EVs from severe COVID-19 patients enhanced the responsiveness of Vδ2 T cells to phosphoantigen, increasing their activation and proinflammatory cytokine production (TNF-α).<h4>Conclusions</h4>Proteomic differential analysis reveals the expression/regulation of innate immune-related proteins in EVs from severe patients compared to mild patients/HD and supports their potential role in modulating innate immunity. This evidence concerns the gene TNF and COVID-19.