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Rationale for targeting complement in COVID-19.
EMBO Mol Med. 2020 Aug 07; 12(8):e12642.EM

Abstract

A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life-threatening acute respiratory distress syndrome (ARDS). The complement system is part of the innate immune arsenal against pathogens, in which many viruses can evade or employ to mediate cell entry. The immunopathology and acute lung injury orchestrated through the influx of pro-inflammatory macrophages and neutrophils can be directly activated by complement components to prime an overzealous cytokine storm. The manifestations of severe COVID-19 such as the ARDS, sepsis and multiorgan failure have an established relationship with activation of the complement cascade. We have collected evidence from all the current studies we are aware of on SARS-CoV-2 immunopathogenesis and the preceding literature on SARS-CoV-1 and MERS-CoV infection linking severe COVID-19 disease directly with dysfunction of the complement pathways. This information lends support for a therapeutic anti-inflammatory strategy against complement, where a number of clinically ready potential therapeutic agents are available.

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Authors+Show Affiliations

Polycarpou A
MRC Centre of Transplantation, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Guy's Hospital, King's College London, London, UK.
Howard M
MRC Centre of Transplantation, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Guy's Hospital, King's College London, London, UK.
Farrar CA
MRC Centre of Transplantation, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Guy's Hospital, King's College London, London, UK.
Greenlaw R
MRC Centre of Transplantation, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Guy's Hospital, King's College London, London, UK.
Fanelli G
MRC Centre of Transplantation, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Guy's Hospital, King's College London, London, UK.
Wallis R
Department of Respiratory Science and Infection, Leicester Institute of Chemical and Structural Biology, University of Leicester, Leicester, UK.
Klavinskis LS
Department of Infectious Diseases, School of Immunology and Microbial Sciences, Guy's Hospital, King's College London, London, UK.
Sacks S
MRC Centre of Transplantation, Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Guy's Hospital, King's College London, London, UK.

MeSH

AdultAlveolar Epithelial CellsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCOVID-19ChildComplement ActivationComplement C3bComplement Inactivating AgentsCoronavirus InfectionsCytokine Release SyndromeGlycosylationHumansImmunity, InnateLigandsMiceModels, AnimalModels, MolecularPandemicsPattern Recognition, AutomatedPeptidyl-Dipeptidase APneumonia, ViralProtein ConformationProtein Processing, Post-TranslationalReceptors, VirusRespiratory Distress SyndromeSARS-CoV-2Spike Glycoprotein, CoronavirusCOVID-19 Drug Treatment

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32559343

Citation

Polycarpou, Anastasia, et al. "Rationale for Targeting Complement in COVID-19." EMBO Molecular Medicine, vol. 12, no. 8, 2020, pp. e12642.
Polycarpou A, Howard M, Farrar CA, et al. Rationale for targeting complement in COVID-19. EMBO Mol Med. 2020;12(8):e12642.
Polycarpou, A., Howard, M., Farrar, C. A., Greenlaw, R., Fanelli, G., Wallis, R., Klavinskis, L. S., & Sacks, S. (2020). Rationale for targeting complement in COVID-19. EMBO Molecular Medicine, 12(8), e12642. https://doi.org/10.15252/emmm.202012642
Polycarpou A, et al. Rationale for Targeting Complement in COVID-19. EMBO Mol Med. 2020 Aug 7;12(8):e12642. PubMed PMID: 32559343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rationale for targeting complement in COVID-19. AU - Polycarpou,Anastasia, AU - Howard,Mark, AU - Farrar,Conrad A, AU - Greenlaw,Roseanna, AU - Fanelli,Giorgia, AU - Wallis,Russell, AU - Klavinskis,Linda S, AU - Sacks,Steven, Y1 - 2020/07/12/ PY - 2020/4/30/received PY - 2020/5/28/revised PY - 2020/6/16/accepted PY - 2020/6/20/pubmed PY - 2020/8/22/medline PY - 2020/6/20/entrez KW - COVID-19 KW - SARS-CoV-2 KW - complement proteins KW - lectin pathway KW - therapeutics SP - e12642 EP - e12642 JF - EMBO molecular medicine JO - EMBO Mol Med VL - 12 IS - 8 N2 - A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life-threatening acute respiratory distress syndrome (ARDS). The complement system is part of the innate immune arsenal against pathogens, in which many viruses can evade or employ to mediate cell entry. The immunopathology and acute lung injury orchestrated through the influx of pro-inflammatory macrophages and neutrophils can be directly activated by complement components to prime an overzealous cytokine storm. The manifestations of severe COVID-19 such as the ARDS, sepsis and multiorgan failure have an established relationship with activation of the complement cascade. We have collected evidence from all the current studies we are aware of on SARS-CoV-2 immunopathogenesis and the preceding literature on SARS-CoV-1 and MERS-CoV infection linking severe COVID-19 disease directly with dysfunction of the complement pathways. This information lends support for a therapeutic anti-inflammatory strategy against complement, where a number of clinically ready potential therapeutic agents are available. SN - 1757-4684 UR - https://www.unboundmedicine.com/medline/citation/32559343/Rationale_for_targeting_complement_in_COVID_19_ DB - PRIME DP - Unbound Medicine ER -