SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung
Abstract
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.
Data availability
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.
Article and author information
Author details
Funding
Oak Ridge National Laboratory (LOIS:10074)
- Michael R Garvin
- Christiane Alvarez
- J Izaak Miller
- Daniel Jacobson
National Institutes of Health (U24 HL148865)
- Bruce Aronow
National Institutes of Health (HL068835)
- Alan E Mast
National Institutes of Health (HL143403)
- Alisa S Wolberg
National Institutes of Health (HL126974)
- Alisa S Wolberg
National Institutes of Health (HL140025)
- David Gailani
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Noriaki Emoto, Kobe Pharmaceutical University, Japan
Version history
- Received: October 26, 2020
- Accepted: March 6, 2021
- Accepted Manuscript published: March 8, 2021 (version 1)
- Accepted Manuscript updated: March 9, 2021 (version 2)
- Version of Record published: April 15, 2021 (version 3)
Copyright
© 2021, Mast et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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