Confusion and delirium: scientists have figured out how COVID-19 attacks the brain

Scientists have reported that the coronavirus does not only affect the lungs - the pathogen can penetrate brain cells, causing symptoms such as delirium and confusion. Writes about this The New York Times.

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The coronavirus primarily affects the lungs, but also the kidneys, liver and blood vessels. However, about half of patients report neurological symptoms, including headaches, confusion, and delirium. This gives scientists reason to believe that the virus can also attack the brain.

The new study offers the first clear evidence that in some people, the coronavirus invades brain cells, capturing them to make copies of itself. In this case, the virus absorbs all the oxygen in the vicinity, killing adjacent brain cells.

It is unclear how the virus enters the brain and how often it leaves this destructive trail. Infection of the brain with this virus is rare, given the available evidence. But some people may be more susceptible to this threat due to genetic background, high viral load, or other reasons.

“If the brain is truly infected, it could have lethal consequences,” said Akiko Iwasaki, an immunologist at Yale University who led the study.

The study was posted online and has not yet been reviewed by experts. But several researchers said it was neat and elegant, proving in many ways that the virus can actually infect brain cells.

Scientists have previously compared brain images and patient symptoms to infer the effects of the new coronavirus on the brain, but "we really didn't see a lot of evidence that the virus could infect the brain, although we knew it was a potential possibility," said Dr. Michael Zandi. Consultant neurologist at the UK National Hospital for Neurology and Neurosurgery. “The data from the new study provides a little more evidence that this is definitely possible.”

In July, Dr. Zandi and colleagues published a study showing that some patients with COVID-19 develop serious neurological complications, including nerve damage.

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In a new study, Dr. Iwasaki and her colleagues documented brain infection in three ways: in brain tissue from a person who died from COVID-19; in a mouse model; and in organoids—clusters of brain cells in a laboratory environment that mimic the three-dimensional structure of the brain.

Other pathogens, including the Zika virus, are known to infect brain cells. Immune cells then flood the damaged areas in an attempt to cleanse the brain by destroying the infected cells.

The coronavirus is much more secretive: it uses the mechanisms of brain cells to reproduce, but does not destroy them. Instead, it cuts off oxygen to neighboring cells, causing them to wither and die.

Researchers have not found any evidence of an immune response that can address this problem.

“It’s kind of a silent infection,” Dr. Iwasaki said. “This virus has many evasion mechanisms.”

These results are consistent with other observations of organelles infected with the coronavirus, said Elysson Muotri, a neuroscientist at the University of California, San Diego, who also studied the Zika virus.

The coronavirus seems to be rapidly decreasing the number of synapses, connections between neurons.

“Within a few days of infection, we can already see a dramatic reduction in the number of synapses,” Dr. Muotri said. “We don’t know yet whether it’s reversible or not.”

The virus infects a cell through a protein on its surface called ACE2. This protein is found throughout the body, especially in the lungs, which explains why they are preferred targets for the virus.

Previous research has suggested, based on indirect indicators of protein levels, that there is very little ACE2 in the brain. But Dr. Iwasaki and her colleagues took a closer look and found that the virus can indeed enter brain cells.

Her team then studied two groups of mice: one that expressed the ACE2 receptor only in the brain, and one that expressed it only in the lungs. When the researchers injected the virus, the mice whose brains were infected quickly lost weight and died within six days. The mice that had infected lungs did not die.

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The results show that a viral infection in the brain can be more deadly than a respiratory infection.

The virus can enter the brain through the olfactory bulb, which regulates odor, through the eyes, or even through the bloodstream. It is unclear which path the pathogen is taking.

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

Researchers will need to analyze multiple autopsy samples from COVID-19 patients to assess how common the brain infection is and whether it is present in people with milder forms of the disease.

According to Dr. Robert Stevens, a neurologist at Johns Hopkins University, 40 to 60 percent of hospitalized COVID-19 patients experience neurological and psychiatric symptoms. But not all symptoms can be caused by a virus invading brain cells. They can be the result of extensive inflammation throughout the body.

For example, inflammation in the lungs can release molecules that block up blood vessels, leading to strokes.

“You don't have to infect the brain cells themselves to do this,” Dr. Zandi said.

But in some people, low oxygen levels in the blood due to infected brain cells can cause a stroke.

“Different patient groups may experience the disease differently,” he said. “It’s entirely possible that you’ll see both.”

Certain cognitive symptoms, such as blurred consciousness and delirium, may be more difficult to detect in patients undergoing sedation and on a ventilator.

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