Fig. 1

Circulating EVs induced NETs formation in COVID-19 patients. A Increased levels of NETs DNA were detected in the plasma from COVID-19 patients with different severities compared to those in healthy control (HC) subjects. B Elevated NETs DNA was released from normal human neutrophils treating plasma from COVID-19 patients. C Transmission electron micrographs of purified extracellular vesicles (EVs) isolated from HC (upper panel) and COVID-19 patient (lower panel). The scale bar in the image represents 100 nm. D The size distribution of EVs isolated from HC (upper panel) and COVID-19 patient (lower panel) were analyzed using a nanoparticle tracking assay. E Expression of small EV (sEV)-specific surface markers CD63, CD81, CD9, TSG101 (Tumor Susceptibility Gene 101) and Alix (ALG-2-interacting protein X) in plasma–derived EVs was analyzed using immunoblotting. F Comparison of plasma–derived EVs levels in COVID-19 patients with different severity and HC subjects. The plasma–derived EV levels in patients were quantified using enzyme-linked immunosorbent assay (ELISA)-based assay. G Increased levels of NETs DNA were detected in normal human neutrophils after treating with COVID-19 patient–derived EVs (left panel); this effect was decreased in the presence of the endocytosis inhibitor cytochalasin D (Cyt D, 10 μM) (middle panel). H The quantification of NETs DNA released from normal human neutrophils with different stimulation. The scale bar in the IFA image represents 5 μm. All experiments were performed in triplicate and data were presented as mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.005