Gender-based differences in coronavirus disease 2019: Hormonal influencers of severe acute respiratory syndrome coronavirus receptors and immune responses

Coronavirus disease 2019 (COVID-19) became a pandemic due to a high rate of infection by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2). People with comorbidities such as cardiovascular diseases, Type II diabetes, and COPD have been having acute symptoms and higher rate of mortality. Further, increased severity and lethality of SARS-CoV-2 infection has been observed among men than in women. SARSCoV-2 infects human cells by binding to angiotensin-converting enzyme 2 (ACE2) through its spike protein (S-Protein). ACE2 is a critical transmembrane protein of the renin-angiotensin-aldosterone system which modulates the cardiovascular system and fluid homeostasis. This article reviews the current knowledge about the mechanisms of sex-based differences that may cause variations in COVID-19 susceptibility and outcomes among males and females. Males have been shown to have a delayed viral clearance due to increased retention of coronavirus as compared to females. Recent studies indicate that a severe infection with SARS-CoV-2 impairs spermatogenesis in males, however, the mechanisms by which SARS-CoV-2 damages testicular cells need more studies. We discuss here the distinctive features such as sex hormone milieu, receptor biology, and immunology that may be responsible for the gender-based differences in the outcome of COVID-19.