Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection
Carolina Balbi,
Jacopo Burrello,
Sara Bolis,
Edoardo Lazzarini,
Vanessa Biemmi,
Enea Pianezzi,
Alessio Burrello,
Elena Caporali,
Lorenzo Gauthier Grazioli,
Gladys Martinetti,
Tanja Fusi-Schmidhauser,
Giuseppe Vassalli,
Giorgia Melli,
Lucio Barile
Affiliations
Carolina Balbi
Laboratory of Cellular and Molecular Cardiology, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale, Lugano, Switzerland; Center for Molecular Cardiology, Zurich, Switzerland
Jacopo Burrello
Laboratory for Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale Lugano, Switzerland
Sara Bolis
Laboratory of Cellular and Molecular Cardiology, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale, Lugano, Switzerland; Laboratory for Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale Lugano, Switzerland
Edoardo Lazzarini
Laboratory for Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale Lugano, Switzerland
Vanessa Biemmi
Laboratory for Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale Lugano, Switzerland
Enea Pianezzi
Laboratory of Microbiology, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Alessio Burrello
Department of Electrical, Electronic and Information Engineering (DEI), University of Bologna, Bologna, Italy
Elena Caporali
Cardiology Department, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale, Lugano, Switzerland
Lorenzo Gauthier Grazioli
Internal Medicine Department, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland
Gladys Martinetti
Laboratory of Microbiology, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Tanja Fusi-Schmidhauser
Internal Medicine Department, Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale, Lugano, Switzerland
Giuseppe Vassalli
Laboratory of Cellular and Molecular Cardiology, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale, Lugano, Switzerland; Center for Molecular Cardiology, Zurich, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland
Giorgia Melli
Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland; Laboratory for Biomedical Neurosciences, Neurocenter of Southern Switzerland, Lugano, Switzerland
Lucio Barile
Laboratory for Cardiovascular Theranostics, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale Lugano, Switzerland; Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland; Institute of Life Science, Scuola Superiore Sant'Anna, Pisa, Italy; Corresponding author at: Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale, Via Tesserete 48, 6900 Lugano, Switzerland.
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-α 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-α 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.
