TY - JOUR
T1 - Role of microbiota-derived corisin in coagulation activation during SARS-CoV-2 infection
AU - Tsuruga, Tatsuki
AU - Fujimoto, Hajime
AU - Yasuma, Taro
AU - D'Alessandro-Gabazza, Corina N.
AU - Toda, Masaaki
AU - Ito, Toshiyuki
AU - Tomaru, Atsushi
AU - Saiki, Haruko
AU - Okano, Tomohito
AU - Alhawsawi, Manal A.B.
AU - Takeshita, Atsuro
AU - Nishihama, Kota
AU - Takei, Reoto
AU - Kondoh, Yasuhiro
AU - Cann, Isaac
AU - Gabazza, Esteban C.
AU - Kobayashi, Tetsu
N1 - Funding information This study was financially supported in part by grants from the Japan Society for the Promotion of Science (Grant number 22K08280), the Japan Science and Technology Agency (Grant number JPMJFR2216), the 2022 Suzuken Memorial Foundation , the 2022 Yokoyama Foundation for Clinical Pharmacology, the 2022 Japan Diabetes Foundation / Novo Nordisk Pharma Ltd, the 2022 Takeda Science Foundation , and the 2023 Takeda Science Foundation. The research of I.C. was supported by the Charles and Margaret Levin Foundation.
Funding information This study was financially supported in part by grants from the Japan Society for the Promotion of Science (Grant numbers 23K07651 and 22K08280), the Japan Science and Technology Agency (Grant number JPMJFR2216), the 2022 Suzuken Memorial Foundation, the 2022 Yokoyama Foundation for Clinical Pharmacology, the 2022 Japan Diabetes Foundation/Novo Nordisk Pharma Ltd, the 2022 Takeda Science Foundation, and the 2023 Takeda Science Foundation. The research of I.C. was supported by the Charles and Margaret Levin Foundation.
PY - 2024/7
Y1 - 2024/7
N2 - 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.
AB - 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.
KW - COVID-19
KW - apoptosis
KW - coagulation
KW - corisin
KW - inflammation
KW - microbiota
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U2 - 10.1016/j.jtha.2024.02.014
DO - 10.1016/j.jtha.2024.02.014
M3 - Article
C2 - 38453025
AN - SCOPUS:85188827895
SN - 1538-7933
VL - 22
SP - 1919
EP - 1935
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
IS - 7
ER -