SARS-CoV-2 infects neurons in vitro

July 13, 2020 by Sam Bazzi

A study published recently in ALTEX demonstrates that the SARS-CoV-2 virus can invade neurons expressing the ACE2 receptor using a BrainSphere in vitro model. BrainSpheres are essentially tiny models of the brain that are produced from human inducible pluripotent stem cells (iPSCs). These cells can differentiate into neurons, astrocytes, and oligodendrocytes to form a 3D co-culture. These cultures have the potential for being standardized and mass-produced, which make them a very useful model to study neural processes. The authors of this study utilized BrainSpheres to study the neuroinvasive potential of the SARS-CoV-2 virus, which has been widely hypothesized but until now had not been definitively shown in vitro. BrainSpheres were cultured and analyzed for expression of ACE2 and TMPRSS2 in both fully formed BrainSpheres and neuroprogenitor cells (NPCs, used to generate BrainSpheres). The authors found that both NPCs and BrainSpheres expressed ACE2 but not TMPRSS2, two cell surface proteins utilized by SARS-CoV-2 for cellular entry and spike protein priming, respectively. The authors found that the virus was still able to infect a small fraction of neurons at 72 hours post-infection (hpi). Of note, they also found that SARS-CoV-2 RNA levels were markedly higher at 72 hpi compared to 6 hpi, indicating that the virus could replicate in neurons. The cultures were washed extensively before lysing the BrainSpheres to ensure that none of the initial viral inoculum was altering viral detection within the cells.

Many have hypothesized that due to high prevalence of neurological symptoms in COVID-19 (in some studies up to 40-50% of patients), there may be neuroinvasive potential by SARS-CoV-2 – but this is the first report showing that the virus can actually replicate within neurons. The implication of these findings is quite stunning because although some human coronaviruses such as the 229E and OC43 strains have already been shown to be neurotropic (see blog post 5/4/2020), SARS-CoV-2’s potential neurotropism may be directly related to neurological symptoms. Additionally, these coronavirus strains have been hypothesized as potential risk factors for autoimmune disorders such as MS. If SARS-CoV-2 is demonstrated to be neurotropic in humans, it would be interesting to study any correlation between COVID-19 and autoimmune disorders.

Written by: Sam Bazzi
Edited by: Jina Zhou and Esther Melamed
7/13/2020