COVID fuses brain cells, which could explain brain fog

The SARS-CoV-2 coronavirus triggers an infection in the respiratory system, but it also affects other areas of the body and there is increasing scientific evidence of the presence of viral RNA and proteins in the brain and the appearance of numerous neuropsychiatric syndromes in the early stages of the disease, which last months after infection and are part of the set of symptoms known as persistent or prolonged COVID.

A new study conducted by researchers at the University of Queensland (Australia) has now discovered that viruses such as SARS-CoV-2 can cause people to brain cells to fusegiving rise to defects that lead to chronic neurological symptomssuch as brain fog, headache, and difficulty concentrating. “We discovered that COVID-19 causes neurons to undergo a process of cell fusion, which had not been seen before,” explained Professor Massimo Hilliard that he has explored with Dr. Ramón Martínez-Marmol – both from the Queensland Brain Institute – how viruses alter nervous system function.

These scientists recall that the coronavirus has been detected in the brains of people with persistent COVID months after the initial infection, as well as in autopsies of people who died with COVID-19. “After the neuronal infection with SARS-CoV-2, the Spike S protein becomes present in neurons, and once the neurons fuse, they don’t die.” “Either they start firing synchronously or they stop working altogether,” adds Hilliard.

“When a virus enters the brain, there are two results: cell death or inflammation, but we have shown a third possible result, which is neuronal fusion”

The researcher has compared the role that neurons play with that of the cables that connect the light switches in a kitchen and a bathroom: “Once the fusion is carried out, each switch turns on the kitchen and bathroom lights.” bathroom at the same time, or neither of them,” he said, noting that this is bad news “for the two independent circuits.”

Their findings have been published in Science Advances and provide a potential explanation for the neurological effects that persist after viral infection. “In the current understanding of what happens when a virus enters the brain, there are two outcomes: cell death or inflammation,” says Dr. Martinez-Marmol, “but we have shown a third possible outcome, which is neuronal fusion. ”.

Interference in communication between neurons

To carry out the study, the researchers genetically engineered two populations of mouse neurons: one expressed a red fluorescent molecule and the other a green fluorescent molecule. If the two were fused together in a lab dish they would look bright yellow under a microscope, and that’s what the researchers saw when they added SARS-CoV-2 to a dish containing the two cell types, they explain in the published paper. in the scientific journal. This same merger occurred in the human brain organoids –mini brains– that are created from stem cells.

The key seems to be angiotensin converting enzyme 2 (ACE2), the protein present on the surface of mammalian cells through which SARS-CoV-2 infects the organism. The virus uses the spike protein to bind to ACE2, allowing it to fuse with a cell and release its genetic material inside. Apparently, the spike protein in infected cells can also cause other ACE2s in one cell to trigger fusion with a neighboring cell. When the researchers engineered the neurons to express the spike protein, only cells that also expressed ACE2 were able to fuse with each other.

However, they found differences between the fusion of lung and neuronal cells, since the fusion between the neurons occurred in the dendrites and axons, which are key to communication between them. The mergers seemed to interrupt this communication. The neurons normally fire independently, sending signals throughout the brain, but 90% of the fused neurons fired at the same time, while the remaining 10% remained silent.

This enormous amount of synchronous activity “is almost like a seizure,” says Hilliard. The brain fog could happen when this delicate communication is interrupted, he says. Previously, Hillard’s team had shown that inducing neurons to fuse in the worm’s nervous system Caenorhabditis elegans decreases its ability to detect odors.

Dr. Martínez-Mármol has explained that there are many viruses that cause cell fusion in other tissues, but they also infect the nervous system and could be causing the same problem there. “These viruses include HIV, rabies, Japanese encephalitis, measles, herpes simplex virus, and Zika virus,” he said. “Our research reveals a new mechanism for the neurological events that occur during a viral infection. This is potentially an important cause of neurological disease and clinical symptoms that has yet to be explored,” she concludes.


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