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  3. Role of microbiota-derived corisin in coagulation activation during SARS-CoV-2 infection

Role of microbiota-derived corisin in coagulation activation during SARS-CoV-2 infection

  • J Thromb Haemost. 2024 Jul;22(7):1919-1935. doi: 10.1016/j.jtha.2024.02.014.
Tatsuki Tsuruga 1,  Hajime Fujimoto 1,  Taro Yasuma 2,  Corina N D'Alessandro-Gabazza 3,  Masaaki Toda 4,  Toshiyuki Ito 1,  Atsushi Tomaru 1,  Haruko Saiki 1,  Tomohito Okano 1,  Manal A B Alhawsawi 5,  Atsuro Takeshita 6,  Kota Nishihama 7,  Reoto Takei 8,  Yasuhiro Kondoh 8,  Isaac Cann 9,  Esteban C Gabazza 10,  Tetsu Kobayashi 11
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan.
  • 2 Department of Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan; Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan; Microbiome Research Center, Mie University, Tsu, Mie, Japan; Department of Diabetes, Endocrinology and Metabolism, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan.
  • 3 Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan; Microbiome Research Center, Mie University, Tsu, Mie, Japan; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
  • 4 Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan.
  • 5 Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
  • 6 Department of Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan; Department of Diabetes, Endocrinology and Metabolism, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan.
  • 7 Department of Diabetes, Endocrinology and Metabolism, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan.
  • 8 Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Aichi, Japan.
  • 9 Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois, USA; Department of Animal Science, University of Illinois Urbana-Champaign, Urbana, Illinois, USA; Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
  • 10 Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan; Microbiome Research Center, Mie University, Tsu, Mie, Japan; Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA. Electronic address: [email protected].
  • 11 Department of Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Tsu, Mie, Japan; Microbiome Research Center, Mie University, Tsu, Mie, Japan.
PMID: 38453025 DOI: 10.1016/j.jtha.2024.02.014
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.

Keywords

COVID-19; apoptosis; coagulation; corisin; inflammation; microbiota.

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