social distancing restrictions.

These points demonstrate how health behavior affects COVID-19 risk. However, gender-linked differences in structural exposures can be a major influence as well.

Employment

Danielsen pointed out that "men hold the majority of jobs in many of the occupational categories—such as transportation, manufacturing, and agriculture—that have been associated with disproportionate levels of exposure and mortality."

According to Danielsen, that inequality is "likely due to the high levels of face-to-face interactions, inadequate supply of protective equipment, and unfavourable working conditions."

Danielsen added that “gendered social structures, as exemplified by occupation, unevenly distribute the burden of COVID-19 mortality and contribute to the sex disparities that we observe in the data."

However, it's important to note that women disproportionately have jobs in the health care and food industries, as well as teaching professions. This significantly exposes them to COVID.

Location

Aside from gender and employment factors, the study also highlighted regional differences in COVID outcomes.

For example, healthcare, transportation, and construction workers had higher mortality rates in Massachusetts. In California, food and agriculture workers, transportation, and manufacturing workers had the highest increase in mortality.

Additionally, differences in state-level mask mandates and business policies for employees could also affect the variation of the sex disparity at the state level.

Residential settings—including incarceration and homelessness—also contribute.

In the U.S., males make up the majority of unhoused and incarcerated people—groups that are at an increased risk of getting COVID. However, the protective measures for these populations also varied across states.

Beyond Sex-Related Differences

Assuming that only sex-related biological factors contribute to COVID sex disparities would be detrimental to public health.

If this perspective guided our understanding, interventions and research would fail to encompass the whole picture. They would ultimately be insufficient to address the variation in sex disparities or to help us understand it better.

According to Danielsen, one concern is that focusing on sex-related factors alone would "obscure gender-related and other social factors" that could be as relevant—if not more relevant—than biological sex "in shaping vulnerability to COVID-19."

Danielsen added that taking that focus "leads to a unidimensional understanding of sex disparities, independent of social context," which, in turn, "limits opportunities to identify and address the structural variables that underpin such disparities.”

We Can't Ignore Biology

While the study emphasized how socioeconomic factors influence health disparities, it does not mean that we should completely overlook the role of biology.

Sabra L. Klein, PhD, a microbiologist and the co-director of the Center for Women’s Health, Sex, and Gender Research at the Johns Hopkins Bloomberg School of Public Health, told Verywell that if we only focus on biology, "we miss the inequities that also affect COVID outcomes—which is true."

However, Klein added that "swinging the opposite direction and saying that nothing is biologically different between the sexes is equally dangerous and misses the point that biological differences can be modifiers of health and disease.” 

Exploring Biology's Role

Researchers have been looking at the role biology plays in COVID outcomes. A study published in Open Forum Infectious Diseases found that the increased risk of death from COVID among males was associated with too much inflammation early in the course of the disease.

The finding suggested that a sex-specific inflammatory response to a SARS-CoV-2 infection could explain the sex differences in COVID outcomes.

Klein pointed out that if you remove inflammatory measures from the model, then the sex difference in hospitalizations and deaths goes away—which provides a testable hypothesis.

An animal study found that SARS-CoV-2-infected male hamsters had more severe disease and greater morbidity than female hamsters. The male hamsters also had more pneumonia and lower antibody responses associated with recovery.

According to Klein, these examples show that biology does play a role in the sex disparities in COVID outcomes—it’s just not the only piece of the puzzle.

Since we know that socioeconomic variables influence disease risk and outcomes, comprehensive and transparent demographic data needs to be made available to researchers who are exploring how structural inequities affect COVID disparities.

“I hope that our research will encourage deeper reckoning with how gender, alongside multiple other axes of social inequity, features in the broader landscape of the social determinants of COVID-19,” said Danielsen. “I also hope that the variation in sex disparities that we observe across states and time will orient future investigations into the root causes of such disparities.”

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.