Organ-protective Effect of Angiotensin-Converting Enzyme 2 and Its Effect on the Prognosis of COVID-19

J Med Virol. 2020 Jul;92(7):726-730. doi: 10.1002/jmv.25785. Epub 2020 Apr 5.


This article reviews the correlation between angiotensin-converting enzyme 2 (ACE2) and severe risk factors for coronavirus disease 2019 (COVID-19) and the possible mechanisms. ACE2 is a crucial component of the renin-angiotensin system (RAS). The classical RAS ACE-Ang II-AT1R regulatory axis and the ACE2-Ang 1-7-MasR counter-regulatory axis play an essential role in maintaining homeostasis in humans. ACE2 is widely distributed in the heart, kidneys, lungs, and testes. ACE2 antagonizes the activation of the classical RAS system and protects against organ damage, protecting against hypertension, diabetes, and cardiovascular disease. Similar to SARS-CoV, SARS-CoV-2 also uses the ACE2 receptor to invade human alveolar epithelial cells. Acute respiratory distress syndrome (ARDS) is a clinical high-mortality disease, and ACE2 has a protective effect on this type of acute lung injury. Current research shows that the poor prognosis of patients with COVID-19 is related to factors such as sex (male), age (>60 years), underlying diseases (hypertension, diabetes, and cardiovascular disease), secondary ARDS, and other relevant factors. Because of these protective effects of ACE2 on chronic underlying diseases and ARDS, the development of spike protein-based vaccine and drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the future.

Keywords: acute respiratory distress syndrome (ARDS); angiotensin-converting enzyme 2 (ACE2); coronavirus disease 2019 (COVID-19); renin-angiotensin system (RAS); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Angiotensin I / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antiviral Agents / therapeutic use
  • Betacoronavirus / drug effects
  • Betacoronavirus / pathogenicity*
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Coronavirus Infections / complications
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / genetics*
  • Gene Expression Regulation
  • Host-Pathogen Interactions / genetics
  • Humans
  • Pandemics*
  • Peptide Fragments / therapeutic use
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / genetics*
  • Prognosis
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • Sex Factors
  • Signal Transduction
  • Spike Glycoprotein, Coronavirus / genetics*
  • Spike Glycoprotein, Coronavirus / metabolism


  • Angiotensin-Converting Enzyme Inhibitors
  • Antiviral Agents
  • Peptide Fragments
  • Receptor, Angiotensin, Type 1
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2
  • angiotensin I (1-7)

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2