Male predisposition to severe COVID-19: Review of evidence and potential therapeutic prospects

Area of Science:

• Immunology
• Endocrinology
• Virology

Background:

• Severe COVID-19 exhibits significant sex disparities, with higher incidence and fatalities in males.
• Females may possess a more robust immune response, potentially due to hormonal influences.
• Cytokine storm, a hallmark of severe COVID-19, is implicated in disease progression.

Purpose of the Study:

• To explore the roles of the immune system, sex hormones (estrogen and androgens), and the angiotensin-converting enzyme (ACE) system in the male predisposition to severe COVID-19.
• To elucidate the mechanisms behind differential immune responses between sexes.
• To identify potential therapeutic strategies targeting these systems.

Main Methods:

• Review of existing literature on COVID-19, immunology, endocrinology, and the ACE system.
• Analysis of the impact of sex hormones on immune cell activation and inflammation.
• Exploration of therapeutic interventions based on hormonal modulation and ACE inhibition.

Main Results:

• Estrogen appears to modulate the immune system, offering protection against severe inflammation and COVID-19 in females.
• Androgens are linked to immune cell over-activation, cytokine storm, and heightened inflammation, potentially predisposing males to severe disease.
• The ACE system's role in sex-based COVID-19 severity is also under investigation.

Conclusions:

• Sex hormones play a crucial role in the differential susceptibility and severity of COVID-19 between males and females.
• Therapeutic strategies such as androgen deprivation therapy, estrogen-based treatments, and ACE inhibitors warrant further investigation for managing severe COVID-19.