Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus

Viruses. 2020 Sep 8;12(9):1004. doi: 10.3390/v12091004.


Since the global outbreak of SARS-CoV-2 (COVID-19), infections of diverse human organs along with multiple symptoms continue to be reported. However, the susceptibility of the brain to SARS-CoV-2, and the mechanisms underlying neurological infection are still elusive. Here, we utilized human embryonic stem cell-derived brain organoids and monolayer cortical neurons to investigate infection of brain with pseudotyped SARS-CoV-2 viral particles. Spike-containing SARS-CoV-2 pseudovirus infected neural layers within brain organoids. The expression of ACE2, a host cell receptor for SARS-CoV-2, was sustained during the development of brain organoids, especially in the somas of mature neurons, while remaining rare in neural stem cells. However, pseudotyped SARS-CoV-2 was observed in the axon of neurons, which lack ACE2. Neural infectivity of SARS-CoV-2 pseudovirus did not increase in proportion to viral load, but only 10% of neurons were infected. Our findings demonstrate that brain organoids provide a useful model for investigating SARS-CoV-2 entry into the human brain and elucidating the susceptibility of the brain to SARS-CoV-2.

Keywords: ACE2; SARS-CoV-2; brain organoid; cortical neuron; pseudovirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Axons / enzymology
  • Betacoronavirus / physiology*
  • Cell Differentiation
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Embryonic Stem Cells / virology
  • HEK293 Cells
  • Humans
  • Nerve Tissue Proteins / physiology
  • Neural Stem Cells / enzymology
  • Neural Stem Cells / virology
  • Neurons / enzymology
  • Neurons / virology*
  • Organoids / virology*
  • Peptidyl-Dipeptidase A / physiology
  • Prosencephalon / cytology
  • Prosencephalon / virology*
  • Receptors, Virus / physiology
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / physiology*
  • Viral Load
  • Viral Tropism
  • Virus Internalization


  • Nerve Tissue Proteins
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2