The tiny blobs of brain tissue that Thomas Hartung grows in his lab at Johns Hopkins University aren’t much to look at. Just barely visible, they are little more than squishy white specks.

Known as “mini brains,” or organoids, these minuscule structures made from stem cells contain neurons that spontaneously emit electrical activity as a real brain would. The ones Hartung grows resemble the brain of a human fetus at five months of development.

Hartung and his team are using the brain organoids to better understand SARS-CoV-2, the virus that causes Covid-19. What they’ve found so far about the brain’s susceptibility to the virus is concerning: “It’s bad news adding to a pile of bad news,” Hartung tells OneZero.

Scientists have been growing organoids for over a decade, but the current pandemic has led to a flurry of interest in using them to study the new coronavirus. Researchers are now conducting similar tests with miniature lungs, guts, and livers, as well as rubbery “organs-on-chips.”

There’s a lot scientists still don’t know about the virus, and lab animals can only tell us so much. Since many animals don’t get Covid-19 like people do, human mini organs offer a way to learn which cells the virus can infect and how infection damages the body. Plus, organoids are a faster and cheaper option than using research animals because they can be mass-produced by the hundreds or thousands in the lab. Scientists are also using mini organs as stand-ins for real ones to test potential drugs to treat Covid-19.

Before Covid-19, brain organoids helped unravel another viral mystery: why some pregnant women who got infected with the Zika virus gave birth to babies with smaller brains and heads. When scientists exposed mini brains to Zika, they found that still-developing neurons were especially susceptible to the virus.

After Hartung and his colleagues read reports of some Covid-19 patients experiencing neurological symptoms in addition to respiratory ones, they wanted to know whether SARS-CoV-2 could infect brain cells, too.

It was the job of C. Korin Bullen, a postdoctoral researcher at Johns Hopkins Medicine, to find out. To work with the dangerous live virus, she donned a protective suit, shoe covers, gloves taped at the wrists, and a hooded face shield. She then entered a biosafety lab, where she exposed the brain organoids to the coronavirus.

What she found was that the virus could infect the mini brains and, 72 hours later, it began multiplying inside them, suggesting that human brain cells are susceptible to the virus. The results were published online June 26 in the journal ALTEX: Alternatives to Animal Experimentation.

“This means the virus has the potential to infect human brain cells, which is very much in line with the many neurological symptoms seen in patients,” Hartung says.

In the _Journal of the American Medical Association _on April 10, Chinese researchers reported that about 36% of 214 Covid-19 patients at a Wuhan hospital had neurological symptoms in addition to respiratory ones. And a study published July 8 in the journal Brain found that neurological complications of Covid-19 can include delirium, brain inflammation, stroke, and nerve damage.

It’s not yet known how the virus causes these symptoms. It’s possible that SARS-CoV-2 can cross or at least weaken the blood-brain barrier, the protective border meant to keep toxins and pathogens out of the brain. Organoids lack this barrier, so Hartung and his team couldn’t test the virus’s ability to penetrate it. But if the virus can affect the brain, it could have implications for drug development. To effectively treat Covid-19 patients with neurological symptoms, Hartung says you might need a drug that can pass through the blood-brain barrier. Not all drugs can.

The Johns Hopkins study also raises concerns for pregnant women. Like real human brains, the mini brains contain the same receptor, called ACE2, that allows the virus to enter lung cells. While there’s no evidence yet that the virus causes miscarriage, birth defects, or developmental disorders, Hartung says the possibility can’t be ruled out yet.

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What Miniature Lab-Grown Brains Reveal About the Effects of Covid-19
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