A team of researchers has produced a stem cell model that demonstrates a potential route of entry of SARS-CoV-2, the virus that causes Covid-19, into the human brain.
The findings published in the journal Nature Medicine, indicate that one potential route of SARS-CoV-2 into the brain is through the blood vessels, where SARS-CoV-2 can infect pericytes and then SARS-CoV-2 can spread to other types of brain cells.
“Clinical and epidemiological observations suggest that the brain can become involved in SARS-CoV-2 infection,” said senior author Joseph Gleeson from the University of California San Diego.
“The prospect of Covid-19-induced brain damage has become a primary concern in cases of ‘long COVID,’ but human neurons in culture are not susceptible to infection. Prior publications suggest that the cells that make the spinal fluid could become infected with SARS-CoV-2, but other routes of entry seemed likely,” Gleeson added.
The team confirmed that human neural cells are resistant to SARS-CoV-2 infection. However, recent studies hinted that other types of brain cells might serve as a ‘Trojan horse.’
Pericytes are specialised cells that wrap around blood vessels — and carry the SARS-CoV-2 receptor.
The researchers introduced pericytes into three-dimensional neural cell cultures — brain organoids — to create “assembloids” — a more sophisticated stem cell model of the human body.
These assembloids contained many types of brain cells in addition to pericytes, and showed robust infection by SARS-CoV-2.
The coronavirus was able to infect the pericytes, which served as localised factories for the production of SARS-CoV-2. These locally produced SARS-CoV-2 could then spread to other cell types, leading to widespread damage.
With this improved model system, they found that the supporting cells known as astrocytes were the main target of this secondary infection.
“Alternatively, the infected pericytes could lead to inflammation of the blood vessels, followed by clotting, stroke or hemorrhages, complications that are observed in many patients with SARS-CoV-2 who are hospitalised in intensive care units,” Gleeson noted.