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

Alan E. Mast; Alisa S. Wolberg; David Gailani; Michael R. Garvin; Christiane Alvarez; J. Izaak Miller; Bruce Aronow; Daniel Jacobson

doi:10.7554/eLife.64330

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

Alan E. Mast, Alisa S. Wolberg, David Gailani, Michael R. Garvin, Christiane Alvarez, J. Izaak Miller, Bruce Aronow, Daniel Jacobson

Computational and Predictive Biology

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

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.

Original language	English
Article number	e64330
Journal	eLife
Volume	10
DOIs	https://doi.org/10.7554/eLife.64330
State	Published - Mar 2021

Funding

was also provided by the National Institutes of Health grants HL068835 (AM), HL143403 (AW), HL126974 (AW), and HL140025 (DG) to support analyses and interpretation of the coagulation and fibrinolytic pathways. This research used resources of the Oak Ridge Leadership Computing Facility, which is a DOE Office of Science User Facility supported under Contract DE-AC05-00OR22725. This research used resources of the Compute and Data Environment for Science (CADES) at the Oak Ridge National Laboratory.

Funders	Funder number
CADES
Data Environment for Science
National Institutes of Health	HL126974, HL140025, HL068835, HL143403
National Heart, Lung, and Blood Institute	U24HL148865
Office of Science	DE-AC05-00OR22725
Oak Ridge National Laboratory

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7554/eLife.64330

Cite this

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title = "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.",

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AU - Mast, Alan E.

AU - Wolberg, Alisa S.

AU - Gailani, David

AU - Garvin, Michael R.

AU - Alvarez, Christiane

AU - Izaak Miller, J.

AU - Aronow, Bruce

AU - Jacobson, Daniel

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AB - 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.

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

Abstract

Funding

UN SDGs

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