Circulating extracellular vesicles are endowed with enhanced procoagulant activity in SARS-CoV-2 infection.
Adult
Aged
Aged, 80 and over
Antigens, Surface
/ analysis
Biomarkers
/ analysis
COVID-19
/ blood
Case-Control Studies
Diagnosis, Differential
Extracellular Vesicles
/ immunology
Female
Humans
Male
Middle Aged
Nasopharynx
/ virology
SARS-CoV-2
/ isolation & purification
Switzerland
Thromboplastin
/ metabolism
Thrombosis
/ blood
Tumor Necrosis Factor-alpha
/ blood
Coagulation
Extracellular vesicles
Pneumonia
SARS-CoV-2
Tissue factor
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
18
01
2021
revised:
26
03
2021
accepted:
14
04
2021
pubmed:
11
5
2021
medline:
9
6
2021
entrez:
10
5
2021
Statut:
ppublish
Résumé
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. 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. 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. 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. Cardiocentro Ticino Institute, Ente ospedaliero Cantonale, Lugano-Switzerland.
Sections du résumé
BACKGROUND
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
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
RESULTS
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
CONCLUSIONS
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
BACKGROUND
Cardiocentro Ticino Institute, Ente ospedaliero Cantonale, Lugano-Switzerland.
Identifiants
pubmed: 33971404
pii: S2352-3964(21)00162-6
doi: 10.1016/j.ebiom.2021.103369
pmc: PMC8104913
pii:
doi:
Substances chimiques
Antigens, Surface
0
Biomarkers
0
TNF protein, human
0
Tumor Necrosis Factor-alpha
0
Thromboplastin
9035-58-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103369Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Authors have nothing to disclose.