A hypothesized role for dysregulated bradykinin signaling in COVID-19 respiratory complications

FASEB J. 2020 Jun;34(6):7265-7269. doi: 10.1096/fj.202000967. Epub 2020 May 2.

Abstract

As of April 20, 2020, over time, the COVID-19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative that safe and effective pharmacotherapeutic strategies are rapidly explored to improve survival. In this paper, we use established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop of des-Arg(9)-bradykinin- and bradykinin-mediated inflammation → injury → inflammation, likely precipitates life threatening respiratory complications in COVID-19. Through our hypothesis, we make the prediction that the FDA-approved molecule, icatibant, might be able to interrupt this feedback loop and, thereby, improve the clinical outcomes. This hypothesis could lead to basic, translational, and clinical studies aimed at reducing COVID-19 morbidity and mortality.

Keywords: bradykinin; bradykinin receptor; coronavirus; icatibant; inflammation; injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus*
  • Bradykinin / analogs & derivatives*
  • Bradykinin / pharmacology
  • Bradykinin / physiology
  • Bradykinin / therapeutic use
  • Bradykinin B2 Receptor Antagonists / pharmacology
  • Bradykinin B2 Receptor Antagonists / therapeutic use*
  • COVID-19
  • COVID-19 Drug Treatment
  • Compassionate Use Trials
  • Coronavirus Infections / complications
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / physiopathology*
  • Dyspnea / etiology
  • Dyspnea / physiopathology
  • Feedback, Physiological / drug effects
  • Humans
  • Inflammation
  • Models, Biological*
  • Off-Label Use
  • Pandemics
  • Peptidyl-Dipeptidase A / physiology*
  • Pneumonia, Viral / complications
  • Pneumonia, Viral / drug therapy
  • Pneumonia, Viral / physiopathology*
  • Receptors, Bradykinin / drug effects
  • Receptors, Bradykinin / physiology
  • Receptors, Virus / physiology*
  • SARS-CoV-2

Substances

  • Bradykinin B2 Receptor Antagonists
  • Receptors, Bradykinin
  • Receptors, Virus
  • bradykinin, des-Arg(9)-
  • icatibant
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Bradykinin