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Genetic risk factor found for Covid-19 odor and taste loss, researchers say

Researchers are figuring out why some people lose their sense of smell after getting Covid-19.

A study published Monday in the journal Nature Genetics identified a genetic risk factor associated with the loss of odor after a Covid infection, a discovery that brings experts closer to understanding the confusing pattern and may point the way to much-needed treatments.

Six months after receiving Covid, as many as 1.6 million people in the United States are still unable to smell or have experienced a change in their ability to smell. The exact cause of sensory loss related to Covid is not known, but researchers believe it stems from damage to infected cells in a part of the nose called the olfactory epithelium. These cells protect olfactory neurons, which help humans to smell.

"How we get from infection to odor loss is still unclear," said Dr. Justin Turner, an associate professor of otolaryngology at Vanderbilt University, who was not part of the study.

"Early data suggest that support cells in the olfactory epithelium are the ones that are mostly infected by the virus, and presumably this leads to the death of the neurons," he said. "But we do not really know why and when it happens and why it seems preferable to happen in certain individuals."

According to the study, a genetic locus near two olfactory genes is associated with Covid-induced loss of smell and taste. A locus is the fixed position of a gene on a chromosome.

This genetic risk factor increases the likelihood that a person infected with SARS-CoV-2 will experience loss of odor or taste by 11 percent. While some estimates suggest that 4 out of 5 Covid patients regain these senses, research suggests that the persistent inability or impaired ability to smell and taste affects relationships, physical health, and mental well-being.

Researchers at the genomics and biotechnology company 23andMe conducted the study as part of a larger Covid project. All participants live in the United States or the United Kingdom.

Within a group of 69,841 people who themselves reported having received a positive Covid test, 68 percent reported loss of odor or taste as a symptom. The loss of smell and taste was combined as a single research question; this grouping and the use of self-reported data are the limitations of the study.

After comparing the genetic differences between those who lost their sense of smell and those who reported that they did not suffer from this effect, the research team found a region of the genome associated with this cleavage located near two genes, UGT2A1 and UGT2A2. Both of these genes are expressed in tissues inside the nose involved in odor and play a role in the metabolism of odorants.

"It was this really beautiful example of science where, starting with a large group of activated research participants who performed this 23andMe test, we were very quickly able to gain some biological insights into this disease, which would otherwise be very , very difficult to perform. ", said Adam Auton, vice president of human genetics at 23andMe and lead author of the study.

How UGT2A1 and UGT2A2 are involved in this process is unclear, although he and his colleagues assume that genes "may play a role in the physiology of infected cells" and the consequent attenuation leading to odor loss.

To use these results, researchers need to learn more about how these genes are expressed and what their functions are in olfactory signaling, Turner said.

Certain trends also emerged among the participants who reported loss of smell and taste: Women, for example, were 11 percent more likely than men to experience this. Meanwhile, adults between the ages of 26 and 35 made up 73 percent of this group.

The study team also found that people of "East Asian or African American descent were significantly less likely to report loss of odor or taste." The reason for this observation is not yet known, but Auton said it is probably not explained by the genetic variants of this specific locus. The team also notes that the study is biased towards people of European descent due to limited reference data.

These findings could help patients in two ways, said Danielle Reed, associate director of the Monell Chemical Senses Center. She is studying person-to-person differences in loss of smell and taste due to Covid and was not part of the new paper.

First, "it helps answer the 'why me' question when it comes to taste and smell loss with Covid-19," she said. "Some people have it, and some do not. Congenital genetics may partly explain why."

The study may also help researchers find treatments. Previous research suggests that the loss of these senses is related to a "lack of protection of the sensory cells in the nose and tongue against viral infection," Reed said.

"This study suggests a different direction," she said. "The pathways that degrade the chemicals that cause taste and smell in the first place can be overactive or underactive, reducing or distorting the ability to taste and smell."

For most of the coronavirus pandemic, the loss of smell and taste has been known as signature symptoms. Early research suggests that loss of odor and taste is less common with the omicron variant, but not entirely unlikely: In a study of 81 omicron cases in Norway, 12 percent reported reduced odor and 23 reported reduced taste.

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