Cell Communication and Signaling (Feb 2025)

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

  • Yao Liao,
  • Yuheng Liu,
  • Dinghao Li,
  • Shiqi Luo,
  • Yun Huang,
  • Junwei Wu,
  • Jin Su,
  • Yi Yang,
  • Ji Wu,
  • Zifeng Zhu,
  • Mengxi Yanglan,
  • Haiyi Deng,
  • Xinyi Wu,
  • Junhao Xu,
  • Feiyang Cao,
  • Chunmei Cai,
  • Zhen Li,
  • Ruibing Yang,
  • Xiaoyan Deng,
  • Jie Wei,
  • Lifu Wang

DOI
https://doi.org/10.1186/s12964-025-02095-1
Journal volume & issue
Vol. 23, no. 1
pp. 1 – 13

Abstract

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Abstract 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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