A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes’ interactions points to Neutrophil Extracellular Traps as mediators of thrombosis in COVID-19
A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes’ interactions points to Neutrophil Extracellular Traps as mediators of thrombosis in COVID-19
Abstract Abnormal coagulation and an increased risk of thrombosis are features of severe COVID-19, with parallels proposed with hemophagocytic lymphohistiocytosis (HLH), a life-threating condition associated with hyperinflammation. The presence of HLH was described in severely ill patients during the H1N1 influenza epidemic, presenting with pulmonary vascular thrombosis. We tested the hypothesis that genes causing primary HLH regulate pathways linking pulmonary thromboembolism to the presence of SARS-CoV-2 using novel network-informed computational algorithms. This approach led to the identification of Neutrophils Extracellular Traps (NETs) as plausible mediators of vascular thrombosis in severe COVID-19 in children and adults. Taken together, the network-informed analysis led us to propose the following model: the release of NETs in response to inflammatory signals acting in concert with SARS-CoV-2 damage the endothelium and direct platelet-activation promoting abnormal coagulation leading to serious complications of COVID-19. The underlying hypothesis is that genetic and/or environmental conditions that favor the release of NETs may predispose individuals to thrombotic complications of COVID-19 due to an increase risk of abnormal coagulation. This would be a common pathogenic mechanism in conditions including autoimmune/infectious diseases, hematologic and metabolic disorders.
Rousseau Simon、Tremblay Karine、Millette Simon、El Khili Mohamed Reda、Noorah Nuzha、Spicer Jonathan、Fonseca Gregory、Sirois Martin、Ding Jun、Hostallero David Earl、Emad Amin、Daneshtalab Noriko、Guay-Belzile Myriam
The Meakins-Christie Laboratories at the Research Institute of the McGill University Heath Centre Research InstitutePharmacology-physiology Department, Faculty of Medicine and Health Sciences, Universit¨| de Sherbrooke, Centre int¨|gr¨| universitaire de sant¨| et de services sociaux du Saguenay¨CLac-Saint-Jean (Chicoutimi University Hospital) Research CenterGoodman Cancer Research Centre, McGill UniversityDepartment of Electrical and Computer Engineering, McGill UniversityThe Meakins-Christie Laboratories at the Research Institute of the McGill University Heath Centre Research InstituteDivision of Thoracic and Upper Gastrointestinal Surgery, McGill University Health Centre Research InstituteThe Meakins-Christie Laboratories at the Research Institute of the McGill University Heath Centre Research InstituteMontreal Heart Institute and Department of pharmacology and physiology, Faculty of medicine, Universit¨| de Montr¨|alComputational Biology Department, Carnegie Mellon UniversityDepartment of Electrical and Computer Engineering, McGill UniversityDepartment of Electrical and Computer Engineering, McGill UniversitySchool of Pharmacy, Memorial University of Newfoundland, 300 Prince Philip Drive, Health Sciences CenterThe Meakins-Christie Laboratories at the Research Institute of the McGill University Heath Centre Research Institute
医药卫生理论医学研究方法基础医学
Rousseau Simon,Tremblay Karine,Millette Simon,El Khili Mohamed Reda,Noorah Nuzha,Spicer Jonathan,Fonseca Gregory,Sirois Martin,Ding Jun,Hostallero David Earl,Emad Amin,Daneshtalab Noriko,Guay-Belzile Myriam.A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes’ interactions points to Neutrophil Extracellular Traps as mediators of thrombosis in COVID-19[EB/OL].(2025-03-28)[2025-05-12].https://www.medrxiv.org/content/10.1101/2020.07.01.20144121.点此复制
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