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COVID‐19: A collision of complement, coagulation and inflammatory pathways

COVID‐19 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical acute respiratory distress syndrome (ARDS) seen in other severe pathogenic infections. Parallels with systemic inf...

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Detalles Bibliográficos
Autores principales: Chauhan, Anoop J., Wiffen, Laura J., Brown, Thomas P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. Journal of Thrombosis and Haemostasis published by ELSEVIER INC. on behalf of International Society on Thrombosis and Haemostasis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361520/
https://www.ncbi.nlm.nih.gov/pubmed/32608159
http://dx.doi.org/10.1111/jth.14981
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author Chauhan, Anoop J.
Wiffen, Laura J.
Brown, Thomas P.
author_facet Chauhan, Anoop J.
Wiffen, Laura J.
Brown, Thomas P.
author_sort Chauhan, Anoop J.
collection PubMed
description COVID‐19 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical acute respiratory distress syndrome (ARDS) seen in other severe pathogenic infections. Parallels with systemic inflammatory disorders such as atypical hemolytic uremic syndrome (aHUS) have implicated the complement pathway in the pathogenesis of COVID‐19, and particularly the anaphylatoxins C3a and C5a released from cleavage of C3 and C5, respectively. C5a is a potent cell signalling protein that activates a cytokine storm—a hyper‐inflammatory phenomenon—within hours of infection and the innate immune response. However, excess C5a can result in a pro‐inflammatory environment orchestrated through a plethora of mechanisms that propagate lung injury, lymphocyte exhaustion, and an immune paresis. Furthermore, disruption of the homeostatic interactions between complement and extrinsic and intrinsic coagulation pathways contributes to a net pro‐coagulant state in the microvasculature of critical organs. Fatal COVID‐19 has been associated with a systemic inflammatory response accompanied by a pro‐coagulant state and organ damage, particularly microvascular thrombi in the lungs and kidneys. Pathologic studies report strong evidence of complement activation. C5 blockade reduces inflammatory cytokines and their manifestations in animal studies, and has shown benefits in patients with aHUS, prompting investigation of this approach in the treatment of COVID‐19. This review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID‐19.
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spelling pubmed-73615202020-07-15 COVID‐19: A collision of complement, coagulation and inflammatory pathways Chauhan, Anoop J. Wiffen, Laura J. Brown, Thomas P. J Thromb Haemost Review Article COVID‐19 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical acute respiratory distress syndrome (ARDS) seen in other severe pathogenic infections. Parallels with systemic inflammatory disorders such as atypical hemolytic uremic syndrome (aHUS) have implicated the complement pathway in the pathogenesis of COVID‐19, and particularly the anaphylatoxins C3a and C5a released from cleavage of C3 and C5, respectively. C5a is a potent cell signalling protein that activates a cytokine storm—a hyper‐inflammatory phenomenon—within hours of infection and the innate immune response. However, excess C5a can result in a pro‐inflammatory environment orchestrated through a plethora of mechanisms that propagate lung injury, lymphocyte exhaustion, and an immune paresis. Furthermore, disruption of the homeostatic interactions between complement and extrinsic and intrinsic coagulation pathways contributes to a net pro‐coagulant state in the microvasculature of critical organs. Fatal COVID‐19 has been associated with a systemic inflammatory response accompanied by a pro‐coagulant state and organ damage, particularly microvascular thrombi in the lungs and kidneys. Pathologic studies report strong evidence of complement activation. C5 blockade reduces inflammatory cytokines and their manifestations in animal studies, and has shown benefits in patients with aHUS, prompting investigation of this approach in the treatment of COVID‐19. This review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID‐19. The Authors. Journal of Thrombosis and Haemostasis published by ELSEVIER INC. on behalf of International Society on Thrombosis and Haemostasis 2020-09 2022-12-21 /pmc/articles/PMC7361520/ /pubmed/32608159 http://dx.doi.org/10.1111/jth.14981 Text en © 2020 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Review Article
Chauhan, Anoop J.
Wiffen, Laura J.
Brown, Thomas P.
COVID‐19: A collision of complement, coagulation and inflammatory pathways
title COVID‐19: A collision of complement, coagulation and inflammatory pathways
title_full COVID‐19: A collision of complement, coagulation and inflammatory pathways
title_fullStr COVID‐19: A collision of complement, coagulation and inflammatory pathways
title_full_unstemmed COVID‐19: A collision of complement, coagulation and inflammatory pathways
title_short COVID‐19: A collision of complement, coagulation and inflammatory pathways
title_sort covid‐19: a collision of complement, coagulation and inflammatory pathways
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361520/
https://www.ncbi.nlm.nih.gov/pubmed/32608159
http://dx.doi.org/10.1111/jth.14981
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