Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19

Hypertens Res. 2020 Jul;43(7):648-654. doi: 10.1038/s41440-020-0455-8. Epub 2020 Apr 27.

Abstract

The rapid spread of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19). Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV-2 to enter host target cells. Given that angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated ACE2 expression in animal studies, the concern might arise regarding whether ARBs and ACEIs would increase the morbidity and mortality of COVID-19. On the other hand, animal data suggested a potential protective effect of ARBs against COVID-19 pneumonia because an ARB prevented the aggravation of acute lung injury in mice infected with SARS-CoV, which is closely related to SARS-CoV-2. Importantly, however, there is no clinical or experimental evidence supporting that ARBs and ACEIs either augment the susceptibility to SARS-CoV-2 or aggravate the severity and outcomes of COVID-19 at present. Until further data are available, it is recommended that ARB and ACEI medications be continued for the treatment of patients with cardiovascular disease and hypertension, especially those at high risk, according to guideline-directed medical therapy based on the currently available evidence.

Keywords: Acute lung injury; Angiotensin II type-1 receptor; Angiotensin receptor blocker; Angiotensin-converting enzyme inhibitor; Severe acute respiratory syndrome coronavirus 2.

Publication types

  • Review

MeSH terms

  • Angiotensin II / physiology*
  • Angiotensin Receptor Antagonists / adverse effects*
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Animals
  • Betacoronavirus*
  • COVID-19
  • Coronavirus Infections / etiology*
  • Humans
  • Pandemics
  • Peptidyl-Dipeptidase A / physiology*
  • Pneumonia, Viral / etiology*
  • SARS-CoV-2

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin II
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2