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How Coronavirus attacks the brain

Coronavirus mainly affects the lungs, but also the kidneys, liver and blood vessels. However, around half of patients report neurological symptoms, including headaches, confusion, and delirium, suggesting the virus may also attack the brain.

A new study offers the first clear evidence that coronavirus invades brain cells in some people, hijacking them to make copies of itself. The virus also appears to suck up all nearby oxygen, starving nearby cells.

It is not clear how the virus gets to the brain or how often it unleashes this trail of destruction. Brain infection is likely to be rare, but some people may be susceptible due to their genetic background, high viral load, or other reasons.

“If the brain becomes infected, it could have a lethal consequence,” said Akiko Iwasaki, a Yale University immunologist who led the work.

The study went online Wednesday and has not yet been reviewed by experts for publication. But several researchers said he was careful and elegant, showing in several ways that the virus can infect brain cells.

Scientists had to rely on brain imaging and patient symptoms to infer the effects on the brain, but “we didn’t really see much evidence that the virus could infect the brain, even though we knew it was a potential possibility,” he said. dr. Michael Zandi, consultant neurologist at the National Hospital for Neurology and Neurosurgery in Great Britain. “These data provide just a little more evidence than they certainly can.”

Dr. Zandi and his colleagues Research published in July showing that some patients with Covid-19, the disease caused by the coronavirus, develop serious neurological complications, including nerve damage.

In the new study, Dr. Iwasaki and her colleagues documented brain infection in three ways: in the brain tissue of a person who died of Covid-19, in a mouse model, and in organoids – clusters of brain cells in a laboratory dish intended to mimic the three-dimensional structure of the brain.

Other pathogens, including the Zika virus, are known to infect brain cells. The immune cells then flood the damaged sites, trying to purify the brain by destroying the infected cells.

The coronavirus is much more stealthy: it uses the mechanism of brain cells to multiply, but it doesn’t destroy them. Instead, it chokes oxygen to adjacent cells, causing them to wither and die.

Researchers have found no evidence of an immune response to remedy this problem. “It’s kind of a silent infection,” said Dr. Iwasaki. “This virus has many evasion mechanisms.”

These findings are consistent with other observations on coronavirus-infected organoids, said Alysson Muotri, a neuroscientist at the University of California, San Diego, who also studied the Zika virus.

The coronavirus appears to rapidly decrease the number of synapses, the connections between neurons. “Days after infection, and we already see a drastic reduction in the amount of synapses,” said Dr. Muotri. “We still don’t know if it’s reversible or not.”

The virus infects a cell via a protein on its surface called ACE2. That protein appears throughout the body and especially in the lungs, explaining why they are the preferred targets of the virus.

Previous studies have suggested, based on a proxy for protein levels, that the brain has very little ACE2 and is likely to be spared. But Dr. Iwasaki and her colleagues took a closer look and found that the virus could actually enter brain cells using this gate.

“It is quite clear that it is expressed in neurons and is required for entry,” said Dr. Iwasaki.

His team then examined two series of mice: one with the ACE2 receptor expressed only in the brain and the other with the receptor only in the lungs. When they introduced the virus into these mice, the brain-infected mice quickly lost weight and died within six days. The lung-infected mice did neither.

Despite the warnings attached to the mouse studies, the findings still suggest that virus infection in the brain may be more lethal than respiratory infection, Dr. Iwasaki said.

The virus can get to the brain through the olfactory bulb – which regulates smell – through the eyes or even from the bloodstream. It is unclear which path the pathogen is taking and whether it does so often enough to explain the symptoms seen in people.

“I think this is a case where the scientific data is ahead of the clinical evidence,” said Dr. Muotri.

Researchers will need to analyze many autopsy samples to estimate how common the brain infection is and whether it is present in people with milder illnesses or in so-called long-range vehicles, many of which have a myriad of neurological symptoms.

40-60% of patients with Covid-19 have neurological and psychiatric symptoms, said Dr. Robert Stevens, a neurologist at Johns Hopkins University. But the symptoms may not all stem from the virus invading brain cells. They can be the result of pervasive inflammation throughout the body.

For example, inflammation in the lungs can release molecules that make blood sticky and clog blood vessels, resulting in strokes. “The brain cells themselves don’t need to be infected for that to happen,” said Dr. Zandi.

But in some people, he added, it may be a low level of oxygen in the blood from infected brain cells that triggers stroke: “Different groups of patients can be affected in different ways,” he said. “It is entirely possible that you will see a combination of both.”

Some cognitive symptoms, such as brain fog and delirium, may be more difficult to detect in sedated and ventilated patients. Doctors should plan to reduce sedatives once a day if possible in order to evaluate patients with Covid-19, Dr Stevens said.

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