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COVID-19 Risk Factors – Gender

There are certain factors that put particular groups of people at higher risk of experiencing severe disease if infected by SARS CoV-2. Click here for an overview.

Characteristics such as gender, age, and weight are collectively known as demographics. These factors play a key role in determining how a person responds following infection with SARS CoV-2. 

This article explores gender in more detail:

The effect of gender

COVID-19 appears to adversely affect the male population more than the female. Men are at increased risk of developing moderate to severe symptoms once infected with SARS CoV-2. Data from China, the US and Europe has all found that men are more likely to be hospitalised with critical symptoms or die following infection with the virus. 

More research is required to understand exactly why females are better protected from SARS CoV-2 than men, but there are some emerging theories:

  • The X chromosome. One plausible explanation is that the X chromosome carries a number of important genes that have an important role in the regulation of the immune system which could offer immunological protection. This is supported by the fact that females have more robust antibody responses following exposure to other pathogens. Theoretically, the reduced susceptibility of females to severe symptoms following viral infection could be attributed to the X chromosome. In males, the presence of a single X chromosome, compared to the two copies that females carry, means that they can be more immuno-compromised under certain conditions.
  • ACE2 receptor. The ACE2 receptor is the enzyme that is allowing the SARS CoV-2 to infect and destroy the cells of the body. Men and women have different levels of ACE2 and it is suggested that this is one of the reasons for their differing susceptibilities. However, this theory is complicated by conflicting data, particularly with regards to levels of ACE2 in the circulation and further work is required to better understand the gender differences in expression levels. 
  • Lifestyle and cultural aspects.  Men are more likely to have pre-existing conditions, such as cardiovascular (CV) disease, than women. Those with CV disease are at greater risk of experiencing severe symptoms. In certain cultures, males are also more likely to smoke and drink alcohol, which are additional risk factors for COVID-19. Questions also need to be asked about the likelihood of males seeking medical assistance for health issues and whether, for some men, they avoid seeking help until their condition is advanced.
  • Male hormones. Very recent work suggests that the male sex hormones (androgens) may increase the susceptibility of males to severe disease. It is possible that testosterone increases the ability of SARS CoV-2 to enter the cells. However, work on this is very preliminary and warrants further investigation.

Sources:

  • Ciaglia, Elena, et al. “COVID-19 Infection and Circulating ACE2 Levels: Protective Role in Women and Children.” Frontiers in Pediatrics, vol. 8, 23 Apr. 2020, doi:10.3389/fped.2020.00206.
  • Gemmati, Donato, et al. “COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-Chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?” International Journal of Molecular Sciences, vol. 21, no. 10, 14 May 2020, p. 3474., doi:10.3390/ijms21103474.
  • Jin, Jian-Min, et al. “Gender Differences in Patients with COVID-19: Focus on Severity and Mortality.” Frontiers in Public Health, 29 Apr. 2020, doi:10.1101/2020.02.23.20026864.
  • Libert, Claude, et al. “The X Chromosome in Immune Functions: When a Chromosome Makes the Difference.” Nature Reviews Immunology, vol. 10, no. 8, Aug. 2010, pp. 594–604., doi:10.1038/nri2815.
  • Oudit, Gavin Y, and Marc A Pfeffer. “Plasma Angiotensin-Converting Enzyme 2: Novel Biomarker in Heart Failure with Implications for COVID-19.” European Heart Journal, vol. 41, no. 19, 10 May 2020, pp. 1818–1820., doi:10.1093/eurheartj/ehaa414.
  • Richardson, Safiya, et al. “Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area.” Jama, vol. 323, no. 20, 22 Apr. 2020, pp. 2052–2059., doi:10.1001/jama.2020.6775.
  • Wadman, Meredith. “Why Coronavirus Hits Men Harder: Sex Hormones Offer Clues.” Science, 3 June 2020, doi:10.1126/science.abd1288.