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

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, Lisa Olano, Joseph Brzostowski, Elizabeth R. Fischer, Homer L. Twigg, Reed F. Johnson and Peter D. Sun ()
Additional contact information
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

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42140-6

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