We showed that COVID-19 patient–derived EVs or viral spike protein triggered-pEVs that carried GU-enriched miRNAs (e.g., miR-21/let-7b) interacted with TLR7/8 to induce p47phox phosphorylation, activate NADPH oxidase and thus promote ROS production in neutrophils to enhance NETs formation. The gene discussed is NCF1; the disease is COVID-19.