Extracellular Vesicles in COVID-19 convalescence can regulate T cell metabolism and function

Long-term T cell dysregulation has been reported following COVID-19 disease. Prolonged T cell activation is associated with initial disease severity and may be implicated mechanistically in the onset of long-covid symptoms. Here we assess the role of extracellular vesicles (EV) in regulating T cell function over several weeks post COVID-19 infection. We find both the cellular origin and protein content of EV was altered in COVID-19 convalescent individuals compared to healthy donors, with alterations linked to initial disease severity. We demonstrate that convalescent donor-derived EV can alter the function and metabolic rewiring of both CD4 and CD8 T cells. Of note, EV following mild, but not severe disease, show distinctly immunesuppressive properties, reducing T cell effector cytokine production and glucose metabolism. Mechanistically our data indicate the involvement of EV-surface ICAM-1 in facilitating EV - T cell interaction. Taken together, our data demonstrate that circulatory EV are phenotypically and functionally altered several weeks following acute infection, suggesting a role for EV as long-term immune modulators.