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SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition

Author

Listed:
  • Rachel Erickson

    (National Institutes of Health)

  • Chang Huang

    (National Institutes of Health)

  • Cameron Allen

    (National Institutes of Health)

  • Joanna Ireland

    (National Institutes of Health)

  • Gwynne Roth

    (National Institutes of Health)

  • Zhongcheng Zou

    (National Institutes of Health)

  • Jinghua Lu

    (National Institutes of Health)

  • Bernard A. P. Lafont

    (National Institutes of Health)

  • Nicole L. Garza

    (National Institutes of Health)

  • Beniah Brumbaugh

    (National Institutes of Health)

  • Ming Zhao

    (National Institutes of Health)

  • Motoshi Suzuki

    (National Institutes of Health)

  • Lisa Olano

    (National Institutes of Health)

  • Joseph Brzostowski

    (National Institutes of Health)

  • Elizabeth R. Fischer

    (National Institutes of Health)

  • Homer L. Twigg

    (Indiana University Medical Center)

  • Reed F. Johnson

    (National Institutes of Health)

  • Peter D. Sun

    (National Institutes of Health)

Abstract

Severe COVID-associated lung injury is a major confounding factor of hospitalizations and death with no effective treatments. Here, we describe a non-classical fibrin clotting mechanism mediated by SARS-CoV-2 infected primary lung but not other susceptible epithelial cells. This infection-induced fibrin formation is observed in all variants of SARS-CoV-2 infections, and requires thrombin but is independent of tissue factor and other classical plasma coagulation factors. While prothrombin and fibrinogen levels are elevated in acute COVID BALF samples, fibrin clotting occurs only with the presence of viral infected but not uninfected lung epithelial cells. We suggest a viral-induced coagulation mechanism, in which prothrombin is activated by infection-induced transmembrane serine proteases, such as ST14 and TMPRSS11D, on NHBE cells. Our finding reveals the inefficiency of current plasma targeted anticoagulation therapy and suggests the need to develop a viral-induced ARDS animal model for treating respiratory airways with thrombin inhibitors.

Suggested Citation

  • Rachel Erickson & Chang Huang & Cameron Allen & Joanna Ireland & Gwynne Roth & Zhongcheng Zou & Jinghua Lu & Bernard A. P. Lafont & Nicole L. Garza & Beniah Brumbaugh & Ming Zhao & Motoshi Suzuki & Li, 2023. "SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42140-6
    DOI: 10.1038/s41467-023-42140-6
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    3. Johannes C. Melms & Jana Biermann & Huachao Huang & Yiping Wang & Ajay Nair & Somnath Tagore & Igor Katsyv & André F. Rendeiro & Amit Dipak Amin & Denis Schapiro & Chris J. Frangieh & Adrienne M. Luom, 2021. "A molecular single-cell lung atlas of lethal COVID-19," Nature, Nature, vol. 595(7865), pages 114-119, July.
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