Inflammation and thrombosis in COVID-19 pathophysiology: proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets.

Physiological Reviews
Krishna Sriram, Paul A Insel

Abstract

Evolving information has identified disease mechanisms and dysregulation of host biology that might be targeted therapeutically in coronavirus disease 2019 (COVID-19). Thrombosis and coagulopathy, associated with pulmonary injury and inflammation, are emerging clinical features of COVID-19. We present a framework for mechanisms of thrombosis in COVID-19 that initially derive from interaction of SARS-CoV-2 with ACE2, resulting in dysregulation of angiotensin signaling and subsequent inflammation and tissue injury. These responses result in increased signaling by thrombin (proteinase-activated) and purinergic receptors, which promote platelet activation and exert pathological effects on other cell types (e.g., endothelial cells, epithelial cells, and fibroblasts), further enhancing inflammation and injury. Inhibitors of thrombin and purinergic receptors may, thus, have therapeutic effects by blunting platelet-mediated thromboinflammation and dysfunction in other cell types. Such inhibitors include agents (e.g., anti-platelet drugs) approved for other indications, and that could be repurposed to treat, and potentially improve the outcome of, COVID-19 patients. COVID-19, caused by the SARS-CoV-2 virus, drives dysregulation of angio...Continue Reading

References

Jun 6, 1995·Biochemical and Biophysical Research Communications·C UneyamaM Takahashi
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·R MöhleS Rafii
Jun 20, 2001·The Journal of Clinical Investigation·D WoulfeL Brass
Mar 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nithiananthan AsokananthanGeoffrey A Stewart
Jul 10, 2003·JAMA : the Journal of the American Medical Association·Edward AbrahamUNKNOWN OPTIMIST Trial Study Group
May 1, 2004·Critical Care Medicine·Jean-François DhainautYann-Erick Claessens
Feb 15, 2005·Experimental Cell Research·Olivier P Blanc-BrudeRachel C Chambers
Apr 20, 2005·The Journal of Infectious Diseases·W K Eddie IpYu Lung Lau
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·J I Weitz, S M Bates
Feb 24, 2006·Blood·Samir K MandalL Vijaya Mohan Rao
Jun 23, 2007·Circulation Research·Zaverio M Ruggeri, G Loredana Mendolicchio
May 16, 2008·Haemophilia : the Official Journal of the World Federation of Hemophilia·M K ten Kate, J van der Meer
Jun 4, 2008·Thrombosis and Haemostasis·Marie-Christine Alessi, Irène Juhan-Vague
Aug 30, 2008·American Journal of Respiratory Cell and Molecular Biology·Fernando A BozzaGuy A Zimmerman
Nov 26, 2008·Advances in Experimental Medicine and Biology·Umme AmaraMarkus Huber-Lang
Jan 9, 2009·Mucosal Immunology·M S Wilson, T A Wynn
Apr 18, 2009·Blood·Paola E J van der MeijdenJohan W M Heemskerk
Jan 1, 2010·American Journal of Physiology. Cell Physiology·José P YoungAdam Myers
Jul 14, 2010·Molecular Immunology·Ellinor I PeerschkeBerhane Ghebrehiwet
Sep 28, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Umme AmaraMarkus Huber-Lang
Feb 26, 2011·Blood·Michael R Blackburn
Mar 26, 2011·Nature Reviews. Immunology·John W SempleJohn Freedman
Jul 19, 2011·Immunology Letters·Fleur BossiFrancesco Tedesco
Aug 4, 2011·Seminars in Immunopathology·Katerina OikonomopoulouJohn D Lambris
Aug 19, 2011·Immunologic Research·Cosmin A TeglaHorea Rus
Mar 27, 2012·The New England Journal of Medicine·David A MorrowUNKNOWN TRA 2P–TIMI 50 Steering Committee and Investigators
Apr 6, 2012·International Journal of Hematology·James H Morrissey
May 24, 2012·The New England Journal of Medicine·V Marco RanieriUNKNOWN PROWESS-SHOCK Study Group
Oct 3, 2012·Thrombosis Research·Katrin Faye Nickel, Thomas Renné
Dec 14, 2012·The New England Journal of Medicine·Holger K EltzschigSimon C Robson
Apr 23, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Fiona A MartinPhilip M Cummins
Nov 5, 2013·Thorax·Ricardo J JoséRachel C Chambers
Dec 25, 2013·Blood·Kimberly Martinod, Denisa D Wagner
Jan 28, 2014·Haematologica·Christian Andrea Di BuduoAlessandra Balduini
Feb 7, 2014·British Journal of Haematology·Ian S Hitchcock, Kenneth Kaushansky

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Citations

Jan 30, 2021·Trends in Biotechnology·Yuqi ZhouKeisuke Goda
Apr 1, 2021·Physiological Reviews·Alberto L HorensteinFabio Malavasi
Jun 8, 2021·Clinical and Translational Gastroenterology·David H Alpers
Mar 11, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Vitalii Kryvenko, István Vadász

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Methods Mentioned

BETA
RNA-seq
transgenic

Clinical Trials Mentioned

NCT04366050
NCT04335123
NCT04312009
NCT04335136
NCT04332666
NCT04409834
NCT04333407
NCT04351724
NCT04324463
NCT04394377

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