Differences in COVID-19 outcomes related to sex

By Colin Lightfoot, M.Sc. Infection and ImmunityReviewed by Danielle Ellis, B.Sc.May 9 2022

Coronavirus disease 2019 (COVID-19) has caused approximately 386 million cases worldwide, 138 million cases in the United States, 5.7 million deaths worldwide, and over 888,000 deaths in the United States. According to a growing body of research, males with COVID-19 had worse outcomes and death. Males are three times more likely than females to require intensive care unit (ICU) treatment and have a 15% greater death risk.

When infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), males are more likely to develop organ dysfunction such as respiratory failure, acute kidney injury (AKI), and severe gastrointestinal disease. When comorbidities are controlled for, males still have increased morbidity and mortality rates; thus, male sex has been recognized as a risk factor in some clinical trials. 

In a recent review published in the Journal of Comparative Effectiveness Research, researchers looked at gender variations in COVID-19 outcomes such as hospitalization, ICU admission, mortality, and heart damage. Within a context of biological and non-biological causes, they also explore aspects that may lead to sex-based disparities in COVID-19 morbidity and mortality. The authors offer results from multiple studies that include sex-disaggregated datasets filtered mostly by males and females, with no official representation of intersex and transgender people. 

What did they find?

Several studies highlighted the increased risk of hospitalization associated with COVID-19 positive males, even when adjusted for comorbidities and age. In a retrospective, multicenter cohort study that examined the variation in rates of COVID-19 associated hospitalization and/or ICU admissions between males and females, males were shown to have a higher frequency of both. Another study looked at hospitalization rates, viral clearance disparities, and case fatality rates in a group of COVID-19 patients and discovered that males had higher hospitalization rates than females. Females exhibited greater viral clearance than males, but females were in the hospital longer than males.

Mortality rates for hospitalized individuals with severe COVID-19 vary by sex. Males had a 16% higher mortality risk than females, according to a global meta-analysis of 26 studies looking at the impact of sex, age, and numerous other comorbidities on mortality in COVID-19 patients. Males had nearly double the risks of postsurgical 30-day mortality as females, according to multicenter, retrospective cohort research involving individuals with COVID-19 infection who underwent surgery in 235 institutions across 24 countries.

Another study found that while males under 50 years of age needed more ventilator assistance than females, fatality rates were similar between the sexes in this cohort. On the other hand, males above the age of 50 had a higher mortality rate. Even though males have a higher mortality rate from COVID-19, females have a higher risk of long-term COVID-19 symptoms, such as weariness, dyspnea, and greater disability, following COVID-19 hospitalization.

Men are more likely than women to engage in harmful health habits such as smoking and consuming alcohol. SARS-CoV-2 entrance into cells has been linked to increased production of angiotensin-converting enzyme 2 (ACE2) receptors, which could be influenced by smoking. When opposed to females, males have lower compliance with COVID-19 prevention strategies such as social distancing and mask-wearing, according to a recent study. It's worth noting that some professional groups, such as frontline healthcare professionals, are disproportionately female, leading to increased infection exposure and risk. While the overall prevalence of COVID-19 in the overall population is approximately 2%, recent data suggest it is nearer to 5–6% among healthcare professionals. 

The COVID-19 pandemic has had a severe influence on sexual health, and there is evidence that COVID-19 can be spread sexually. According to a recent study, men who engage in sex with men may have comparable rates of sexual activity to pre-pandemic levels; however, rates of sexually transmitted infection and HIV testing and condom use have been falling, presumably due to access. In-person sexual work and activity have decreased as worry about COVID-19 has increased, according to research on sex workers, a primarily female-driven profession.

Implications

The ongoing SARS-CoV-2 pandemic has resulted in the death of millions of people worldwide, disproportionately affecting men. Genetic predisposition, hormone impacts, immune system responses, and non-biological variables such as smoking and alcohol intake contribute to males' greater morbidity and mortality when infected with COVID-19. To improve the development of personalized therapy against SARS-CoV-2, future studies, particularly clinical trials, that include sex as a variable for analysis are needed.