Men and COVID-19: A Biopsychosocial Approach to Understanding Sex Differences in Mortality and Recommendations for Practice and Policy Interventions

Derek M. Griffith, PhD; Garima Sharma, MD; Christopher S. Holliday, PhD, MPH; Okechuku K. Enyia, MPH; Matthew Valliere, MPA; Andrea R. Semlow, MS, MPH; Elizabeth C. Stewart, DrPH, MSPH; Roger Scott Blumenthal, MD


Prev Chronic Dis. 2020;17(7):e63 

In This Article

Factors Affecting COVID-19 Morbidity and Mortality Among Men

Although epidemiological data show a difference between men and women in the rates of mortality among those diagnosed with COVID-19, the mechanisms underlying sex differences in mortality are unclear.[3,10,15] Because most health patterns are the result of a combination of biological, behavioral, and psychosocial factors, we must consider how sex-associated biological factors and gender-associated psychosocial and behavioral factors interact in determining health[14] and in explaining COVID-19–associated mortality.[4,8,15] In this section, we first describe biological factors and then discuss psychological and behavioral factors associated with men's higher risk of COVID-19–associated mortality.

Biological Factors

Men and women differ in both innate and adaptive immune responses, perhaps related in part to sex-specific inflammatory responses resulting from X-chromosomal inheritance. The X chromosome contains a high density of immune-related genes; therefore, women generally mount stronger innate and adaptive immune responses than men.[3] This differential regulation of immune responses in men and women is contributed by sex chromosome genes and sex hormones, including estrogen, progesterone, and androgens. Sex-specific disease outcomes after viral infections are attributed to sex-dependent production of steroid hormones, different copy numbers of immune response X-linked genes, and the presence of disease susceptibility genes.[3]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2) for entry into the host cell.[16] The S spike of the virus attaches to the cellular ACE2 receptor (coded by the ACE2 gene) located on the respiratory epithelial cells. The internalization of the virus is potentiated by the cellular protease TMPRSS2 (transmembrane protease, serine 2) in the host cell.[17,18] The high burden of illness and high case-fatality ratio in patients with COVID-19 may be driven in part by the strong affinity of the virus for ACE2, leading to virus entry and multisystem illness in pulmonary, gut, renal, cardiac, and central nervous systems.[16]

Men have higher plasma ACE2 levels than women do, and a recent study of patients with heart failure showed that plasma ACE2 concentrations were higher than normal in men and higher in men than in women, possibly reflecting higher tissue expression of the ACE2 receptor for SARS-CoV infections.[19] This could explain why men might be more susceptible to infection with, or the consequences of, SARS-CoV-2. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Further investigation into the association of ACE2 enzyme activity in COVID-19 and its correlation with sex is ongoing. Although biological factors clearly help to explain the sex difference in COVID-19 mortality, psychosocial and behavioral factors also play a part.

Psychosocial and Behavioral Factors

In addition to sex differences in immune responses, hormones, and genes, there are also psychological, social, and behavioral components that influence COVID-19 progression.[1,15] Compared with women, men tend to engage in more high-risk behaviors that generate potential for contracting COVID-19.[1,4] Polls taken early in the first wave of COVID-19 cases in the United States show sex differences in the perceived severity of the pandemic.[20] Another US study found that men have been more likely to downplay the severity of the virus's potential to harm them,[21] and fewer men than women have reported that they have been avoiding large public gatherings or avoiding close physical contact with others.[21–23] In addition, compared with women in many countries, including the United States, men tend to have higher rates of behaviors that are linked with COVID-19 infection and mortality, including higher rates of tobacco use and alcohol consumption.[1,4,21,24]

Men also tend to have lower rates than women of handwashing, social distancing, wearing masks, and effectively and proactively seeking medical help.[1,4,21,25,26] Many men have been socialized to mask their fear, and it is important to consider how hiding fear affects men's response to COVID-19.[27] It is particularly important to focus on men who respond to threats like COVID-19 with aggression and anger. Research shows that people with this response "tend to downplay risk and are resistant to risk reduction policies," which is problematic during efforts to promote social distancing and other pandemic restrictions.[27] These socially constructed behaviors reduce the perception of susceptibility and severity, which then translates into a decrease in the practice of preventive measures, such as handwashing, and protests against pandemic-related restrictions.

Other factors may intersect with sex and gender, such as age and geography.[28] For example, a US study of associations between perceived risk and worry with age and gender found that although older men perceived their risks of COVID-19 to be higher than those of younger men, older men made the fewest behavior changes across age and gender groups.[29] Another study highlighted the importance of considering place or geography. In a comparison of counties where populations were predominantly Black or predominantly White, the SARS-CoV-2 infection rate was 3 times higher and the death rate was 6 times higher in counties where the population was predominantly Black.[30] In urban areas with high percentages of Black residents with low socioeconomic status, some problematic narratives have emerged that blame the men and women who live in these areas for their high rates of COVID-19 rather than the policies or structures that create these conditions.[31]

In addition to these psychological and behavioral factors, differences in occupational risk exist between men and women. In the United States, a larger number of women than men are deemed essential workers primarily because of the large share of women employed as social workers and in health care.[32] Nevertheless, the low-skilled or low-paid occupations that are considered essential workers (eg, food processing, transportation, delivery, warehousing, construction, manufacturing), where men outnumber women, seem to be associated with a greater risk of mortality.[32]

In summary, a range of biological, psychological, and behavioral factors can explain why men have higher rates of COVID-19–associated morbidity and mortality than women. Although it is critical to identify the factors associated with increased risk for men of COVID-19 mortality, it is equally important to determine how to reduce the risk of men dying of COVID-19.[1,4] The factors that exacerbate men's risk also are intertwined with race, ethnicity, geography, and other proxies for factors that are markers of marginalization and social inequality.[4,14] In the remainder of this commentary, we will discuss selected examples of what can be done, and is being done, to reduce men's risk of COVID-19–associated mortality (Table).