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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.
Ding, Jun; Hostallero, David Earl; El Khili, Mohamed Reda; Fonseca, Gregory Joseph; Milette, Simon; Noorah, Nuzha; Guay-Belzile, Myriam; Spicer, Jonathan; Daneshtalab, Noriko; Sirois, Martin; Tremblay, Karine; Emad, Amin; Rousseau, Simon.
  • Ding J; Computational Biology Department, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.
  • Hostallero DE; The Meakins-Christie Laboratories at the Research Institute of the McGill University Heath Centre Research Institute, Montréal, Canada.
  • El Khili MR; Department of Electrical and Computer Engineering, McGill University, Montréal, Canada.
  • Fonseca GJ; Department of Electrical and Computer Engineering, McGill University, Montréal, Canada.
  • Milette S; The Meakins-Christie Laboratories at the Research Institute of the McGill University Heath Centre Research Institute, Montréal, Canada.
  • Noorah N; Goodman Cancer Research Centre, McGill University, Montréal, Canada.
  • Guay-Belzile M; The Meakins-Christie Laboratories at the Research Institute of the McGill University Heath Centre Research Institute, Montréal, Canada.
  • Spicer J; The Meakins-Christie Laboratories at the Research Institute of the McGill University Heath Centre Research Institute, Montréal, Canada.
  • Daneshtalab N; Division of Thoracic and Upper Gastrointestinal Surgery, McGill University Health Centre Research Institute, Montréal, Canada.
  • Sirois M; School of Pharmacy, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
  • Tremblay K; Montreal Heart Institute and Department of pharmacology and physiology, Faculty of medicine, Université de Montréal, Montréal, Canada.
  • Emad A; Pharmacology-physiology Department, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean (Chicoutimi University Hospital) Research Center, Saguenay, Canada.
  • Rousseau S; Department of Electrical and Computer Engineering, McGill University, Montréal, Canada.
PLoS Comput Biol ; 17(3): e1008810, 2021 03.
Article in English | MEDLINE | ID: covidwho-1121603
Preprint
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Semantic information from SemMedBD (by NLM)
1. Thrombosis COEXISTS_WITH COVID-19
Subject
Thrombosis
Predicate
COEXISTS_WITH
Object
COVID-19
2. Malaise PROCESS_OF Patients
Subject
Malaise
Predicate
PROCESS_OF
Object
Patients
3. Lymphohistiocytosi PROCESS_OF C0030705
Subject
Lymphohistiocytosi
Predicate
PROCESS_OF
Object
C0030705
4. Present COEXISTS_WITH Influenza
Subject
Present
Predicate
COEXISTS_WITH
Object
Influenza
5. Present COEXISTS_WITH Pulmonary thrombosis
Subject
Present
Predicate
COEXISTS_WITH
Object
Pulmonary thrombosis
6. Genes CAUSES Familial Hemophagocytic Lymphocytosis
Subject
Genes
Predicate
CAUSES
Object
Familial Hemophagocytic Lymphocytosis
7. Pulmonary Thromboembolisms COEXISTS_WITH 2019 novel coronavirus
Subject
Pulmonary Thromboembolisms
Predicate
COEXISTS_WITH
Object
2019 novel coronavirus
8. Thrombosis of blood vessel COEXISTS_WITH COVID-19
Subject
Thrombosis of blood vessel
Predicate
COEXISTS_WITH
Object
COVID-19
9. COVID-19 PROCESS_OF Adult
Subject
COVID-19
Predicate
PROCESS_OF
Object
Adult
10. COVID-19 PROCESS_OF Child
Subject
COVID-19
Predicate
PROCESS_OF
Object
Child
11. Coagulation procedure CAUSES Complication
Subject
Coagulation procedure
Predicate
CAUSES
Object
Complication
12. Thrombosis COEXISTS_WITH COVID-19
Subject
Thrombosis
Predicate
COEXISTS_WITH
Object
COVID-19
13. Malaise PROCESS_OF Patients
Subject
Malaise
Predicate
PROCESS_OF
Object
Patients
14. Lymphohistiocytosis, Hemophagocytic PROCESS_OF Patients
Subject
Lymphohistiocytosis, Hemophagocytic
Predicate
PROCESS_OF
Object
Patients
15. Present COEXISTS_WITH Influenza
Subject
Present
Predicate
COEXISTS_WITH
Object
Influenza
16. Present COEXISTS_WITH Pulmonary thrombosis
Subject
Present
Predicate
COEXISTS_WITH
Object
Pulmonary thrombosis
17. Genes CAUSES Familial Hemophagocytic Lymphocytosis
Subject
Genes
Predicate
CAUSES
Object
Familial Hemophagocytic Lymphocytosis
18. Pulmonary Thromboembolisms COEXISTS_WITH 2019 novel coronavirus
Subject
Pulmonary Thromboembolisms
Predicate
COEXISTS_WITH
Object
2019 novel coronavirus
19. Thrombosis of blood vessel COEXISTS_WITH COVID-19
Subject
Thrombosis of blood vessel
Predicate
COEXISTS_WITH
Object
COVID-19
20. COVID-19 PROCESS_OF Adult
Subject
COVID-19
Predicate
PROCESS_OF
Object
Adult
21. COVID-19 PROCESS_OF Child
Subject
COVID-19
Predicate
PROCESS_OF
Object
Child
22. Coagulation procedure CAUSES Complication
Subject
Coagulation procedure
Predicate
CAUSES
Object
Complication
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Lymphohistiocytosis, Hemophagocytic / Extracellular Traps / SARS-CoV-2 / COVID-19 / Models, Biological Type of study: Etiology study Limits: Humans Language: English Journal: PLoS Comput Biol Journal subject: Biology / Medical Informatics Year: 2021 Document Type: Article Affiliation country: Journal.pcbi.1008810

Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Lymphohistiocytosis, Hemophagocytic / Extracellular Traps / SARS-CoV-2 / COVID-19 / Models, Biological Type of study: Etiology study Limits: Humans Language: English Journal: PLoS Comput Biol Journal subject: Biology / Medical Informatics Year: 2021 Document Type: Article Affiliation country: Journal.pcbi.1008810