How COVID-19 causes odor loss

Temporary odor loss, or anorexia, is a major neurological symptom and one of the earliest and most commonly reported indicators of COVID-19. Studies suggest that disease prediction is better than other well-known symptoms such as fever and cough, but the underlying mechanism by which COVID-19 patients lose their odor is unknown.

Currently, an international research team led by a neuroscientist at Harvard Medical University has identified the type of olfactory cell that is most vulnerable to infection by SARS-CoV-2, the virus that causes COVID-19.

Surprisingly, the sensory neurons that detect olfaction and transmit it to the brain are not among fragile cell types.

Report in Scientific progress On July 24, the research team found that olfactory sensory neurons do not express the gene encoding the ACE2 receptor protein. Human cell.. Instead, ACE2 is expressed on olfactory neurons and cells that provide metabolic and structural support to specific populations of stem and vascular cells.

Findings suggest that non-neuronal cell type infections may be responsible for anorexia in COVID-19 patients and help inform efforts to better understand disease progression doing.

“Our findings show that the new coronavirus alters the patient’s sense of smell by affecting the function of supporting cells rather than directly infecting neurons.”

This means that, in most cases, SARS-CoV-2 infection is unlikely to cause permanent damage to the olfactory neural circuit and cause persistent anosmia.

“Once the infection goes away, I think it’s good news, because there’s no need to replace olfactory neurons or rebuild them from scratch,” he said. “But we need more data and a better understanding of the underlying mechanism to confirm this conclusion.”

The vast majority of COVID-19 patients experience some level of numbness, mostly transient, according to new data. An analysis of electronic health records shows that COVID-19 patients are 27 times more likely to lose odor compared to those without COVID-19, but have a fever, cough, or dyspnea of ​​about 2.2 It is shown to be only 2.6 times.

Some studies suggest that COVID-19 anosmia differs from anosmia caused by other viral infections, including other coronaviruses.

For example, COVID-19 patients usually recover their olfaction over a period of weeks. It takes much longer than a month to recover from anolence caused by a subset of viral infections known to directly damage olfactory neurons. In addition, many viruses are temporary Loss of smell By causing upper respiratory problems such as stuffy nose. However, some COVID-19 patients experience anorexia without nasal congestion.

Vulnerability identification

In the current study, Datta and colleagues sought to better understand how olfactory changes in COVID-19 patients are altered by identifying the cell types most vulnerable to SARS-CoV-2 infection. It was

They started by analyzing an existing single-cell sequence data set that cataloged the sum of genes expressed by hundreds of thousands of individual cells in the upper nasal cavity of human, mouse, and nonhuman primates. It was.

The team focused on the ACE2 gene, which is predominant in cells of the human respiratory tract and encodes a major receptor protein that SARS-CoV-2 targets for the purpose of entering human cells. They also examined another gene, TMPRSS2, which encodes an enzyme that is thought to be important for SARS-CoV-2 entry into cells.

Analysis reveals that both ACE2 and TMPRSS2 are expressed by cells of the olfactory epithelium, a specialized tissue on the roof of the nasal cavity responsible for odor detection that houses olfactory neurons and various supporting cells. It was

However, neither gene was expressed in olfactory neurons. In contrast, these neurons expressed genes associated with the ability of other coronaviruses to enter the cell.

Researchers have shown that two specific cell types in the olfactory epithelium express ACE2 at levels similar to those observed in cells of the lower respiratory tract, the most common target of SARS-CoV-2, and It has been found to suggest a vulnerability to.

These included supporting cells, which are thought to wrap sensory neurons and provide structural and metabolic support, and basal cells that function as stem cells to regenerate the olfactory epithelium after injury. The presence of proteins encoded by both genes in these cells was confirmed by immunostaining.

In additional experiments, the researchers found that olfactory epithelial stem cells express higher levels of ACE2 protein after artificially induced injury compared to resting stem cells. This may suggest additional SARS-CoV-2 vulnerabilities, but whether or how this is important for the clinical course of anorexia in COVID-19 patients. Remains unknown.

Datta et al. also analyzed gene expression in approximately 50,000 individual cells of the mouse olfactory bulb. Olfactory neurons In charge of the initial odor treatment.

Olfactory bulb neurons did not express ACE2. Genes and related proteins were only present in vascular cells, especially pericytes involved in blood pressure regulation, maintenance of the blood-brain barrier and inflammatory responses. There was no olfactory bulb cell type expressing the TMPRSS2 gene.

Olfactory clues

Taken together, these data suggest that COVID-19-related analgesia may result from a temporary loss of supporting cell function. Olfactory epitheliumIndirectly causes olfactory changes Sensory neurons, The authors said.

“But I don’t fully understand what these changes are,” said Datta. “Collagen cells are largely ignored, and it seems that attention needs to be paid to them just as they are increasingly aware of the important role glial cells play in the brain.”

The findings also provide interesting clues to COVID-19-related neurological problems. Observations are consistent with the hypothesis that SARS-CoV-2 is not directly transmitted Neuron Instead it may interfere with brain function by affecting blood vessels cell In the nervous system, the author said. They added that further research is needed to verify this.

The findings of this study will help accelerate efforts to better understand odor loss in COVID-19 patients. This may lead to the treatment of anosmia and improved olfactory-based diagnosis.

“Although olfaction seems like a strange phenomenon, it can be devastating to the few people who persist,” Datta said. “It can have serious psychological consequences and can be a major public health problem if our population continues to grow and smells are lost forever.”

The team also hopes that this data will help pave the way for questions about disease progression, such as whether the nose functions as a reservoir for SARS-CoV-2. Such efforts would require experimentation with live coronaviruses and research in a facility that would allow analysis of human autopsy data, the author said, which is still difficult to obtain. But the collaborative spirit of scientific research during the pandemic era calls for optimism.

“In my lab, I started this work because I had some datasets that could be analyzed when a pandemic occurred, and I published the first preprint,” Datta said. “What happened after that was amazing. Researchers around the world offered to share and merge their data with some kind of improvised global consortium. It was a result of.”