Do sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression explain increased severity and mortality of COVID-19 in males?

Diagnosis (Berl). 2020 Nov 18;7(4):385-386. doi: 10.1515/dx-2020-0054.

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), shares similarities with the former SARS outbreak, which was caused by SARS-CoV-1. SARS was characterized by severe lung injury due to virus-induced cytopathic effects and dysregulated hyperinflammatory state. COVID-19 has a higher mortality rate in men both inside and outside China. In this opinion paper, we describe how sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression may explain the increased severity and mortality of COVID-19 in males. We highlight that immunomodulatory treatment must be tailored to the underlying immunobiology at different stages of disease. Moreover, by investigating sex-based immunobiological differences, we may enhance our understanding of COVID-19 pathophysiology and facilitate improved immunomodulatory strategies.

Keywords: ACE2; COVID-19; coronavirus; gender; immunology.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antiviral Agents / pharmacology
  • Betacoronavirus / drug effects
  • CD4 Lymphocyte Count / statistics & numerical data
  • COVID-19
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / mortality*
  • Coronavirus Infections / therapy
  • Coronavirus Infections / virology
  • Cytokines / metabolism
  • Female
  • Humans
  • Immunomodulation
  • Interferon-alpha / drug effects
  • Interferon-alpha / immunology
  • Lymphopenia / mortality
  • Male
  • Membrane Glycoproteins / genetics
  • Mice
  • Models, Animal
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / mortality*
  • Pneumonia, Viral / therapy
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Sex Factors
  • Toll-Like Receptor 7 / genetics

Substances

  • Antiviral Agents
  • Cytokines
  • Interferon-alpha
  • Membrane Glycoproteins
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2