1. Role of microbiota-derived corisin in coagulation activation during SARS-CoV-2 infection.
- Author
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Tsuruga T, Fujimoto H, Yasuma T, D'Alessandro-Gabazza CN, Toda M, Ito T, Tomaru A, Saiki H, Okano T, Alhawsawi MAB, Takeshita A, Nishihama K, Takei R, Kondoh Y, Cann I, Gabazza EC, and Kobayashi T
- Subjects
- Humans, Animals, Male, Female, Middle Aged, Cross-Sectional Studies, Mice, A549 Cells, Acute Lung Injury microbiology, Acute Lung Injury blood, THP-1 Cells, Aged, Disease Models, Animal, Microbiota, Dysbiosis, Adult, Antithrombin III, Mice, Inbred C57BL, Peptide Hydrolases, COVID-19 blood, COVID-19 complications, COVID-19 immunology, Blood Coagulation, SARS-CoV-2, Human Umbilical Vein Endothelial Cells
- Abstract
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: 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: 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: COVID-19 patients showed significantly high circulating levels of corisin, thrombin-antithrombin complex, D-dimer, tumor necrosis factor-α, and monocyte-chemoattractant protein-1 with reduced levels of free protein S compared with 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: 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., Competing Interests: Declaration of competing interests E.C.G., C.N.D.'A.-G., and I.C. hold patents on corisin and the anticorisin monoclonal antibody reported in this study. The other authors declare no competing interests related to this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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