According to a new study, the cornivirus that causes COVID-19 can sometimes hijack brain cells, using the cells’ internal machinery.
The research, posted to the printprint database on 8 September bioRxiv, Has not yet been published in a peer-reviewed journal, but provides evidence that SARS-CoV-2 can directly infect brain cells called neurons. Although coronovirus has been linked to various forms of brain damage Malignant inflammation Known as brain diseases encephalopathies, All of which can cause confusion, brain fog and delirium, there was little evidence of the virus attacking the brain tissue so far.
“We are actively looking at more patient tissues to find out how often this happens Brain Infection occurs … and what symptoms are related to which areas of the brain are infected, “senior author Akiko Iwasaki, an immunologist at Yale University, told Live Science in an email. In addition, scientists still know this It should be determined how the virus enters. The brain in the first place, and whether it can be excluded from the brain, the authors noted in their report.
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Human, mouse and mini-brains
To see if SARS-CoV-2 can break down in brain cells, the study authors examined the brain tissue of three patients who died of COVID-19. He also conducted experiments in mice infected with COVID-19 and in organoids – groups of cells developed in a laboratory dish to mimic the 3D structure of brain tissue.
“This study is the first to conduct a comprehensive analysis of SARS-COV-2 [brain] Infection using three models, “said Dr. Maria Nagle, a professor of neurology and ophthalmology at the University of Colorado School of Medicine, who was not involved in the study. Previously, there were only” rare case reports “of SARS-COV. 2 RNA and viral particles were found in postmortem tissue from patients, Nagel, who specializes in neurovirology, told Live Science in an email.
In organoids, the team found that the virus could enter neurons via the ACE2 receptor, a protein on the cell surface that Virus Uses to enter the cell and trigger infection. They then used an electron microscope, which uses a beam of charged particles to illuminate the tissue to peer inside the infected cells. They could see Coronavirus “Budding” within the particle cell, showing that the virus had commanded the internal machinery of neurons to make new copies of itself.
While establishing shop in infected cells, the virus also caused metabolic changes in nearby neurons, which were not infected. The authors noted that these cells died in large numbers, suggesting that infected cells could steal oxygen from their neighbors to produce new viruses.
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“We do not know whether similar incidents are occurring in infected people,” Iwasaki said, although there is some evidence. In autopsied tissue, the team found that SARS-CoV-2 infected some neurons in the wrinkled cerebral cortex. Near these infected cells, they found evidence of having “small strokes”, indicating that the virus could steal oxygen from nearby cells in the brain, as it did in organoids, Iwasaki said.
Notably, infected brain tissue was not filled with immune cells, as might be expected. when Zika virus Or as the rabies virus attacks the brain, a large number of immune cells usually follow, the authors noted. It is therefore possible that when SARS-CoV-2 infiltrates the brain, it may evade the body’s specific defense against any kind of invasion. It is not yet known how this abnormal immune response may affect the course of the infection, but it may make the virus more difficult to clear from the brain. Although some immune cells are ejaculated at the site of infection, neurons that die nearby may trigger a chain-reaction in the nervous system that still leads to deleterious inflammation, the authors noted.
Finally, in mouse experiments, the authors genetically modified a group of mice to express human ACE2 receptors in their brains, while another group of mice only bore the receptor in their lungs. The first set of mice lost weight rapidly and died within six days, while the second set did not lose weight and survived. Furthermore, in mice with brain infections, the arrangement of blood vessels in the brain changes dramatically, possibly due to nutrient-rich blood in the “metabolically active hot spots” where the virus has taken over, the authors said. Wrote
Organoid and mouse studies indicate how malignant SARS-COV-2 can occur when it reaches the brain. But now, scientists should see if the same results lead to humans.
Iwasaki said, “Every experimental system has its limits.” For example, COVID-19 infection can progress differently in mice than in humans, and while somewhat resembling a mini-brain, they do not contain full-sized organs such as immune cells or blood vessels, he said.
In addition, “in humans, the virus is not directly introduced into the brain” as in mouse experiments, Nagel said. Scientists will need to examine more autopsy tissue from COVID-19 patients to determine if the findings of this preliminary work are in larger groups of people.
Nagle stated that non-nonhuman primates infected with SARS-COV-2 may also serve as research models, as the supply of human brain tissue is limited.
“The virus may be present in specific brain regions or have a more indirect effect on neurological function,” Nagle said. In particular, some patients are reminiscent of symptoms chronic fatigue syndrome Until months after their initial COVID-19 infection; It has been suggested that the syndrome arises from changes in hormone function regulated by specific parts of the brain, he notes. Another important question is that “the virus affects the respiratory center in the brain – contributing to respiratory failure in critically ill COVID patients,” she said.
What’s more, scientists still need to find out how the virus penetrates the brain in the first place.
When scientists discovered that COVID-19 can inhibit people’s ability to smell and taste, some believe that the virus can infect the brain by traveling through veins directly into the nose, Live science first told. The virus can invade the brain through the nose, Iwasaki agreed, or it can enter through the bloodstream by crossing compromised areas of the blood-brain barrier – a wall of tissue that typically enters the brain tissue Separates the blood from circulating and passes only through certain channels. The authors mentioned that learning which pathways the virus goes through in the brain will be important in preventing and treating the infection.
Originally published on Live Science.