UCSD researchers help show how coronavirus infects brain cells

Researchers from the UC San Diego School of Medicine and Rady Children’s Institute for Genomic Medicine say they have produced a stem cell model showing a potential entry route for the COVID-19 coronavirus into the human brain.

The findings were published in the July 9 online issue of Nature Medicine.

“Clinical and epidemiological observations suggest that the brain can become involved in SARS-CoV-2 infection,” said Dr. Joseph Gleeson, research senior author and a neuroscience professor at the UCSD School of Medicine.

“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,” said Gleeson, who also is neuroscience research director at the Rady Children’s Institute for Genomic Medicine. “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 and his colleagues, including neuroscientists and infectious-disease specialists, confirmed that human neural cells are resistant to SARS-CoV-2 infection. At the same time, recent studies hinted that other types of brain cells might serve as a “Trojan horse.”

According to the findings, pericytes — specialized cells that wrap around blood vessels — carry the SARS-CoV-2 receptor.

Researchers introduced pericytes into three-dimensional neural cell cultures to create “assembloids,” or a more sophisticated stem cell model of the human body.

The assembloids contained many types of brain cells along with pericytes and showed “robust infection” by SARS-CoV-2.

The coronavirus was able to infect the pericytes, which served as localized factories for production of SARS-CoV-2, according to the researchers.

In turn, the locally produced SARS-CoV-2 could then spread to other cell types, leading to widespread damage.

Gleeson said the results indicate that one potential route of SARS-CoV-2 into the brain is through blood vessels, where the virus can infect pericytes and then spread to other types of brain cells.

“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 hospitalized in intensive care units,” Gleeson said.

Researchers said they now plan to focus on developing improved assembloids that contain pericytes and blood vessels capable of pumping blood to better model the brain.

Gleeson added that these models could provide greater insight into infectious diseases and other brain disease. ◆