Preventing the development of severe COVID-19 by modifying immunothrombosis.

Gerwyn Morris, Chiara C Bortolasci, Basant K Puri, Lisa Olive, Wolfgang Marx, Adrienne O'Neil, Eugene Athan, Andre Carvalho, Michael Maes, Ken Walder, Michael Berk

Journal: Life sciences 2021;264():118617

PMID: 33096114

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Abstract

BACKGROUND

COVID-19-associated acute respiratory distress syndrome (ARDS) is associated with significant morbidity and high levels of mortality. This paper describes the processes involved in the pathophysiology of COVID-19 from the initial infection and subsequent destruction of type II alveolar epithelial cells by SARS-CoV-2 and culminating in the development of ARDS.

MAIN BODY

The activation of alveolar cells and alveolar macrophages leads to the release of large quantities of proinflammatory cytokines and chemokines and their translocation into the pulmonary vasculature. The presence of these inflammatory mediators in the vascular compartment leads to the activation of vascular endothelial cells platelets and neutrophils and the subsequent formation of platelet neutrophil complexes. These complexes in concert with activated endothelial cells interact to create a state of immunothrombosis. The consequence of immunothrombosis include hypercoagulation, accelerating inflammation, fibrin deposition, migration of neutrophil extracellular traps (NETs) producing neutrophils into the alveolar apace, activation of the NLRP3 inflammazome, increased alveolar macrophage destruction and massive tissue damage by pyroptosis and necroptosis Therapeutic combinations aimed at ameliorating immunothrombosis and preventing the development of severe COVID-19 are discussed in detail.

Address: Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Deakin University, Centre for Molecular and Medical Research, School of Medicine, Geelong, Australia.; C.A.R., Cambridge, UK.; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; School of Psychology, Deakin University, Geelong, Australia.; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Melbourne School of Population and Global Health, Melbourne, Australia.; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Barwon Health, Geelong, Australia.; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, University of Toronto, Toronto, Canada; Centre for Addiction and Mental Health (CAMH), Toronto, Canada.; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry, King Chulalongkorn University Hospital, Bangkok, Thailand; Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria.; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, The University of Melbourne, Melbourne, Australia. Electronic address: [email protected].

DOI: 10.1016/j.lfs.2020.118617

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MeSH Terms: Alveolar Epithelial Cells, Blood Platelets, COVID-19, Cytokines, Endothelial Cells, Humans, Macrophages, Alveolar, Neutrophils, Respiratory Distress Syndrome, SARS-CoV-2, Thrombosis, COVID-19 Drug Treatment