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SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung

Journal Article · · eLife
DOI:https://doi.org/10.7554/eLife.64330· OSTI ID:1769526
 [1];  [2];  [3];  [4];  [4];  [4];  [5];  [6]
  1. Versiti Blood Research Institute, Department of Cell Biology Neurobiology and Anatomy Medical College of Wisconsin, Milwaukee, United States
  2. Department of Pathology and Laboratory Medicine and UNC Blood Research Center, Chapel Hill, United States
  3. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, United States
  4. Oak Ridge National Laboratory, Biosciences Division, Oak Ridge, United States
  5. University of Tennessee Knoxville, The Bredesen Center for Interdisciplinary Research and Graduate Education, Knoxville, United States, Biomedical Informatics, Cincinnati Children’s Hospital Research Foundation, Cincinnati, United States, University of Cincinnati, Cincinnati, United States
  6. Oak Ridge National Laboratory, Biosciences Division, Oak Ridge, United States, University of Tennessee Knoxville, The Bredesen Center for Interdisciplinary Research and Graduate Education, Knoxville, United States, University of Tennessee Knoxville, Department of Psychology, Knoxville, United States

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.

Research Organization:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC05-00OR22725
OSTI ID:
1769526
Alternate ID(s):
OSTI ID: 1814387
OSTI ID: 1769527
Journal Information:
eLife, Journal Name: eLife Vol. 10; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
English

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