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Sex differences in COVID-19: the role of androgens in disease severity and progression

Mohamed S Mohamed1, Thiago C Moulin2, Helgi B Schiöth1,3

  • 1Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala, Sweden.

Endocrine
|November 12, 2020
PubMed

Insights

Men show higher COVID-19 severity due to androgen sensitivity influencing viral entry. Androgen receptor activity impacts SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infectivity, potentially predicting disease progression.

Area of Science:

  • Endocrinology
  • Virology
  • Genetics

Background:

  • Reports indicate higher hospitalization, morbidity, and mortality rates in men during the SARS-CoV-2 pandemic.
  • Sex hormones are hypothesized to influence viral infectivity, but the exact pathophysiology remains unclear.

Purpose of the Study:

  • To review evidence linking androgen sensitivity to COVID-19 disease severity.
  • To explore androgen pathways and related drugs for COVID-19 treatment.
  • To assess androgen sensitivity as a predictor of COVID-19 progression.

Main Methods:

  • Literature review of studies on androgens and COVID-19.
  • Description of drugs targeting androgen pathways for potential COVID-19 treatment.
  • Examination of clinical trials on androgen suppression therapies.

Main Results:

  • The SARS-CoV-2 virus uses Transmembrane protease serine 2 (TMPRSS2) for host cell entry.
  • Androgen receptors promote TMPRSS2 transcription, facilitating viral entry.
  • Androgen receptor gene variants correlate with androgen sensitivity and conditions linked to worse COVID-19 outcomes.

Conclusions:

  • Androgen-mediated TMPRSS2 activity may explain sex-based differences in COVID-19 severity and low pediatric fatalities.
  • Androgen sensitivity is a critical factor for predicting COVID-19 disease severity.
  • Sensitivity tests could aid in patient outcome prediction.
Abstract

Keywords:
CAG repeatsDexamethasoneHydroxychloroquineNitric oxideSARS-COV2Testosterone

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