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Liao, Y.* ; Liu, Y.* ; Li, D.* ; Luo, S. ; Huang, Y.* ; Wu, J.* ; Su, J.* ; Yang, Y.* ; Zhu, Z.* ; Yanglan, M.* ; Deng, H.* ; Wu, X.* ; Xu, J.* ; Cao, F.* ; Cai, C.* ; Li, Z.* ; Yang, R.* ; Deng, X.* ; Wei, J.* ; Wang, L.*

COVID-19 patient serum-derived extracellular vesicles deliver miR-20b-5p induces neutrophil extracellular traps.

Cell Commun. Signal. 23:93 (2025)

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BACKGROUND: Severe cases of COVID-19 are characterized by an excessive presence of neutrophils. Neutrophil extracellular traps (NETs), released by activated neutrophils due to SARS-CoV-2 infection, contribute to lung epithelial cell death and are key drivers in COVID-19-associated immunothrombosis. However, the mechanism underlying NET formation in COVID-19 remain unclear. METHODS: Extracellular vesicles (EVs) were isolated from the serum of COVID-19 patients and healthy volunteers, while neutrophils were isolated from blood samples of healthy volunteers. Neutrophils were treated with EVs, and the formation of NETs was observed. To identify the components responsible for the COVID-19-EVs-induced NET formation, we analyzed the expression profiles of microRNA (miRNAs) in COVID-19-EVs. We identified eight highly expressed miRNAs in COVID-19-EVs and explored their potential roles in COVID-19-EVs-mediated NET formation. Additionally, we explored the role of miR-20b-5p in COVID-19-EVs-induced NET formation. RESULTS: In this study, we demonstrate that patients with COVID-19 have a higher concentration of serum EVs (COVID-19-EVs) than healthy controls (Normal-EVs). We also found that COVID-19-EVs are internalized by neutrophils to induced NET formation. Through comprehensive miRNA profiling of COVID-19-EVs versus Normal-EVs, we identified 78 differentially expressed miRNAs, with 27 of these being upregulated and 51 being downregulated. Subsequently, we discovered that COVID-19-EVs that were highly abundant with certain miRNAs promote NET formation. Specifically, miR-20b-5p was found to be the strongest inducer of NET formation of the identified miRNAs. Inhibition of miR-20b-5p resulted in a significant decrease in COVID-19-EVs-mediated induction of NET formation. CONCLUSION: Herein, we reveal a previously unknown role of COVID-19-EVs in NET formation, which contributes to COVID-19 progression. This study suggests that miR-20b-5p may serve as a potential therapeutic target for COVID-19 treatment.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Covid-19 ; Extracellular Vesicles ; Neutrophil Extracellular Traps ; Mir-20b-5p ; Mirnas; Cytokine Storm; Thrombosis; Receptors

ISSN (print) / ISBN 1478-811X

e-ISSN 1478-811X

Journal Cell Communication and Signaling

Quellenangaben Volume: 23, Issue: 1, Article Number: 93

Publisher BioMed Central

Publishing Place Campus, 4 Crinan St, London N1 9xw, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Virology (VIRO)

Grants Youth Innovation Talent Project of Ordinary university in Guangdong Province
Guangzhou key laboratory for clinical rapid diagnosis andearly warning of infectious diseases
Open Project of Guangzhou Medical University
Natural Science Foundation of Guangdong Province
National Natural Science Foundation of China
Department of Education of GuangDong Province
Science and Technology Plan Project of Guangzhou