- The Washington Times - Wednesday, July 1, 2020

Researchers from Johns Hopkins University using “mini-brains” made from human stem cells have discovered that brain cells could be infected by the coronavirus, an indication that COVID-19 could cause serious neurological problems.

Virologists, neuro toxicologists and infectious disease experts from the university introduced SARS-CoV-2 particles into the mini-brains, which model the growing human brain, and found what they believe is the first evidence of the pathogen infecting cells and replicating.

“What we don’t know at the moment is which cells are infected. Is it a very specific subpopulation or is it just random?” said Dr. Thomas Hartung, the study’s senior author and chairman for evidence-based toxicology at Hopkins’ Bloomberg School of Public Health. “Because we only see only a very few cells are infected with our low starting dose of virus particles We also don’t know if this is leading to a type of chronic infection.”

Earlier reports from Wuhan, China, where the COVID-19 pandemic began, suggest that 36% of infected patients experienced neurological symptoms such as impaired consciousness and dizziness. However, it has been unclear whether the virus can infect human brain cells.

Using organoids (tiny tissue cultures made from human cells that simulate entire organs), Hopkins researchers show that certain neurons express an ACE2 receptor, the same one the coronavirus uses to enter the lungs. They conclude that ACE2 offers a way to the brain in their study, which was published last week in the journal ALTEX: Alternatives to Animal Experimentation.

While the blood-brain barrier protects the brain from many viruses, it is unknown whether the coronavirus can break through, Dr. Hartung noted. But he said severe inflammation such as that observed in COVID-19 patients can weaken the barrier.

He described the brain as being “immunoprivileged,” which means the immune system does all it can to spare that organ from its defenses. But it also means it is impossible for the immune system to get rid of brain infections. For example, doctors can remove HIV from almost the entire body except the brain, Dr. Hartung said.

“We could very well be in a situation where there’s a chronic brain infection with coronavirus,” he said. “It means this might impact a new generation of diseases like Alzheimer’s.”

Another concern with SARS-CoV-2 is the effect of the virus on the developing brain. Researchers from Paris-Saclay University found that the virus can cross the placenta in pregnant women, a concern since embryos don’t have the blood-brain barrier in early development.

While the Hopkins researchers don’t have evidence showing the virus can cause developmental disorders, Dr. Hartung said the mini-brains contain the ACE2 receptor from their earliest stages of development.

He said there is much more to learn about how the coronavirus could possibly impact the brain, including the neurodevelopment of children born to mothers with COVID-19.

“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,” said Dr. William Bishai, professor of medicine at Hopkins’ School of Medicine and leader of the infectious disease team for the study.

The mini-brain models, called BrainSpheres, were created four years ago at the Bloomberg School of Public Health. They were the first mass produced, “highly standardized” organoids of their kind, and have been used to model numerous diseases such as viral infections from Zika, HIV and dengue, according to a university press release.

• Shen Wu Tan can be reached at stan@washingtontimes.com.

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