3D ‘assembloid’ shows how SARS-CoV-2 infects brain cells

New York: A team of researchers has produced a stem cell model that demonstrates a potential entry route for SARS-CoV-2, the virus that causes Covid-19, into the human brain.

Results published in the journal Nature Medicine indicate that a potential pathway for SARS-CoV-2 in the brain is through blood vessels, where SARS-CoV-2 can infect pericytes, and then SARS-CoV-2 can seep. spread to other types of brain cells.

“Clinical and epidemiological observations suggest that the brain may be involved in infection with SARS-CoV-2,” said lead author Joseph Gleeson of the University of California at San Diego.

“The prospect of Covid-19-induced brain damage has become a major concern in ‘long COVID’ cases, but cultured human neurons are not susceptible to infection. Previous publications suggested that the cells that make cerebrospinal fluid could be infected with SARS-CoV-2, but other routes of entry seemed likely, ”Gleeson added.

The team confirmed that human neural cells are resistant to infection with SARS-CoV-2. However, recent studies have suggested that other types of brain cells could serve as a “Trojan horse.”

Pericytes are specialized cells that wrap around blood vessels and carry the SARS-CoV-2 receptor.

Researchers introduced pericytes into cultures of three-dimensional neural cells – 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 exhibited robust infection with SARS-CoV-2.

The coronavirus was able to infect the pericytes, which served as localized factories for the production of SARS-CoV-2. These locally produced SARS-CoV-2 could then spread to other cell types, causing widespread damage.

With this improved model system, they found that supporting cells called astrocytes were the primary target of this secondary infection.

“Alternatively, infected pericytes could lead to inflammation of the blood vessels, followed by clotting, stroke, or bleeding, complications that are seen in many SARS-CoV-2 patients who are hospitalized in intensive care.