Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection

被引：76

作者：

Balbi, Carolina ^{[1
,2
]}

Burrello, Jacopo ^{[3
]}

Bolis, Sara ^{[1
,3
]}

Lazzarini, Edoardo ^{[3
]}

Biemmi, Vanessa ^{[3
]}

Pianezzi, Enea ^{[4
,6
]}

Burrello, Alessio ^{[5
]}

Caporali, Elena ^{[6
]}

Grazioli, Lorenzo Gauthier ^{[7
]}

Martinetti, Gladys ^{[4
]}

Fusi-Schmidhauser, Tanja ^{[7
]}

Vassalli, Giuseppe ^{[1
,2
,8
]}

Melli, Giorgia ^{[8
,9
]}

Barile, Lucio ^{[3
,8
,10
]}

机构：

[1] Ente Osped Cantonale, Lab Cellular & Mol Cardiol, Ist Cardioctr Ticino, Lugano, Switzerland

[2] Ctr Mol Cardiol, Zurich, Switzerland

[3] Ente Osped Cantonale Lugano, Ist Cardioctr Ticino, Lab Cardiovasc Theranost, Lugano, Switzerland

[4] Ente Osped Cantonale, Microbiol Lab, Bellinzona, Switzerland

[5] Univ Bologna, Dept Elect Elect & Informat Engn DEI, Bologna, Italy

[6] Ente Osped Cantonale, Cardiol Dept, Ist Cardioctr Ticino, Lugano, Switzerland

[7] Ente Osped Cantonale, Osped Reg Lugano, Internal Med Dept, Lugano, Switzerland

[8] Univ Svizzera Italiana, Fac Biomed Sci, Lugano, Switzerland

[9] Neuroctr Southern Switzerland, Lab Biomed Neurosci, Lugano, Switzerland

[10] Scuola Super Sant Anna, Inst Life Sci, Pisa, Italy

来源：

EBIOMEDICINE | 2021年 / 67卷

关键词：

Extracellular vesicles; SARS-CoV-2; Tissue factor; Pneumonia; Coagulation; PROTEIN DISULFIDE-ISOMERASE; TISSUE FACTOR ACTIVITY; INFLAMMATION; EXOSOMES; EXPRESSION; GENERATION; DISEASE; CELLS; ASSAY;

D O I：

10.1016/j.ebiom.2021.103369

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Coronavirus-2 (SARS-CoV-2) infection causes an acute respiratory syndrome accompanied by multi-organ damage that implicates a prothrombotic state leading to widespread microvascular clots. The causes of such coagulation abnormalities are unknown. The receptor tissue factor, also known as CD142, is often associated with cell-released extracellular vesicles (EV). In this study, we aimed to characterize surface antigens profile of circulating EV in COVID-19 patients and their potential implication as procoagulant agents. Methods: We analyzed serum-derived EV from 67 participants who underwent nasopharyngeal swabs molecular test for suspected SARS-CoV-2 infection (34 positives and 33 negatives) and from 16 healthy controls (HC), as referral. A sub-analysis was performed on subjects who developed pneumonia (n = 28). Serum-derived EV were characterized for their surface antigen profile and tested for their procoagulant activity. A validation experiment was performed pre-treating EV with anti-CD142 antibody or with recombinant FVIIa. Serum TNF-alpha levels were measured by ELISA. Findings: Profiling of EV antigens revealed a surface marker signature that defines circulating EV in COVID-19. A combination of seven surface molecules (CD49e, CD209, CD86, CD133/1, CD69, CD142, and CD20) clustered COVID (+) versus COVID (-) patients and HC. CD142 showed the highest discriminating performance at both multivariate models and ROC curve analysis. Noteworthy, we found that CD142 exposed onto surface of EV was biologically active. CD142 activity was higher in COVID (+) patients and correlated with TNF-alpha serum levels. Interpretation: In SARS-CoV-2 infection the systemic inflammatory response results in cell-release of substantial amounts of procoagulant EV that may act as clotting initiation agents, contributing to disease severity. Funding: Cardiocentro Ticino Institute, Ente ospedaliero Cantonale, Lugano-Switzerland. (C) 2021 The Author(s). Published by Elsevier B.V.

引用

页数：12