Organoids indicate that SARS-CoV-2 damages the brain barrier

SARS-CoV-2, the virus that causes COVID-19 disease, can disrupt the blood-brain barrier in organoids and damage cells in the choroid plexus, which may lead to long-term neurological complications according to scientists.

While it was previously shown that SARS-CoV-2 can infect brain cells, (see BioNews 1054), in this new work researchers used human pluripotent stem cell-derived brain organoids to simulate the effect of SARS-CoV-2 infection on the human brain.

'It recently became clear that there are neurological symptoms associated with COVID-19 and we have no idea of their long-term implications.' said Dr Laura Pellegrini, lead author of the study. 'We decided to take advantage of our new organoid model to study SARS-CoV-2 entry into the brain, whether the virus can directly infect neuronal cells and its potential implications in the brain barrier damage.'

The scientists at the MRC Laboratory for Molecular Biology in Cambridge found the organoids to be capable of forming a tight barrier similar to the blood-cerebrospinal fluid barrier in the human brain. They observed that mature choroid plexus cells, which produce and secrete cerebrospinal fluid, express ACE2, the cellular protein that SARS-CoV-2 uses to enter the cell. They discovered that the virus was able to infect and produce new viral cells inside the choroid plexus epithelial cells. However, the scientists did not observe infection of neurons or glia cells.

The researchers have also shown that infection with SARS-CoV-2 actually damages the choroid plexus layer because some proteins that usually make up the tight contacts between the cells were mislocalised. This caused brain-barrier leakage, which in humans could enable the entry of pathogens, immune cells and cytokines into cerebrospinal fluid and the brain, and potentially lead to neuroinflammation. This in turn could result in long-term neurological symptoms, such as chronic fatigue and memory loss.

'There is still a lot we don't know about this virus and it's important to continue the basic, fundamental research.' Dr Pellegrini said. The lab is now planning to investigate the biological changes in the choroid plexus after SARS-CoV-2 infection and whether the virus can spread in the cerebrospinal fluid.