Role of ACE2 and Estrogen in COVID-19 Infection
Angiotensin-converting enzyme 2 (ACE2) is a vital enzyme and receptor found on the surfaces of cells, with its highest concentration in the heart, kidneys, lungs, and plasma. Recent studies have revealed that ACE2 plays a crucial role in the entry and invasion of cells by SARS-Cov-2, the virus responsible for COVID-19. Furthermore, ACE2 gene is located on the X chromosome, which has significant implications for disease susceptibility.
In the case of X-linked diseases, having two copies of a gene, as females do, tends to mitigate the effects of the disease. However, males, who possess only one copy of the X chromosome, may experience heightened vulnerability to such diseases. This is particularly relevant to ACE2, as an increased expression of this gene is observed in males.
Moreover, estrogen, a hormone predominantly found in females, has been found to influence ACE2 expression. Estrogen has the potential to reduce inflammation and tissue fibrosis while promoting tissue repair. Consequently, this may contribute to a lower risk of severe complications from COVID-19 in females compared to males.
TMPRSS2 and Androgens: Potential Factors in COVID-19 Severity
It is widely acknowledged by experts that COVID-19 may interact differently with transmembrane serine protease 2 (TMPRSS2) based on sex. TMPRSS2 is a gene commonly associated with prostate cancer, but it also plays a crucial role in the entry and attachment of the virus to cells. Interestingly, the transcription of the TMPRSS2 gene is primarily stimulated by androgens, the hormones responsible for male characteristics.
A remarkable observation is that patients undergoing androgen deprivation therapy for prostate cancer have shown a decreased risk of COVID-19 infection. This finding suggests a potential link between androgen levels and susceptibility to the virus. Moreover, individuals with androgenic alopecia, a condition characterized by male pattern baldness, have been found to be more prone to experiencing severe symptoms of COVID-19. These findings support the notion that males may be at a higher risk of infection compared to females. Furthermore, this could also explain why young children generally exhibit milder symptoms when infected with the virus.