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Risk stratification of patients with SARS-CoV-2 by tissue factor expression in circulating extracellular vesicles.

Abstract
Inflammatory response following SARS-CoV-2 infection results in substantial increase of amounts of intravascular pro-coagulant extracellular vesicles (EVs) expressing tissue factor (CD142) on their surface. CD142-EV turned out to be useful as diagnostic biomarker in COVID-19 patients. Here we aimed at studying the prognostic capacity of CD142-EV in SARS-CoV-2 infection. Expression of CD142-EV was evaluated in 261 subjects admitted to hospital for pneumonia and with a positive molecular test for SARS-CoV-2. The study population consisted of a discovery cohort of selected patients (n = 60) and an independent validation cohort including unselected consecutive enrolled patients (n = 201). CD142-EV levels were correlated with post-hospitalization course of the disease and compared to the clinically available 4C Mortality Score as referral. CD142-EV showed a reliable performance to predict patient prognosis in the discovery cohort (AUC = 0.906) with an accuracy of 81.7%, that was confirmed in the validation cohort (AUC = 0.736). Kaplan-Meier curves highlighted a high discrimination power in unselected subjects with CD142-EV being able to stratify the majority of patients according to their prognosis. We obtained a comparable accuracy, being not inferior in terms of prediction of patients' prognosis and risk of mortality, with 4C Mortality Score. The expression of surface vesicular CD142 and its reliability as prognostic marker was technically validated using different immunocapture strategies and assays. The detection of CD142 on EV surface gains considerable interest as risk stratification tool to support clinical decision making in COVID-19.
AuthorsJacopo Burrello, Elena Caporali, Lorenzo Grazioli Gauthier, Enea Pianezzi, Carolina Balbi, Elia Rigamonti, Sara Bolis, Edoardo Lazzarini, Vanessa Biemmi, Alessio Burrello, Roberto Frigerio, Gladys Martinetti, Tanja Fusi-Schmidhauser, Giuseppe Vassalli, Enrico Ferrari, Tiziano Moccetti, Alessandro Gori, Marina Cretich, Giorgia Melli, Silvia Monticone, Lucio Barile
JournalVascular pharmacology (Vascul Pharmacol) Vol. 145 Pg. 106999 (08 2022) ISSN: 1879-3649 [Electronic] United States
PMID35597450 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2022 Elsevier Inc. All rights reserved.
Chemical References
  • Biomarkers
  • Thromboplastin
Topics
  • Biomarkers (metabolism)
  • COVID-19 (diagnosis)
  • Extracellular Vesicles (metabolism)
  • Humans
  • Reproducibility of Results
  • Risk Assessment (methods)
  • SARS-CoV-2
  • Thromboplastin (metabolism)

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