Peripheral blood mononuclear cell tissue factor (F3 gene) transcript levels and circulating extracellular vesicles are elevated in severe coronavirus 2019 (COVID-19) disease

• Published in: Journal of thrombosis and haemostasis Vol. 21; no. 3; pp. 629 - 638
• Main Authors: Girard, Thomas J., Antunes, Lilian, Zhang, Nan, Amrute, Junedh M., Subramanian, Renumathi, Eldem, Irem, Remy, Kenneth E., Mazer, Monty, Erlich, Emma C., Cruchaga, Carlos, Steed, Ashley L., Randolph, Gwendalyn J., Di Paola, Jorge
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.03.2023
• Subjects: Blood Coagulation Disorders; coagulation; COVID-19; Extracellular Vesicles - metabolism; Humans; Leukocytes, Mononuclear - metabolism; SARS-CoV-2; Thromboplastin - metabolism; Thrombosis; tissue factor; transcriptome; COVID-19; thrombosis; tissue factor; coagulation; transcriptome
• ISSN: 1538-7836; 1538-7836
• DOI: 10.1016/j.jtha.2022.11.033

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with excessive coagulation, thrombosis, and mortality. To provide insight into mechanisms that contribute to excessive coagulation in coronavirus 2019 (COVID-19) disease. Blood from COVID-19 patients was investigated for coagulation–related gene expression and functional activities. Single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from severe COVID-19 patients revealed a 5.2-fold increase in tissue factor (TF [F3 gene]) transcript expression levels (P < .05), the trigger of extrinsic coagulation; a 7.7-fold increase in C1-inhibitor (SERPING1 gene; P < .01) transcript expression levels, an inhibitor of intrinsic coagulation; and a 4.4-fold increase in anticoagulant thrombomodulin (TM [THBD gene]) transcript expression levels (P < .001). Bulk RNA-seq analysis of sorted CD14+ monocytes on an independent cohort of COVID-19 patients confirmed these findings (P < .05). Indicative of excessive coagulation, 41% of COVID-19 patients’ plasma samples contained high D-dimer levels (P < .0001); of these, 19% demonstrated extracellular vesicle TF activity (P = .109). COVID-19 patients’ ex vivo plasma–based thrombin generation correlated positively with D-dimer levels (P < .01). Plasma procoagulant extracellular vesicles were elevated ∼9-fold in COVID-19 patients (P < .01). Public scRNA-seq data sets from bronchoalveolar lung fluid and our peripheral blood mononuclear cell scRNA-seq data show CD14+ monocytes/macrophages TF transcript expression levels are elevated in severe but not mild or moderate COVID-19 patients. Beyond local lung injury, SARS-CoV-2 infection increases systemic TF (F3) transcript levels and elevates circulating extracellular vesicles that likely contribute to disease-associated coagulation, thrombosis, and related mortality. •Severe coronavirus 2019 (COVID-19) disease is associated with thrombosis.•Circulating monocytes from patients with severe COVID-19 show elevated tissue factor transcripts.•Circulating procoagulant extracellular vesicles are also elevated.•Elevated monocyte tissue factor expression likely contributes to thrombosis in severe COVID-19 disease.