Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System? A Call for Epidemiologic Investigations

Clin Infect Dis. 2020 Jul 28;71(15):870-874. doi: 10.1093/cid/ciaa329.

Abstract

Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.

Keywords: COVID-19; SARS-CoV-2; angiotensin-converting enzyme 2; cardiovascular disease; renin-angiotensin system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / pathogenicity
  • COVID-19
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / virology
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / metabolism*
  • Coronavirus Infections / mortality*
  • Coronavirus Infections / virology
  • Humans
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / metabolism*
  • Pneumonia, Viral / mortality*
  • Pneumonia, Viral / virology
  • Renin-Angiotensin System / physiology*
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome / epidemiology
  • Severe Acute Respiratory Syndrome / metabolism*
  • Severe Acute Respiratory Syndrome / mortality*
  • Severe Acute Respiratory Syndrome / virology

Substances

  • Angiotensin II
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2