Revealing the mechanism of novel coronavirus pneumonia leading to olfactory loss From Cell

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After infection with the new crown, a major symptom of patients is the loss of smell. However, the mechanism behind this symptom has not been clarified. In a new study, researchers from research institutions such as Columbia University and Icahn School of medicine in Mount Sinai found a mechanism that may explain why patients with covid-19 lose their sense of smell. Specifically, they found that infection with the pandemic virus sars-cov-2 indirectly lowered the role of the olfactory receptor (or), a protein on the surface of nerve cells (neurons) in the nose, which can detect odor related molecules. The relevant research results were published online in the journal Cell on February 1, 2022.

The new study may also clarify the effects of covid-19 on other types of brain cells, as well as other lingering neurological effects of covid-19, such as “brain fog”, headache and depression.

Experiments have shown that the presence of the virus near neurons in olfactory tissue brings an influx of immune cells – microglia and T cells – that can sense and fight infection. These immune cells release proteins called cytokines that alter the genetic activity of olfactory neurons, even if the virus cannot infect them, the authors said. According to their theory, the activity of immune cells dissipates rapidly in other cases, while in the brain, the persistence of immune signals reduces the activity of genes expressing olfactory receptors.

Picture from cell, 2022, DOI: 10.1016/j.cell 2022.01.024。

Dr. Benjamin ten oever, co-author of the paper and professor of Microbiology at New York University’s langney medical center, “Our findings provide the first mechanistic explanation for the loss of smell of covid-19, and this may be the biological basis of long-term sequelae of new crown (covid-19). In addition to another study by tenoever team (immunity, 2021, DOI: 10.1016 / j.immuni. 2021.01.017) In addition, this study also shows how the pandemic virus sars-cov-2, which infects less than 1% of human cells, can cause such serious damage in so many organs. “

structural changes

A unique symptom of covid-19 infection is loss of smell and no nasal congestion like other infections such as the cold virus, the authors said. In most cases, olfactory loss lasts only a few weeks, but for more than 12% of covid-19 patients, olfactory dysfunction persists, manifested as a continuous decline in olfactory ability (olfactory decline) or a change in a person’s perception of the same smell (olfactory reversal).

To gain insight into covid-19-induced olfactory loss, the authors explored the molecular consequences of sars-cov-2 infection in golden hamsters and olfactory tissues extracted from 23 human cadavers. Hamsters represent a good model. They are mammals that rely more on smell than humans and are more vulnerable to nasal infections.

These research results are based on the discovery over the years, that is, the process of opening genes involves complex three-dimensional relationships, in which DNA fragments are more or less accessed by the gene reading complex of the cell according to the key signals. Some DNA chains form a ring structure and produce the interaction of growth distance, so that the genes can be read stably. Some genes operate in open and active chromatin “compartments” – protein complexes containing genes, while others are compact and closed and are part of the “nuclear architecture”.

In this new study, the experiment confirmed that sars-cov-2 infection and immune response to it reduced the opening and activity of chromosomal DNA strand affecting the formation of olfactory receptor, as well as the ability to form ring structure and activate gene expression. In hamster and human olfactory nerve tissues, these authors detected sustained and extensive down-regulation of olfactory receptor expression. Another study they released showed that olfactory neurons are connected to sensitive brain regions, and the continuous immune cell response in the nasal cavity may affect emotion and the ability to think clearly (cognition), which is consistent with the long-term sequelae of Xinguan.

Experiments recorded in hamsters showed that the down-regulation of olfactory neuronal receptors still existed after the natural recovery of short-term changes that may affect olfaction. These authors say that this indicates that covid-19 has caused more lasting damage to the chromosomal regulation of gene expression, representing a form of “nuclear memory”, which may prevent the recovery of olfactory receptor transcription even after sars-cov-2 is cleared.

Ten oever said, “It is important to realize that smell depends on ‘fragile’ genomic interactions between chromosomes. If olfactory gene expression stops every time the immune system destroys chromosome to chromosome contact in some way, the lost smell may act as a ‘canary in the coal mine’, providing any evidence that sars-cov-2 virus is destroying brain tissue before other symptoms appear Early signal and propose new methods of treatment. “

Next, the authors are studying whether treating hamsters with steroids for the long-term sequelae of the new crown can inhibit the destructive immune response (inflammation) to protect the nuclear structure.

reference material:

Marianna Zazhytska et al. Non-cell autonomous disruption of nuclear architecture as a potential cause of COVID-19 induced anosmia. Cell, 2022, doi:10.1016/j.cell.2022.01.024.

Mechanism Revealed Behind Loss of Smell with COVID-19

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