1. COVID-19 cytokine storm: The anger of inflammation.
- Author
-
Mahmudpour M, Roozbeh J, Keshavarz M, Farrokhi S, and Nabipour I
- Subjects
- Angiotensin-Converting Enzyme 2, Betacoronavirus pathogenicity, Bradykinin metabolism, COVID-19, Complement C5a immunology, Complement C5a metabolism, Complement C5b immunology, Complement C5b metabolism, Coronavirus Infections enzymology, Humans, Inflammation enzymology, Inflammation immunology, Models, Molecular, Pandemics, Pneumonia, Viral enzymology, Proto-Oncogene Mas, Proto-Oncogene Proteins metabolism, Receptors, G-Protein-Coupled metabolism, Renin-Angiotensin System immunology, SARS-CoV-2, Betacoronavirus metabolism, Coronavirus Infections immunology, Coronavirus Infections metabolism, Cytokines metabolism, Inflammation metabolism, Peptidyl-Dipeptidase A metabolism, Pneumonia, Viral immunology, Pneumonia, Viral metabolism, Spike Glycoprotein, Coronavirus metabolism
- Abstract
Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: An award was given to Iraj Nabipour by “Novo Nordisk Pars” (The Best Innovator of Diabetes in Iran 2013). For the remaining authors none were declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF