They discover the mechanism that causes the loss of smell by covid

  • The virus causes the release of proteins that modify the genetic activity of olfactory nerve cells

Researchers have discovered a mechanism that could explain why covid-19 patients lose their sense of smell. Published in cell magazinethe new study finds that the infection indirectly reduces the action of olfactory receptors (OR), proteins located on the surface of nerve cells in the nose that detect molecules associated with odors. Led by researchers at the Grossman School of Medicine at New York University and Columbia Universitythe report also sheds light on the effects of coronavirus on other types of brain cells and on other lingering neurological effects, such as “brain fog,” headaches, and depression.

Experiments have shown that the presence of the virus near nerve cells in the olfactory tissue triggers a surge of immune cells, microglia and T cells, which detect and counter infection. These cells release proteins called cytokines that modify the genetic activity of olfactory nerve cells, even though the virus cannot infect them. While the activity of immune cells would dissipate rapidly in other scenarios, in the brain, according to the authors, immune signaling persists in such a way that it reduces the activity of genes necessary for the construction of olfactory receptors.

The work, added to another study by tenOever’s group, also suggests how the pandemic virus, which infects less than 1% of cells in the human body, it can cause such serious damage to so many organs. According to the researchers, a unique symptom of the infection is loss of smell without the nasal congestion seen in other infections such as the common cold. In most cases, the loss of smell lasts only a few weeks, but in more than 12% of patients, olfactory dysfunction persists in the form of a continued reduction in the ability to smell (hyposmia) or changes in the way the person perceives the same odor (parosmia). To better understand virus-induced loss of smell, the researchers explored the molecular consequences of SARS-CoV-2 infection in golden hamsters and in olfactory tissue taken from 23 human autopsies. The hamsters they represent a good model, since they are mammals that depend more on the sense of smell than humans and are more susceptible to infection of the nasal passages.

three-dimensional relationships of DNA

The study results are based on the discovery, made over many years, that the process that turns genes on involves complex three-dimensional relationshipsin which sections of DNA become more or less accessible to the cell’s gene-reading machinery based on key signals, and in which some strands of DNA loop to form long-range interactions that allow stable reading of the genes.

Some genes operate in chromatin “compartments” – protein complexes that house genes – that are open and active, while others are compacted and closed, as part of the “nuclear architecture”. In the study, experiments confirmed that SARS-CoV-2 infection, and the immune reaction to it, decreases the ability of DNA strands on chromosomes to influence olfactory receptor building formation to be open and active, and to loop to activate gene expression. In both hamster and human olfactory neuronal tissue, the research team detected a persistent and widespread downregulation of olfactory receptor construction. Other work published by these authors suggests that olfactory neurons are connected to sensitive brain regions, and that ongoing immune cell reactions in the nasal cavity could influence emotions and the ability to think clearly (cognition).

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Experiments conducted in hamsters and recorded over time revealed that receptor downregulation of olfactory neurons persisted after short-term changes that might affect the sense of smell had naturally recovered. The authors say this suggests that COVID causes a longer-lasting disruption in chromosomal regulation of gene expression, representing a form of “nuclear memory” that could prevent restoration of OR transcription even after removal of the virus. SARS-CoV-2. “The finding that the sense of smell depends on ‘fragile’ genomic interactions between chromosomes has important implications,” says tenOever.

“If olfactory gene expression ceases every time the immune system responds in certain ways that disrupt interchromosomal contacts, then the lost sense of smell could act like the ‘canary in the coal mine,’ providing any early sign that the virus is damaging brain tissue before other symptoms occur, and suggesting new ways to treat it,” he adds. In a next step, the team is studying whether treating long-Covid hamsters with steroids can curb damaging immune reactions (inflammation) to protect architecture. nuclear.

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