COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection

Eur J Clin Microbiol Infect Dis. 2021 May;40(5):905-919. doi: 10.1007/s10096-020-04138-6. Epub 2021 Jan 3.


COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells and is highly expressed in the heart, kidneys, and lungs and shed into the plasma. ACE2 is a key regulator of the renin-angiotensin-aldosterone system (RAAS). SARS-CoV-2 causes ACE/ACE2 balance disruption and RAAS activation, which leads ultimately to COVID-19 progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular disease. Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection. This article reviews the existing literature and knowledge of ACE2 in COVID-19 setting and focuses on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.

Keywords: Angiotensin-converting enzyme; COVID-19; SARS-CoV-2; Tissue damage.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2 / genetics
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Antibodies, Monoclonal / therapeutic use
  • COVID-19 / epidemiology
  • COVID-19 / pathology*
  • COVID-19 / therapy
  • Comorbidity
  • Humans
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Polymorphism, Genetic
  • Renin-Angiotensin System / physiology
  • SARS-CoV-2 / pathogenicity*
  • Spike Glycoprotein, Coronavirus / immunology


  • Antibodies, Monoclonal
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

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