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- Title
SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition.
- Authors
Erickson, Rachel; Huang, Chang; Allen, Cameron; Ireland, Joanna; Roth, Gwynne; Zou, Zhongcheng; Lu, Jinghua; Lafont, Bernard A. P.; Garza, Nicole L.; Brumbaugh, Beniah; Zhao, Ming; Suzuki, Motoshi; Olano, Lisa; Brzostowski, Joseph; Fischer, Elizabeth R.; Twigg III, Homer L.; Johnson, Reed F.; Sun, Peter D.
- 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. Severe SARS-CoV-2 infection has been associated with extensive diffuse alveolar damage and fibrin formation. Here, Erickson et al describe an infection-induced coagulation mechanism which involves activation of prothrombin by members of TMPRSS genes.
- Subjects
EPITHELIAL cells; BLOOD coagulation factors; FIBRIN; LUNG infections; SARS-CoV-2; SERINE proteinases; BLOOD coagulation factor X
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-42140-6