Extensive fibrin deposition in the lungs and altered levels of circulating blood coagulation proteins in COVID-19 patients imply local derangement of pathways that limit fibrin formation and/or promote its clearance. We examined transcriptional profiles of bronchoalveolar lavage fluid (BALF) samples to identify molecular mechanisms underlying these coagulopathies. mRNA levels for regulators of the kallikrein-kinin (C1-inhibitor), coagulation (thrombomodulin, endothelial protein C receptor), and fibrinolytic (urokinase and urokinase receptor) pathways were significantly reduced in COVID-19 patients. While transcripts for several coagulation proteins were increased, those encoding tissue factor, the protein that initiates coagulation and whose expression is frequently increased in inflammatory disorders, were not increased in BALF from COVID-19 patients. Our analysis implicates enhanced propagation of coagulation and decreased fibrinolysis as drivers of the coagulopathy in the lungs of COVID-19 patients.
All data generated or analysed during this study are included in the manuscript and supporting files. Data for control and COVID-19 bronchoalveolar lavage samples are available in the Sequence Read Archive at NCBI.
Severe acute respiratory syndrome coronavirus 2 Raw sequence readsNCBI, PRJNA605983.
- Michael R Garvin
- Christiane Alvarez
- J Izaak Miller
- Daniel Jacobson
- Bruce Aronow
- Alan E Mast
- Alisa S Wolberg
- Alisa S Wolberg
- David Gailani
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Noriaki Emoto, Kobe Pharmaceutical University, Japan
© 2021, Mast et al.
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