According to new research, the coronavirus that causes COVID-19 can hijack brain cells by copying itself using the internal mechanisms of the cell.
The study was posted to the preprint database on September 8th. bioRxivAlthough not yet published in peer-reviewed journals, it provides evidence that SARS-CoV-2 can directly infect brain cells called neurons. Coronavirus is associated with various forms of brain injury, Fatal inflammation To a brain disorder known as EncephalopathyAll of this can cause confusion, fog in the brain, delirium, and so far there has been little evidence that the virus itself has invaded brain tissue.
“We are actively examining the tissues of more patients so that we can find such frequencies. brain Akiko Iwasaki, a senior author who is an immunologist at Yale University, told Live Science by email. In addition, scientists need to figure out how the virus invades the virus, and whether it can be moved away from the brain in the first place, the authors said in their report.
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Human, mouse, mini brain
To see if SARS-CoV-2 can invade brain cells, the study authors examined the autopsy brain tissue of three patients who died of COVID-19. They also experimented with COVID-19-infected mice and organoids-a group of cells grown in a laboratory dish to mimic the 3D structure of brain tissue.
“This is the first study to perform an extensive analysis of SARS-CoV-2. [brain] “Infection using three models,” said Dr. Maria Nagel, a professor of neurology and ophthalmology at the University of Colorado School of Medicine who was not involved in the study. Previously, there was only a “rare case report” of SARS-CoV-. 2 RNA The virus particles found in the post-mortem tissue of a patient specializing in neurovirology were also emailed to Live Science.
On organoids, the team discovered that the virus could invade neurons via the ACE2 receptor, a protein on the cell surface. Virus It is used to enter cells and induce infection. The inside of the infected cell was then examined using an electron microscope that illuminates the tissue with a beam of charged particles. They could see Corona virus Intracellular “germinating” particles indicate that the virus has directed the internal mechanisms of the neuron to build a new copy of itself.
The virus also caused metabolic changes in nearby uninfected neurons while it set up stores in infected cells. The cells near these are killed in large numbers, suggesting that infected cells may steal oxygen from neighboring cells in order to continue producing new viruses, the authors said.
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“I don’t know if similar events are happening in infected people,” Iwasaki points out. In autopsy tissue, the team found that SARS-CoV-2 had infected several neurons in the wrinkled cerebral cortex. Near these infected cells, they found evidence that a “small stroke” had occurred, implying that the virus, like organoids, might steal oxygen from cells near the brain, Iwasaki said. ..
In particular, as expected, the infected brain tissue was not flooded with immune cells. When Zika virus Or when the rabies virus invades the brain, it is usually followed by a large number of immune cells, the authors said. Therefore, successful infiltration of SARS-CoV-2 into the brain may somehow evade the body’s typical defenses against such invasion. It is not yet known how this abnormal immune response affects the course of infection, but removing the virus from the brain can be even more difficult. The authors also state that while few immune cells collect at the site of infection, nearby dying neurons can cause a chain reaction in the nervous system, causing harmful inflammation.
Finally, in a mouse experiment, the authors genetically modified one group of mice to express the human ACE2 receptor in the brain, while another group of mice had only the receptor in the lungs. The first set of mice began to lose weight rapidly and died within 6 days, while the second set of mice did not lose weight and survived. In addition, in brain-infected mice, the placement of blood vessels in the brain changed dramatically, presumably redirecting nutrient-rich blood to “metabolically active hotspots” that the virus hijacked, the authors write. There is.
Next step
Studies of organoids and mice provide hints on how SARS-CoV-2 is lethal when it reaches the brain. But now scientists need to see if the same results are passed on to humans.
“All systems have their limits,” Iwasaki points out. For example, COVID-19 infection can progress in mice differently than in humans, and organoids resemble mini-brain but do not contain blood vessels such as immune cells or full-scale organs. ..
“In humans, the virus is not directly introduced into the brain,” Nagel said, as in mouse experiments. Scientists need to further examine the autopsy tissue of COVID-19 patients to determine if the results of this preliminary work can be tolerated by a larger group of people.
Due to the limited supply of human brain tissue, non-human primates infected with SARS-CoV-2 may also serve as a research model, Nagel said.
“The virus may be present in certain brain regions or have an indirect effect on nerve function,” Nagel added. In particular, some patients Chronic fatigue syndrome It has been several months since the first COVID-19 infection became established. She said the syndrome has been suggested to result from changes in hormonal function regulated by specific parts of the brain. Another important question, she said, is “whether the virus affects the respiratory center of the brainstem-whether it contributes to respiratory failure in patients with severe COVID.”
In addition, scientists still need to first understand how the virus sneaks into the brain.
When scientists learn that COVID-19 can disrupt the abilities of people with odors and tastes, some may infect the brain directly by the virus moving through the nerves of the nose. I theorized that I couldn’t Previously reported live science.. Iwasaki agrees that the virus can enter the brain through the nose. Alternatively, it can enter through the bloodstream through the impaired area of the blood-brain barrier, which is usually the wall of tissue that separates brain tissue from circulating blood and allows only certain substances to pass through. Knowing the route by which the virus reaches the brain is key to the prevention and treatment of infections, the authors said.
Originally published in Live Science.
