Beta-Adrenergic Blockers as a Potential Treatment for COVID-19 Patients

Bioessays. 2020 Nov;42(11):e2000094. doi: 10.1002/bies.202000094. Epub 2020 Sep 2.

Abstract

More than 15 million people have been affected by coronavirus disease 2019 (COVID-19) and it has caused 640 016 deaths as of July 26, 2020. Currently, no effective treatment option is available for COVID-19 patients. Though many drugs have been proposed, none of them has shown particular efficacy in clinical trials. In this article, the relationship between the Adrenergic system and the renin-angiotensin-aldosterone system (RAAS) is focused in COVID-19 and a vicious circle consisting of the Adrenergic system-RAAS-Angiotensin converting enzyme 2 (ACE2)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (which is referred to as the "ARAS loop") is proposed. Hyperactivation of the ARAS loop may be the underlying pathophysiological mechanism in COVID-19, and beta-adrenergic blockers are proposed as a potential treatment option. Beta-adrenergic blockers may decrease the SARS-CoV-2 cellular entry by decreasing ACE2 receptors expression and cluster of differentiation 147 (CD147) in various cells in the body. Beta-adrenergic blockers may decrease the morbidity and mortality in COVID-19 patients by preventing or reducing acute respiratory distress syndrome (ARDS) and other complications. Retrospective and prospective clinical trials should be conducted to check the validity of the hypothesis. Also see the video abstract here https://youtu.be/uLoy7do5ROo.

Keywords: ACE2; ARDS; COVID-19; SARS-CoV-2; beta-adrenergic blockers; pulmonary embolism; septic shock.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / drug effects
  • Betacoronavirus / physiology
  • COVID-19
  • Carvedilol / pharmacology
  • Carvedilol / therapeutic use
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology
  • Coronavirus Papain-Like Proteases
  • Drug Repositioning / methods
  • Humans
  • Inflammasomes / drug effects
  • Inflammasomes / metabolism
  • Inflammation Mediators / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Pandemics
  • Papain / antagonists & inhibitors
  • Papain / metabolism
  • Peptidyl-Dipeptidase A / drug effects
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology
  • Protease Inhibitors / pharmacology
  • Protease Inhibitors / therapeutic use
  • Pulmonary Embolism / prevention & control
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • Respiratory Insufficiency / prevention & control
  • SARS-CoV-2
  • Shock, Septic / prevention & control
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / metabolism
  • Virus Internalization / drug effects

Substances

  • Adrenergic beta-Antagonists
  • Inflammasomes
  • Inflammation Mediators
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Protease Inhibitors
  • Viral Nonstructural Proteins
  • Carvedilol
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Coronavirus Papain-Like Proteases
  • Papain
  • papain-like protease, SARS-CoV-2