SARS-CoV-2 targets glial cells in human cortical organoids

Stem Cell Reports. 2021 May 11;16(5):1156-1164. doi: 10.1016/j.stemcr.2021.01.016.

Abstract

Coronavirus disease 2019 (COVID-19) patients have manifested a variety of neurological complications, and there is still much to reveal regarding the neurotropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human stem cell-derived brain organoids offer a valuable in vitro approach to study the cellular effects of SARS-CoV-2 on the brain. Here we used human embryonic stem cell-derived cortical organoids to investigate whether SARS-CoV-2 could infect brain tissue in vitro and found that cortical organoids could be infected at low viral titers and within 6 h. Importantly, we show that glial cells and cells of the choroid plexus were preferentially targeted in our model, but not neurons. Interestingly, we also found expression of angiotensin-converting enzyme 2 in SARS-CoV-2 infected cells; however, viral replication and cell death involving DNA fragmentation does not occur. We believe that our model is a tractable platform to study the cellular effects of SARS-CoV-2 infection in brain tissue.

Keywords: COVID-19; SARS-CoV-2; cortical organoid; glial cells; human embryonic stem cells; neurological symptoms; neurotropism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / pathology*
  • Cells, Cultured
  • Choroid Plexus / cytology
  • Choroid Plexus / pathology*
  • Choroid Plexus / virology
  • Human Embryonic Stem Cells / cytology*
  • Humans
  • Neuroglia / pathology
  • Neuroglia / virology*
  • Neurons / virology
  • Organoids / cytology
  • Organoids / innervation*
  • Organoids / pathology*
  • SARS-CoV-2 / pathogenicity