研究人員說，發現了導致 Covid-19 使嗅覺和味覺喪失的遺傳風險因素

Recently Yahoo News on-line reported the following:

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

NBC News - Sarah Sloat

Mon, January 17, 2022, 8:03 AM

Scientists are piecing together why some people lose their sense of smell after contracting Covid-19.

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

Six months after contracting 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 precise cause of sensory loss related to Covid is not known, but scientists do think 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 smell.

“How we get from infection to smell loss remains unclear,” said Dr. Justin Turner, an associate professor of otolaryngology at Vanderbilt University who was not a part of the study.

“Early data suggests that supporting cells of the olfactory epithelium are the ones mostly being infected by the virus, and presumably this leads to the death of the neurons themselves,” he said. “But we don’t really, really know why and when that happens, and why it seems to preferentially happen in certain individuals.”

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

This genetic risk factor increases the likelihood a person infected with SARS-CoV-2 will experience a loss of smell or taste by 11 percent. While some estimates suggest 4 out of 5 Covid patients regain these senses, research suggests the persistent inability or reduced ability to smell and taste impacts relationships, physical health and psychological 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 U.S. or the United Kingdom.

Within a group of 69,841 individuals who self-reported receiving a positive Covid test, 68 percent reported a loss of smell or taste as a symptom. The loss of smell and taste were combined as a single survey question; this grouping and the use of self-reported data are 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 this effect, the study team found a region of the genome associated with this split that’s situated near two genes, UGT2A1 and UGT2A2. Both of these genes are expressed within tissue inside the nose involved in smell and play a role in metabolizing odorants.

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

How UGT2A1 and UGT2A2 are involved in this process is unclear, though he and his colleagues hypothesize the genes “may play a role in the physiology of infected cells” and the resulting impairment that leads to smell loss.

To use these findings, scientists 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 the 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 people of “East Asian or African American ancestry were significantly less likely to report loss of smell or taste.” The cause of this observation is not yet known, but Auton said it’s likely not explained by the genetic variants of this specific locus. The team also notes the study is biased toward people of European ancestry because of limited reference data.

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

First, “it helps answer the question of ‘why me’ when it comes to taste and smell loss with Covid-19,” she said. “Some people have it and some do not. Inborn genetics may partially explain why.”

The study may also help scientists find treatments. Earlier research suggests the loss of these senses is related to a “failure to protect the sensory cells of the nose and tongue from viral infection,” Reed said.

“This study suggests a different direction,” she said. “The pathways that break down the chemicals that cause taste and smell in the first place might be over or underactive, reducing or distorting the ability to taste and smell.”

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

Translation

科學家們正在重組出為什麼有些人在感染 Covid-19 後會失去嗅覺。

週一發表在 Nature Genetics 雜誌上的一項研究確定了與 Covid 感染後嗅覺喪失相關的遺傳風險因素，這一發現使專家更接近於了解令人困惑的模式，並可能為急需的治療指出方向。

美國多達 160 萬人在感染新冠病毒六個月後，仍然無法聞到氣味，或者他們的嗅覺能力發生了變化。與新冠病毒相關的感覺喪失的確切原因尚不清楚，但科學家們確實認為它源於鼻子一部分被稱為嗅上皮的受感染細胞的損傷。這些細胞保護嗅覺神經元，以幫助人類嗅覺。

沒有參與這項研究的Vanderbilt大學耳鼻喉科副教授Justin Turner博士說: “我們仍不清楚如何由感染至到嗅覺喪失” 。

他說: “早期數據表明，嗅覺上皮的支持細胞是最常被病毒感染的細胞，這可能會導致神經元本身死亡”; “但我們實在地、真的不知道為什麼以及何時發生這種情況，以及為什麼它似乎更喜歡發生在某些人身上。”

根據這項研究，兩個嗅覺基因附近的一個基因座與新冠病毒引起的嗅覺和味覺喪失有關。基因座是基因在染色體上的固定位置。

這種遺傳風險因素使感染 SARS-CoV-2 的人失去嗅覺或味覺的可能性增加了 11%。雖然一些估計表明，五分之四的 Covid 患者恢復了這些感官，但研究表明，持續無法或嗅覺和味覺能力下降會影響人際關係、身體健康和心理健康。

基因組學和生物技術公司 23andMe 的研究人員將這項研究作為更大的 Covid 項目的一部分進行。所有參與者都居住在美國或英國。

在一組 69,841 名自我報告接受 Covid 檢測呈陽性的人中，68% 的人報告喪失嗅覺或味覺的症狀。嗅覺和味覺的喪失被合併為一個調查問題；這種分組方式和使用自我報告方式的數據是該研究的局限性。

在比較了那些失去嗅覺的人, 和那些報告說他們沒有受到這種影響的人之間的遺傳差異後，研究小組發現了與這種分岐相關的基因組區域，該區域位於兩個基因 UGT2A1 和 UGT2A2 附近。這兩個基因都在鼻子內部與氣味有關的組織中表現出來，並在氣味代謝中發揮作用。

23andMe 的人類遺傳學副總裁 Adam Auton 兼該研究的主要作者說:“這是一個非常漂亮的科學例子，從大量已完成 23andMe 測試的活躍研究參與者開始，我們能夠非常迅速地獲得對這種疾病的一些生物學見解，其他途徑這是很難做到”。

UGT2A1 和 UGT2A2 是如何參與這一過程尚不清楚，儘管他和他的同事假設這些基因“可能在受感染細胞的生理學中起作用”, 並導致嗅覺喪失的損害。

Justin Turner說，為了利用這些發現，科學家們需要更多地了解這些基因的表現形式, 以及它們在嗅覺信號傳導中的功能。

在報告嗅覺和味覺喪失的參與者中也出現了某些趨勢：例如，女性經歷這種情況的可能性比男性高 11%。與此同時，26 至 35 歲的成年人佔該群體的 73%。

研究小組還發現， “具有東亞或非裔美國人血統的人報告嗅覺或味覺喪失的可能性顯著降低” 。這種觀察的原因尚不清楚，但 Adam Auton 說這可能無法用這個特定基因座的遺傳變異來解釋。該團隊還指出，由於參考數據的限制，該研究是向歐洲血統的人倾斜。

Monell Chemical Senses Center 副主任 Danielle Reed 說，這些發現可以通過兩種方式幫助患者。她研究了因 Covid 而導致的嗅覺和味覺喪失的人與人之間的喪失差異，這並不是這新論文的一部分。

首先，她說 :“在 Covid-19 導致味覺和嗅覺喪失方面，它有助於回答 ‘為什麼是我’ 這個問題”; “有些人有，有些人沒有。先天遺傳學可能部分解釋了原因。”

該研究還可以幫助科學家找到治療方法。Danielle Reed說: “早期的研究表明，這些感官的喪失與“未能保護鼻子和舌頭的感覺細胞免受病毒感染有關”。

她說: “這項研究提出了一個不同的方向”; “分解負責引起味覺和嗅覺的化學物質的途徑本身可能是過度或不活躍，從而降低或扭曲了味覺和嗅覺的能力” 。

在大多數冠狀病毒大流行中，嗅覺和味覺的喪失被稱為標誌性症狀。 早期研究表明，因 omicron 變體而使氣味和味覺喪失是較少見，但並非完全不可能：在對挪威 81 個 omicron 病例的研究中，12% 的人報告嗅覺減少，23 人報告味覺減少。

       So, early data suggests that supporting cells of the olfactory epithelium are the ones mostly being infected by the virus, and presumably this leads to the death of the neurons themselves. I hope such finding could help us find out a way to restore the smell and taste sensors.

Note:

23andMe, Inc. is a publicly held personal genomics and biotechnology company based in Sunnyvale, California. It is best known for providing a direct-to-consumer genetic testing service in which customers provide a saliva sample that is laboratory analyzed, using single nucleotide polymorphism genotyping, to generate reports relating to the customer's ancestry and genetic predispositions to health-related topics. The company's name is derived from the 23 pairs of chromosomes in a wildtype human cell. (Source: https://en.wikipedia.org/wiki/23andMe)