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

Immunology. 2021 Aug;163(4):416-430. doi: 10.1111/imm.13329. Epub 2021 May 4.

Abstract

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.

Keywords: COVID-19; Cytokine storm; Extracellular vesicle; Inflammation; SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage
  • COVID-19 / immunology
  • COVID-19 / metabolism
  • COVID-19 / therapy
  • COVID-19 / virology*
  • COVID-19 Drug Treatment
  • COVID-19 Vaccines / administration & dosage
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / metabolism
  • Cytokine Release Syndrome / virology
  • Cytokines / metabolism
  • Drug Carriers
  • Extracellular Vesicles / immunology
  • Extracellular Vesicles / metabolism
  • Extracellular Vesicles / transplantation
  • Extracellular Vesicles / virology*
  • Host-Pathogen Interactions
  • Humans
  • Inflammation Mediators / metabolism
  • Lung / immunology
  • Lung / metabolism
  • Lung / virology*
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / metabolism*
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity*
  • Virion / immunology
  • Virion / metabolism*

Substances

  • Antiviral Agents
  • COVID-19 Vaccines
  • Cytokines
  • Drug Carriers
  • Inflammation Mediators