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COVID-19: A collision of complement, coagulation and inflammatory pathways.
Chauhan, Anoop J; Wiffen, Laura J; Brown, Thomas P.
  • Chauhan AJ; Research and Innovation, Queen Alexandra Hospital, Portsmouth, UK.
  • Wiffen LJ; Faculty of Science and Health, University of Portsmouth, Portsmouth, UK.
  • Brown TP; Respiratory Medicine, Queen Alexandra Hospital, Portsmouth, UK.
J Thromb Haemost ; 18(9): 2110-2117, 2020 09.
Article in English | MEDLINE | ID: covidwho-623519
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Blood Coagulation / Complement C3a / Complement C5a / Complement Activation / COVID-19 / Inflammation Topics: Long Covid Limits: Animals / Humans Language: English Journal: J Thromb Haemost Journal subject: Hematology Year: 2020 Document Type: Article Affiliation country: Jth.14981

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Blood Coagulation / Complement C3a / Complement C5a / Complement Activation / COVID-19 / Inflammation Topics: Long Covid Limits: Animals / Humans Language: English Journal: J Thromb Haemost Journal subject: Hematology Year: 2020 Document Type: Article Affiliation country: Jth.14981