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

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.
Competing Interests: AM receives research funding from Novo Nordisk and has received honoraria for serving on Novo Nordisk advisory boards. AW receives research funding from Takeda and Bristol Myers Squibb, DG receives research funding from Bayer and has received honoraria for serving on Anthos, Bristol-Myers Squibb, Ionis and Janssen advisory boards. MG, CA, JM, BA, DJ No competing interests declared
(© 2021, Mast et al.)