Using lab-grown ‘mini brains,’ scientists show SARS-CoV-2 may infect brain cells directly

BALTIMORE — Believe it or not, scientists have not yet zoned in on the full range of symptoms COVID-19 can cause. Early reports from Wuhan, China show that more than a third of coronavirus patients (36%) exhibit neurological symptoms. It’s remained unclear if the virus infects brain cells, or if these symptoms are the byproduct of other things going on in the body. Using “miniature brains” created in their laboratories, Johns Hopkins scientists now show that the SARS-CoV-2 virus can infect brain cells directly.

These futuristic mini brains are a type of organoid — a tissue culture grown from human cells that simulates an organ. Researchers think the coronavirus might be able to infect brain cells because some cells express the receptor ACE2. Previous research has shown that ACE2 is a receptor protein which creates an entryway for the SARS-CoV-2 virus into the lungs. Researchers guessed the coronavirus might use this pathway in the brain as well.

Can SARS-CoV-2 pass the blood brain barrier?

It’s usually quite difficult for the brain to get infected since it has a special line of defense called the “blood brain barrier.” This layer of protection serves to shield the brain from many viruses and bacteria.

'Mini-brain' bioengineered from human stem cells
‘Mini-brain’ bioengineered from human stem cells. The ball is about one third of a millimeter and contains about 30,000 cells. The cell nuclei are blue. The SARS-CoV-2 virus is stained red, indicating that a small fraction of brain cells carries a large number of virus particles. This means that virus has multiplied in infected cells. (Image credit: Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health)

“Whether or not the SARS-CoV-2 virus passes this barrier has yet to be shown,” explains senior author Thomas Hartung, M.D., Ph.D., chair for evidence-based toxicology at the Bloomberg School of Public Health at Hopkins, in a press release. “However, it is known that severe inflammations, such as those observed in COVID-19 patients, make the barrier disintegrate.”

When researchers introduced the SARS-CoV-2 to the mini brains, the virus was able to pass the blood brain barrier and infect the brains directly.

Warning for pregnant women

The authors note one big implication from the results of their experiments for women. During its earliest stages of development, the brain lacks a functional blood brain barrier, and the ACE2 receptor is already present in some cells. Extra precautions should be taken during pregnancy to prevent infection of the embryo.

“This study is another important step in our understanding of how infection leads to symptoms, and where we might tackle the COVID-19 disease with drug treatment,” concludes Dr. William Bishai, a professor of medicine at the Johns Hopkins University School of Medicine, and leader of the infectious disease team for the study.

The study is published in Altex: Alternatives to Animal Experimentation.

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