Clinical Implications of SARS-CoV-2 Interaction With Renin Angiotensin System: JACC Review Topic of the Week

J Am Coll Cardiol. 2020 Jun 23;75(24):3085-3095. doi: 10.1016/j.jacc.2020.04.028. Epub 2020 Apr 16.


Severe acute respiratory-syndrome coronavirus-2 (SARS-CoV-2) host cell infection is mediated by binding to angiotensin-converting enzyme 2 (ACE2). Systemic dysregulation observed in SARS-CoV was previously postulated to be due to ACE2/angiotensin 1-7 (Ang1-7)/Mas axis downregulation; increased ACE2 activity was shown to mediate disease protection. Because angiotensin II receptor blockers, ACE inhibitors, and mineralocorticoid receptor antagonists increase ACE2 receptor expression, it has been tacitly believed that the use of these agents may facilitate viral disease; thus, they should not be used in high-risk patients with cardiovascular disease. Based on the anti-inflammatory benefits of the upregulation of the ACE2/Ang1-7/Mas axis and previously demonstrated benefits of lung function improvement in SARS-CoV infections, it has been hypothesized that the benefits of treatment with renin-angiotensin system inhibitors in SARS-CoV-2 may outweigh the risks and at the very least should not be withheld.

Keywords: ACE inhibitor; COVID-19; SARS-CoV-2; angiotensin II receptor blockers; angiotensin-converting enzyme-2; mineralocorticoid receptor antagonist.

Publication types

  • Review

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology*
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Betacoronavirus* / drug effects
  • Betacoronavirus* / physiology
  • COVID-19
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / metabolism
  • Coronavirus Infections* / physiopathology
  • Coronavirus Infections* / therapy
  • Coronavirus Infections* / virology
  • Host Microbial Interactions / drug effects
  • Humans
  • Medication Therapy Management
  • Mineralocorticoid Receptor Antagonists / pharmacology*
  • Pandemics*
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral* / physiopathology
  • Pneumonia, Viral* / therapy
  • Pneumonia, Viral* / virology
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • SARS-CoV-2


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Mineralocorticoid Receptor Antagonists
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2