Oak Ridge National Laboratory, Biosciences Division, Oak Ridge, United States
Christiane Alvarez
Oak Ridge National Laboratory, Biosciences Division, Oak Ridge, United States
J Izaak Miller
Oak Ridge National Laboratory, Biosciences Division, Oak Ridge, United States
Bruce Aronow
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
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.
