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Is the COVID-19 thrombotic catastrophe complement-connected?
J Thromb Haemost. 2020 Aug 06 [Online ahead of print]JT

Abstract

In December 2019, the world was introduced to a new betacoronavirus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for its propensity to cause rapidly progressive lung damage, resulting in high death rates. As fast as the virus spread, it became evident that the novel coronavirus causes a multisystem disease (COVID-19) that may involve multiple organs and has a high risk of thrombosis associated with striking elevations in pro-inflammatory cytokines, D-dimer, and fibrinogen, but without disseminated intravascular coagulation. Postmortem studies have confirmed the high incidence of venous thromboembolism, but also notably revealed diffuse microvascular thrombi with endothelial swelling, consistent with a thrombotic microangiopathy, and inter-alveolar endothelial deposits of complement activation fragments. The clinicopathologic presentation of COVID-19 thus parallels that of other thrombotic diseases, such as atypical hemolytic uremic syndrome (aHUS), that are caused by dysregulation of the complement system. This raises the specter that many of the thrombotic complications arising from SARS-CoV-2 infections may be triggered and/or exacerbated by excess complement activation. This is of major potential clinical relevance, as currently available anti-complement therapies that are highly effective in protecting against thrombosis in aHUS, could be efficacious in COVID-19. In this review, we provide mounting evidence for complement participating in the pathophysiology underlying the thrombotic diathesis associated with pathogenic coronaviruses, including SARS-CoV-2. Based on current knowledge of complement, coagulation and the virus, we suggest lines of study to identify novel therapeutic targets and the rationale for clinical trials with currently available anti-complement agents for COVID-19.

Authors+Show Affiliations

Centre for Blood Research, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.Centre for Blood Research, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. Canadian Blood Services, Centre for Innovation, University of British Columbia, Vancouver, British Columbia, Canada. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32762081

Citation

Conway, Edward M., and Edward L G. Pryzdial. "Is the COVID-19 Thrombotic Catastrophe Complement-connected?" Journal of Thrombosis and Haemostasis : JTH, 2020.
Conway EM, Pryzdial ELG. Is the COVID-19 thrombotic catastrophe complement-connected? J Thromb Haemost. 2020.
Conway, E. M., & Pryzdial, E. L. G. (2020). Is the COVID-19 thrombotic catastrophe complement-connected? Journal of Thrombosis and Haemostasis : JTH. https://doi.org/10.1111/jth.15050
Conway EM, Pryzdial ELG. Is the COVID-19 Thrombotic Catastrophe Complement-connected. J Thromb Haemost. 2020 Aug 6; PubMed PMID: 32762081.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Is the COVID-19 thrombotic catastrophe complement-connected? AU - Conway,Edward M, AU - Pryzdial,Edward L G, Y1 - 2020/08/06/ PY - 2020/06/01/received PY - 2020/07/15/revised PY - 2020/07/31/accepted PY - 2020/8/8/pubmed PY - 2020/8/8/medline PY - 2020/8/8/entrez KW - complement KW - covid-19 KW - microvascular KW - thrombotic microangiopathy KW - tissue factor JF - Journal of thrombosis and haemostasis : JTH JO - J. Thromb. Haemost. N2 - In December 2019, the world was introduced to a new betacoronavirus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for its propensity to cause rapidly progressive lung damage, resulting in high death rates. As fast as the virus spread, it became evident that the novel coronavirus causes a multisystem disease (COVID-19) that may involve multiple organs and has a high risk of thrombosis associated with striking elevations in pro-inflammatory cytokines, D-dimer, and fibrinogen, but without disseminated intravascular coagulation. Postmortem studies have confirmed the high incidence of venous thromboembolism, but also notably revealed diffuse microvascular thrombi with endothelial swelling, consistent with a thrombotic microangiopathy, and inter-alveolar endothelial deposits of complement activation fragments. The clinicopathologic presentation of COVID-19 thus parallels that of other thrombotic diseases, such as atypical hemolytic uremic syndrome (aHUS), that are caused by dysregulation of the complement system. This raises the specter that many of the thrombotic complications arising from SARS-CoV-2 infections may be triggered and/or exacerbated by excess complement activation. This is of major potential clinical relevance, as currently available anti-complement therapies that are highly effective in protecting against thrombosis in aHUS, could be efficacious in COVID-19. In this review, we provide mounting evidence for complement participating in the pathophysiology underlying the thrombotic diathesis associated with pathogenic coronaviruses, including SARS-CoV-2. Based on current knowledge of complement, coagulation and the virus, we suggest lines of study to identify novel therapeutic targets and the rationale for clinical trials with currently available anti-complement agents for COVID-19. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/32762081/Is_the_COVID-19_thrombotic_catastrophe_complement-connected L2 - https://doi.org/10.1111/jth.15050 DB - PRIME DP - Unbound Medicine ER -
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