Emerging roles of extracellular vesicles in COVID‐19, a double‐edged sword?

The sudden outbreak of SARS‐CoV‐2‐infected disease (COVID‐19), initiated from Wuhan, China, has rapidly grown into a global pandemic. Emerging evidence has implicated extracellular vesicles (EVs), a key intercellular communicator, in the pathogenesis and treatment of COVID‐19. In the pathogenesis of COVID‐19, cells that express ACE2 and CD9 can transfer these viral receptors to other cells via EVs, making recipient cells more susceptible for SARS‐CoV‐2 infection. Once infected, cells release EVs packaged with viral particles that further facilitate viral spreading and immune evasion, aggravating COVID‐19 and its complications. In contrast, EVs derived from stem cells, especially mesenchymal stromal/stem cells, alleviate severe inflammation (cytokine storm) and repair damaged lung cells in COVID‐19 by delivery of anti‐inflammatory molecules. These therapeutic beneficial EVs can also be engineered into drug delivery platforms or vaccines to fight against COVID‐19. Therefore, EVs from diverse sources exhibit distinct effects in regulating viral infection, immune response, and tissue damage/repair, functioning as a double‐edged sword in COVID‐19. Here, we summarize the recent progress in understanding the pathological roles of EVs in COVID‐19. A comprehensive discussion of the therapeutic effects/potentials of EVs is also provided. Extracellular vesicles (EVs) are a novel mediator of COVID‐19 pathogenesis/treatment. EVs facilitate viral spreading via transferring viral particles and receptors to recipient cells. Stem cell‐derived EVs can be used as therapeutic “drug” to treatment COVID‐19 or drug delivery platform to fight against COVID‐19.