The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19)
release_v32opha6j5hstc6ncet6ilzjzu
by
Pere Domingo, Isabel Mur, Virginia Pomar, Héctor Corominas, Jordi Casademont, Natividad de Benito
Abstract
The pathogenesis of coronavirus disease 2019 (COVID-19) may be envisaged as the dynamic interaction between four vicious feedback loops chained or happening at once. These are the viral loop, the hyperinflammatory loop, the non-canonical renin-angiotensin system (RAS) axis loop, and the hypercoagulation loop. Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1-7)/Mas1R axis. The viral feedback loop includes evading the host's innate response, uncontrolled viral replication, and turning on a hyperactive adaptative immune response. The inflammatory loop is composed of the exuberant inflammatory response feeding back until exploding in an actual cytokine storm. Downregulation of the ACE2/Ang-(1-7)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS. The coagulation loop is a hypercoagulable state caused by the interplay between inflammation and coagulation in an endless feedback loop. The result is a hyperinflammatory and hypercoagulable state producing acute immune-mediated lung injury and eventually, adult respiratory distress syndrome.
In text/plain
format
Archived Files and Locations
application/pdf 3.9 MB
file_7mbfrtup55bntfye7s7x3r4zw4
|
europepmc.org (repository) web.archive.org (webarchive) |
access all versions, variants, and formats of this works (eg, pre-prints)
Crossref Metadata (via API)
Worldcat
SHERPA/RoMEO (journal policies)
wikidata.org
CORE.ac.uk
Semantic Scholar
Google Scholar