Headache, confusion and delirium experienced by some patients with COVID-19 could be the result of coronavirus directly invading the brain, a new study revealed.
According to research, which was led by Yale University immunologist Akiko Iwasaki, the virus is able to replicate within the brain, and its presence deprives nearby brain cells of oxygen, although the prevalence of this is not yet clear.
Other pathogens, such as the Zika virus, are also known to infect brain cells. In this case, immune cells flood damaged places, trying to cleanse the brain by destroying infected cells. However, the SARS-CoV-2 mechanism is different.
How COVID-19 kills the brain
Iwasaki and his colleagues studied the issue in three ways: infecting lab-grown mini-brains known as brain organoids, infecting mice, and examining the brain tissues of COVID-19 patients who had died.
In the organoids of the brain, the team discovered that the SARS-CoV-2 virus is able to infect neurons and then explodes the brain cell machinery to multiply, but does not destroy them. Infected cells, in turn, promote the death of surrounding cells by suffocating their oxygen supply.
The researchers found no evidence of an immune response to remedy this problem.
“It’s kind of a silent infection,” Iwasaki said. “This virus has many evasion mechanisms,” he added.
Finally, they examined the brains of three patients who died from serious complications related to COVID-19 and found evidence of the virus to varying degrees.
Also, infected regions showed no signs of immune cells, such as T cells, precipitating to the site of other viruses such as Zika or herpes to kill infected cells.
How the coronavirus invades the brain
Until now, doctors had believed that neurological impacts seen in about half of all COVID-19 patients could be the result of an abnormal immune response known as a cytokine storm that causes inflammation of the brain rather than a direct invasion of the virus into the brain.
One of the main arguments against the theory of direct invasion of the brain had been that this organ lacks high levels of a protein called ACE2 to which coronavirus clings, and is found in abundance in other organs such as the lungs.
Nonetheless, the team found that the organoids had enough ACE2 to facilitate entry of the virus, and the proteins were also present in the brain tissue of deceased patients.
The team then studied two groups of mice. One of them, genetically altered so that he had ACE2 receptors only in his lungs and the other, only in his brain.
It turned out that the infected mice in his lungs showed some signs of lung injury, while those infected in the brain lost weight quickly and died quickly, which, according to the researchers, indicates potentially higher fatality when the virus enters the brain.
Another proof of their theory is the presence of neutralizing antibodies against the virus in the cerebrospinal fluid of a hospitalized COVID-19 patient suffering from delirium.
Brain infection is likely rare, but some people may be susceptible due to genetic backgrounds, high viral load, or other reasons, they concluded.