The complement system in COVID-19: friend and foe?
Anuja Java,Anthony J. Apicelli,M. Kathryn Liszewski,Ariella Coler-Reilly,John P. Atkinson,Alfred H.J. Kim,Hrishikesh S. Kulkarni +6 more
TLDR
It is proposed that the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19 and create a basis for clinical trials of complement inhibitors in life-threatening illness.Abstract:
Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19-related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19; (d) a subset of patients with COVID-19 may have a genetic predisposition associated with complement dysregulation; and (e) these observations create a basis for clinical trials of complement inhibitors in life-threatening illness.read more
Citations
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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
Fei Zhou,Ting Yu,Ronghui Du,Guohui Fan,Ying Liu,Zhibo Liu,Jie Xiang,Yeming Wang,Bin Song,Xiaoying Gu,Xiaoying Gu,Lulu Guan,Yuan Wei,Li Hui,Xudong Wu,Jiuyang Xu,Shengjin Tu,Yi Zhang,Hua Chen,Bin Cao +19 more
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Journal ArticleDOI
Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis.
Panagiotis Skendros,Alexandros Mitsios,Akrivi Chrysanthopoulou,Dimitrios C. Mastellos,Simeon Metallidis,Petros I. Rafailidis,Maria Ntinopoulou,Eleni Sertaridou,Victoria Tsironidou,Christina Tsigalou,Maria G Tektonidou,Theocharis Konstantinidis,Charalampos Papagoras,Ioannis Mitroulis,Georgios Germanidis,John D. Lambris,Konstantinos Ritis +16 more
TL;DR: A mechanistic basis is provided for a pivotal role of complement and NETs in COVID-19 immunothrombosis and supports strategies against SARS-CoV-2 that exploit complement or NETosis inhibition.
Journal ArticleDOI
Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19.
Aldo Bonaventura,Aldo Bonaventura,Alessandra Vecchié,Lorenzo Dagna,Kimberly Martinod,Dave L. Dixon,Benjamin W. Van Tassell,Francesco Dentali,Fabrizio Montecucco,Steffen Massberg,Marcel Levi,Antonio Abbate +11 more
TL;DR: In this paper, the authors proposed that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels.
Journal ArticleDOI
Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation.
Sean X. Gu,Tarun Tyagi,Kanika Jain,Vivian W. Gu,Seung-Hee Lee,Jonathan M. Hwa,Jennifer M. Kwan,Diane S. Krause,Alfred Ian Lee,Stephanie Halene,Kathleen A. Martin,Hyung J. Chun,John Hwa +12 more
TL;DR: The latest evidence indicating that platelet and endothelial dysfunction are essential components of CO VID-19 pathology is summarized, the potential mechanisms underlying the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19 are described and the roles of coagulopathy, thrombocytopathy and endotheliopathy are highlighted.
Journal ArticleDOI
Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition.
TL;DR: It is demonstrated that the SARS-CoV-2 spike protein (subunit 1 and 2), but not the N protein, directly activates the alternative pathway of complement (APC), which may explain many of the clinical manifestations of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome.
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