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Peripheral blood mononuclear cell tissue factor (F3 gene) transcript levels and circulating extracellular vesicles are elevated in severe coronavirus 2019 (COVID-19) disease.
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.
  • Girard TJ; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Antunes L; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Zhang N; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Amrute JM; Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Subramanian R; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Eldem I; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Remy KE; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Mazer M; Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Erlich EC; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Cruchaga C; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Steed AL; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Randolph GJ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
  • Di Paola J; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA. Electronic address: dipaolaj@wustl.edu.
J Thromb Haemost ; 21(3): 629-638, 2023 03.
Article in English | MEDLINE | ID: covidwho-2260707
ABSTRACT

BACKGROUND:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with excessive coagulation, thrombosis, and mortality.

OBJECTIVE:

To provide insight into mechanisms that contribute to excessive coagulation in coronavirus 2019 (COVID-19) disease. PATIENTS/

METHODS:

Blood from COVID-19 patients was investigated for coagulation-related gene expression and functional activities.

RESULTS:

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.

CONCLUSIONS:

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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Blood Coagulation Disorders / Extracellular Vesicles / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Humans Language: English Journal: J Thromb Haemost Journal subject: Hematology Year: 2023 Document Type: Article Affiliation country: J.jtha.2022.11.033

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Blood Coagulation Disorders / Extracellular Vesicles / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Humans Language: English Journal: J Thromb Haemost Journal subject: Hematology Year: 2023 Document Type: Article Affiliation country: J.jtha.2022.11.033