Role of Microbiota-Derived Corisin in Coagulation Activation during SARS-CoV-2 Infection.

COVID-19 apoptosis coagulation corisin inflammation microbiota

Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
05 Mar 2024
Historique:
received: 27 09 2023
revised: 23 01 2024
accepted: 13 02 2024
medline: 8 3 2024
pubmed: 8 3 2024
entrez: 7 3 2024
Statut: aheadofprint

Résumé

Coagulopathy is a major cause of morbidity and mortality in COVID-19 patients. Hypercoagulability in COVID-19 results in deep vein thrombosis, thromboembolic complications, and diffuse intravascular coagulation. Microbiome dysbiosis influences the clinical course of COVID-19. However, the role of dysbiosis in COVID-19-associated coagulopathy is not fully understood. The present study tested the hypothesis that the microbiota-derived proapoptotic corisin is involved in the coagulation system activation during SARS-CoV-2 infection. This cross-sectional study included 47 consecutive patients who consulted for symptoms of COVID-19. A mouse acute lung injury model was used to recapitulate the clinical findings. A549 alveolar epithelial, THP-1 and human umbilical vein endothelial cells were used to evaluate procoagulant and anticoagulant activity of corisin. COVID-19 patients showed significantly high circulating levels of corisin, thrombin-antithrombin complex, D-dimer, soluble thrombomodulin, tumor necrosis factor-α, and monocyte-chemoattractant protein-1 with reduced levels of free protein S compared to healthy subjects. The levels of thrombin-antithrombin complex, D-dimer, and corisin were significantly correlated. A monoclonal anticorisin neutralizing antibody significantly inhibited the inflammatory response and coagulation system activation in a SARS-CoV-2 spike protein-associated acute lung injury mouse model, and the levels of corisin and thrombin-antithrombin complex were significantly correlated. In an in vitro experiment, corisin increased the tissue factor activity and decreased the anticoagulant activity of thrombomodulin in epithelial, endothelial and monocytic cells. The microbiota-derived corisin is significantly increased and correlated with activation of the coagulation system during SARS-CoV-2 infection, and corisin may directly increase the procoagulant activity in epithelial, endothelial and monocytic cells.

Sections du résumé

BACKGROUND BACKGROUND
Coagulopathy is a major cause of morbidity and mortality in COVID-19 patients. Hypercoagulability in COVID-19 results in deep vein thrombosis, thromboembolic complications, and diffuse intravascular coagulation. Microbiome dysbiosis influences the clinical course of COVID-19. However, the role of dysbiosis in COVID-19-associated coagulopathy is not fully understood.
OBJECTIVES OBJECTIVE
The present study tested the hypothesis that the microbiota-derived proapoptotic corisin is involved in the coagulation system activation during SARS-CoV-2 infection.
METHODS METHODS
This cross-sectional study included 47 consecutive patients who consulted for symptoms of COVID-19. A mouse acute lung injury model was used to recapitulate the clinical findings. A549 alveolar epithelial, THP-1 and human umbilical vein endothelial cells were used to evaluate procoagulant and anticoagulant activity of corisin.
RESULTS RESULTS
COVID-19 patients showed significantly high circulating levels of corisin, thrombin-antithrombin complex, D-dimer, soluble thrombomodulin, tumor necrosis factor-α, and monocyte-chemoattractant protein-1 with reduced levels of free protein S compared to healthy subjects. The levels of thrombin-antithrombin complex, D-dimer, and corisin were significantly correlated. A monoclonal anticorisin neutralizing antibody significantly inhibited the inflammatory response and coagulation system activation in a SARS-CoV-2 spike protein-associated acute lung injury mouse model, and the levels of corisin and thrombin-antithrombin complex were significantly correlated. In an in vitro experiment, corisin increased the tissue factor activity and decreased the anticoagulant activity of thrombomodulin in epithelial, endothelial and monocytic cells.
CONCLUSION CONCLUSIONS
The microbiota-derived corisin is significantly increased and correlated with activation of the coagulation system during SARS-CoV-2 infection, and corisin may directly increase the procoagulant activity in epithelial, endothelial and monocytic cells.

Identifiants

DOI: 10.1016/j.jtha.2024.02.014 PMID: 38453025
pubmed: 38453025
pii: S1538-7836(24)00118-1
doi: 10.1016/j.jtha.2024.02.014
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Auteurs

Tatsuki Tsuruga (T)

Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Hajime Fujimoto (H)

Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Taro Yasuma (T)

Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan; Department of Immunology, Faculty and Graduate School of Medicin, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan; Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Corina N D'Alessandro-Gabazza (CN)

Department of Immunology, Faculty and Graduate School of Medicin, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan; Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Masaaki Toda (M)

Department of Immunology, Faculty and Graduate School of Medicin, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Toshiyuki Ito (T)

Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Atsushi Tomaru (A)

Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Haruko Saiki (H)

Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Tomohito Okano (T)

Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Manal A B Alhawsawi (MAB)

Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Atsuro Takeshita (A)

Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan; Department of Diabetes, Endocrinology and Metabolism, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Kota Nishihama (K)

Department of Diabetes, Endocrinology and Metabolism, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Reoto Takei (R)

Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-Cho, Seto, Aichi 489-8642 Japan.

Yasuhiro Kondoh (Y)

Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-Cho, Seto, Aichi 489-8642 Japan.

Isaac Cann (I)

Department of Animal Science, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Esteban C Gabazza (EC)

Department of Immunology, Faculty and Graduate School of Medicin, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan; Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address: gabazza@doc.medic.mie-u.ac.jp.

Tetsu Kobayashi (T)

Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan; Microbiome Research Center, Mie University, Edobashi 2-174, Tsu, Mie 514-8507, Japan.

Classifications MeSH