Abstract
COVID-19 symptoms and mortality are largely due to its devastating effects in the lungs. The disease is caused by the SARS (Severe Acute Respiratory Syndrome)-CoV-2 coronavirus, which requires host cell proteins such as ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) for infection of lung epithelia. The expression and function of the steroid hormone receptor family is important in many aspects that impact on COVID-19 effects in the lung – notably lung development and function, the immune system, and expression of TMPRSS2 and ACE2. This review provides a brief summary of current knowledge on the roles of the steroid hormone receptors [androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), mineralocorticoid receptor (MR) and oestrogen receptor (ER)] in the lung, their effects on host cell proteins that facilitate SARS-CoV-2 uptake, and provides a snapshot of current clinical trials investigating the use of steroid receptor (SR) ligands to treat COVID-19.
Highlights
The COVID-19 pandemic potentially has a degree of gender bias in terms of infection and mortality rates
Manipulation of steroid receptor (SR) activity may play a key role in mediating severe acute respiratory syndrome (SARS)-CoV-2 infections and ligands such as anti-androgens have therapeutic potential for the disease
Summary
The COVID-19 pandemic potentially has a degree of gender bias in terms of infection and mortality rates. In response to the COVID-19 pandemic, there has been an increase in the number of publications investigating how both male and female sex hormones control various aspects of lung biology and function, as well as their potential roles in regulating genes/proteins within host cells that are essential for viral infection. It is possible that GR activity, aside from modulating the immune system, may influence ACE2 and TMPRSS2 expression in lung cells with potential to affect SARS-CoV-2 uptake/infection. As there is documented cross-talk between GR and AR, there is the possibility of dexamethasone inhibition of AR expression/function and testosterone production [137,138,139] How this AR–GR cross-talk translates to lung tissue and COVID infection is not currently known, though emerging preclinical data suggest that simultaneously targeting both receptors may be of benefit [140]. Spironolactone, which has anti-MR activity, is currently being used in two clinical trials (NCT04826822, NCT04643691), but results are yet to be reported
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