The coronavirus that causes COVID-19 can infiltrate star-shaped cells in the brain, causing a chain reaction that can deactivate and even kill the neurons in the environment, according to a new study.
The star-shaped cells, called astrosiete, plays many roles in the nervous system and provides fuel to neurons, which transmit signals through the body and brain. In a laboratory dish, the study found that infected astrocytes stopped producing critical fuel for neurons and secreted an “unidentified” substance that poisoned nearby neurons.
If infected astrocytes do the same in the brain, it could explain the structural changes in patients’ brains, as well as some of the “brain fog” and psychiatric problems apparently associated with some cases of COVID-19, the authors write. wrote.
That said, the new study was placed in the pre-print database on February 7. medRxiv, has not yet been judged by a peer, and an expert told WordsSideKick: ‘this is a lot of preliminary data’ that has yet to be confirmed with additional research, especially regarding the neuronal death that occurs in laboratory dishes.
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“The main message in the newspaper is that the virus is able to get out of there, [into astrocytes], “said study author Daniel Martins-de-Souza, associate professor and head of proteomics at the Department of Biochemistry at the University of Campinas in Brazil.” It does not come there every time, but it does. “
Other studies have found that the coronavirus can also directly infect neurons, although the exact pathway from the virus to the brain is still being investigated. Live Science reported earlier. The new study may add astrocytes long cell that SARS-CoV-2 attacks, but many questions about COVID-19 and the brain remain unanswered, the authors said.
In the brains of COVID-19 patients
The new study drew data from three sources: cells in laboratory dishes, brain tissue from deceased patients, and brain scans from living patients recovering from mild COVID-19 infections.
Given the clear differences between each arm of the study: “I think it is difficult to compare the proportion of mild disease with the serious disease group,” said dr. Maria Nagel, a professor of neurology and ophthalmology at the University of Colorado, said. School of Medicine, which was not involved in the study. In other words, brain changes seen in mild infections may not be driven by the same mechanisms as those seen in tissue of people who died from COVID-19, she told Live Science via email.
To evaluate the 81 patients with mild infections, the team performed magnetic resonance imaging (MRI) of their brains and compared them with scans of 145 volunteers without COVID-19. They found that certain regions of the cerebral cortex – the wrinkled surface of the brain responsible for complex processes such as memory and perception – had significant differences in thickness between the two groups.
“It was amazing,” said study author Dr. Clarissa Lin Yasuda, an assistant professor in the Department of Neurosurgery and Neurology at the University of Campinas, said.
The MRI scans were taken about two months after the diagnosis of each COVID-19 patient, but ‘in two months I would not expect such changes’, assuming that the patients’ brains once looked more like the uninfected participants ‘, Yasuda said. Usually, only prolonged, persistent insults cause changes in the cortex thickness, she added. Chronic stress, drug abuse and infections such as HIV Nagel said that this is accompanied by changes in cortical thickness, for example.
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In the COVID-19 patients, regions of the cortex located just above the nose showed significant thinning, suggesting that the nose and related sensory nerves may be an important pathway for the virus in the brain, Yasuda said. . That said, the virus probably does not invade everyone’s brains; but even in those who avoid direct brain infection, immune responses such as infection can sometimes damage the brain and dilute the cortex, Yasuda said. This particular study cannot show whether direct infection or inflammation drove the differences; it only shows a correlation between COVID-19 and cortex thickness, Nagel noted.
To better understand how frequently and how extensively SARS-CoV-2 penetrates the brain, the team collected brain samples from 26 patients who died from COVID-19, and found in five of the 26 brain damage.
The damage included patches of dead brain tissue and markers of inflammation. The team also detected SARS-CoV-2 genetic material and the viral “ear protein“” which protrudes from the surface of the virus, in all five of the patients’ brains. These findings indicate that their brain cells are directly infected by the virus.
The majority of the infected cells were astrocytes, followed by neurons. Martins-de-Souza said that once SARS-CoV-2 reaches the brain, it is more susceptible to infections than neurons.
To the laboratory
With this new data in hand, the team went to the laboratory to conduct experiments with stem cell-derived human astrocytes, to test how the coronavirus breaks into these cells and how it responds to infection.
Astrocytes have no ACE2 receptors, the main door that the coronavirus uses to enter cells, the authors found; it confirmed several previous studies showing a lack of ACE2 in the star-shaped cells. Instead, astrocytes have a receptor called NRP1, another entrance portal that the vein protein can penetrate to cause infection, the team found. “It is well known among coronavirus researchers that ACE2 is not just needed to introduce viruses into cells,” and that NRP1 sometimes serves as a different gateway, Nagel said.
When the researchers blocked NRP1 in laboratory dish experiments, SARS-CoV-2 did not infect astrocytes. Once the virus slides into an astrocyte, the star-shaped cell begins to function differently, the authors found. In particular, the cell begins to burn higher glucose, but oddly enough, the normal by-products of this process decrease. These by-products include pyruvate and lactate, which use neurons as fuel and to build neurotransmitters – the chemical messengers of the brain.
“And it will, of course, affect all the other roles that the neurons play in the brain,” Martins-de-Souza said.
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Data from the deceased COVID-19 patients have a backup on what they saw in the laboratory; for example, the infected brain samples also had unusually low levels of pyruvate and lactate compared to SARS-CoV-2 negative samples.
Back in the lab, the authors also found that infected astrocytes secrete “an unknown factor” that kills neurons; they discovered this by placing neurons in a medium where astrocytes were previously incubated with SARS-CoV-2. The dying neurons could, at least in part, explain how the cerebral cortex became so thin in COVID-19 patients with mild infections, the authors noted.
“It could somehow connect to the beginning of the story – that we saw these changes in living people,” Martins-de-Souza said. But that’s just a hypothesis, he added.
“We do not yet know if mild COVID-19 patients have a viral infection in the brain. It is therefore speculative to link the changes in cortical thickness to the astrocyte-related neuronal death,” Nagel said. In addition, ‘results in a dish may be different than in the brain in vivo, “so the findings need to be checked human brains, she added.
Next steps
Martins-de-Souza and his team look forward to investigating how glucose metabolism goes wrong in infected astrocytes, and whether the virus somehow diverts the extra energy to stimulate its own replication, he said. They also investigate the unidentified factor that causes neuronal death.
The team will also follow up the live patients in the study and collect more MRI scans to see if the cerebral cortex stays thin over time, Yasuda said. They will also collect blood samples and data on psychological symptoms, such as brain fog, memory problems, anxiety or depression. They have already begun studying how the observed changes in cortical thickness may be related to how brain cells send signals or build new connections between each other, according to a statement.
“We are very curious to see if these clinical and neuropsychological changes are permanent,” Yasuda said. Additional studies of people with moderate to severe infections will help determine how these individuals differ from those with mild illnesses.
And in the long run, the team will monitor for new brain-related conditions that may occur in their patients, such as dementia or other neurodegenerative diseases, to determine if COVID-19 is somehow increasing their likelihood.
“I hope not to see it,” Yasuda said. “But everything was so surprising to us that we may see these undesirable problems in the future.”
Originally published on Live Science.