Science sub-journal explores in depth how the new coronavirus causes a loss of sense of smell in patients.

!--:page title"--August 2, 2020 /prNewswire/ -- --- temporary loss of sense of smell is the main neurological symptom of COVID-19 and one of the earliest and most frequently reported indicators of the disease.
existing research suggests that it is more predictable than other well-known symptoms such as fever and cough, the basic mechanism of olfactory loss in patients with COVID-19 has been unclear.
now, in a new study, an international team of neuroscientists at Harvard Medical School in the United States has identified the types of olfactory cells most susceptible to SARS-CoV-2, the new coronavirus that causes COVID-19.
surprising, the sensory neurons that detect the odor and transmit it to the brain are not the type of cell that is susceptible to infection.
they found that olfactory sensory neurons did not express the ACE2 receptor protein used by SARS-CoV-2 to enter human cells.
, ACE2 is expressed in cells that provide metabolic and structural support for olfactory neurons, as well as in certain stem cell and vascular cell populations.
recently published the results of the study in the journal Science Advances, entitled "Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system spartners smechanisms underlying COVID-19-associated anosmia".
diagrams of the upper skin, the upper skin and the olfactory ball in the nasal tract.
images from Science Advances, 2020, doi: 10.1126/sciadv.abc5801.
these findings suggest that infections of non-neuronal cell types may be the cause of loss of smell in patients with COVID-19, which helps to better understand the progression of the disease. "Our results suggest that the new coronavirus changes the patient's sense of smell not by directly infecting neurons, but by affecting the function of supporting cells," said Sandeep Robert Datta, a
paper's author and associate professor of neurobiology at Harvard Medical School's Blavatnik Institute.
" Datta added that this means that in most cases, SARS-CoV-2 infection is less likely to permanently damage the olfactory neural circuit and lead to persistent loss of smell, which is associated with a variety of mental and social health problems, particularly depression and anxiety. "I think that's good news because once the infection is cleared, the olfactory neurons don't seem to need to be replaced or rebuilt from scratch,"
said.
we need more data and a better understanding of the inner mechanisms to confirm this conclusion. "According to emerging data, most PATIENTS with COVID-19 experience some degree of loss of smell, most commonly temporary olfactory loss,"
.
analysis of electronic health records showed that patients with COVID-19 were 27 times more likely to experience loss of smell than those without COVID-19, but only about 2.2 to 2.6 times more likely to develop fever, cough or breathing difficulties.
some studies suggest that the loss of sense of smell in patients with COVID-19 is different from the loss of sense of smell caused by other viral infections, including other coronaviruses.
, for example, patients with COVID-19 usually regain their sense of smell within a few weeks--- much faster than the months of loss of smell due to a group of virus infections known to directly damage the olfactory neurons.
in addition, many viruses cause temporary loss of sense of smell by causing upper respiratory problems, such as nasal congestion.
However, some PATIENTs with COVID-19 also experience loss of sense of smell without any nasal congestion.
identify susceptibility In this new study, Datta and his colleagues set out to better understand how the sense of smell changes in PATIENTs with COVID-19 by identifying the types of cells most susceptible to SARS-CoV-2 infection.
they first analyzed existing single-cell sequencing data sets that aggregate the genes expressed by thousands of cells in the nasal cavity of humans, mice and non-human primates.
the researchers focused on ace2, a gene widely found in human respiratory cells that encodes a major receptor protein used to enter human cells.
they also studied another gene, TMPRSS2, which encodes enzymes that are considered an important factor in the entry of SARS-CoV-2 into cells.
analysis showed that BOTH ACE2 and TMPRSS2 are expressions of olfactory cells--- the olfactory epithelial cells are the special tissue responsible for odor detection at the top of the nasal cavity, with olfactory neurons and various support cells.
however, the olfactory neurons do not express both genes.
, instead, these neurons do express genes associated with the ability of other coronaviruses to enter cells.
the researchers found that the levels of ACE2 expression in two specific cell types in the olfactory epithelial were similar to those observed in lower respiratory cells.
Given that lower respiratory cells are the most common targets for SARS-CoV-2, this suggests that these two specific cells are also susceptible to infection.
these two specific cells include stalfocells that wrap olfactory sensory neurons and are thought to provide structural and metabolic support;
confirmed the presence of proteins encoded by these two genes in both cells through immunostaining.
in further experiments, the researchers found that olfactory epithelial stem cells had higher levels of expression of the ACE2 protein after artificially induced damage during the still period.
Datta and his colleagues also analyzed the gene expression of nearly 50,000 cells in the mouse olfactory ball, the structure of the pre-brain that receives signals from olfactory neurons, responsible for the initial odor processing.
neurons in the olfactory ball do not express ACE2.
no cell type expression of the TMPRS2 gene in the olfactory sphere.
in the olfactory ball, the gene and its associated proteins are present only in vascular cells, especially the peripheral cells involved in blood pressure regulation, blood-brain barrier maintenance, and inflammatory responses.
olfactory loss clues, the researchers say the data together suggest that THE OLFACTORy loss associated with COVID-19 may be due to a temporary loss of supporting cellular function in the olfactory epithelial, which indirectly leads to changes in olfactory neurons.
!--/ewebeditor:!--webeditor:page:page title" - "However, we don't fully understand what these changes are."
pillar cells are largely neglected, and it seems that we need to pay attention to them, similar to our growing emphasis on the key role that glial cells play in the brain.
"These findings also provide interesting clues to the neurological problems associated with COVID-19."
the researchers, the findings are consistent with the hypothesis that SARS-CoV-2 does not directly infect neurons but may interfere with brain function by affecting blood vessel cells in the nervous system.
added that further research was needed to verify it.
these findings now help speed up research to better understand the loss of sense of smell in patients with COVID-19, which could lead to the development of ways to treat loss of olfactory loss and to the development of improved olfactory-based disease diagnosis methods. "Loss of smell may seem like a strange phenomenon, but it can be devastating for a small percentage of people whose loss of sense of smell persists," said
Datta.
it can have serious psychological consequences, and if we have more and more people permanently losing their sense of smell, it could be a major public health problem.
" the researchers also hope the data will help solve problems of disease progression, such as whether the nose plays a role as a library of SARS-CoV-2 viruses.
say this will require research and analysis of human autopsy data at facilities that allow experiments with live coronaviruses, which are still difficult to obtain.
However, the spirit of cooperation in scientific research during the pandemic is optimistic. "We started this study because I had several data sets in my lab ready for analysis, and when the COVID-19 pandemic hit, we published the first preprinted study," said
Datta. What happened after
was amazing, and researchers around the world proposed sharing and merging their data with us, an impromptu global alliance.
this is a real achievement of cooperation.
" (bioon.com) References: 1. David H. Brann et al. Non-neuronal expression of SARS-CoV-2 entry genes in the olfaory system suggests mes yn dallyyn COVID-19-associated anosmia. Science Advances, 2020, doi: 10.1126/sciadv.abc5801.2.How COVID-19 causes smell loss.