Olfactory disorder: the neglected sequelae of COVID-19

Olfactory disorder: the neglected sequelae of COVID-19.   In recent days, a special patient group is quietly growing. The patients who joined this organization have various but highly uniform symptoms:

The cherished perfume was sprayed on like rotten eggs, the tap water was flowing out of the faucet, and the smell of excrement was emitted from the first dinner after a serious illness.

Some people even claim that when they go to the toilet, they spray out “objects” with the aroma of roast beef tongue…

Smell failure, or even inverted sense of smell, is a disease that many patients in the patient group (AbScent) suffer every day.

In addition, these people have another thing in common-they were or are patients with the new coronavirus infection.

More than 40 million people may lose their sense of smell

It is a very common situation in life to find that there is no taste in eating for a few days after catching a cold. Many viruses, such as rhinovirus, parainfluenza virus, Epstein-Barr virus and some coronaviruses, etc., these viruses may indeed cause patients to experience smell and/or taste disorders for a period of time when infected.

The COVID-19 virus is no exception. Most studies have shown that smell problems are more common in patients with COVID-19.

In the early stage of the 2020 epidemic (from the end of January to the beginning of February), Wuhan Union Medical College Hospital found that patients with COVID-19 had olfactory disorders. The study was published in April. Since then, articles on the global study of the new coronavirus and olfactory and taste disorders have also begun to be published.

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In May last year, a preprinted platform MedRxiv published a global multi-center study that counted 4,039 new coronavirus patients and confirmed that the change in smell is a new atypical symptom of new coronavirus pneumonia. The counted COVID-19 patients all experienced hypoosmia or loss of smell to varying degrees, and even about 10% of patients reported that they had an inversion of smell. The study was published in Chem Senses in October.

A review also found that 41% of the approximately 8,000 patients with COVID-19 reported anosmia. In another study, a scientific research team conducted an olfactory evaluation of 100 patients with COVID-19, and found that 96% of the testers had different degrees of olfactory disorders, and 18% of them had completely lost their sense of smell.

In August, a meta-analysis hosted by the Mayo Clinic showed that after a meta-analysis of 24 related studies and nearly 9,000 patients with new coronavirus pneumonia, it was found that the prevalence of olfactory dysfunction was about 41.0%. Another study showed that patients with olfactory perversion accounted for about 10% of olfactory disorders.

According to the number of confirmed cases of new coronavirus pneumonia that has exceeded 100 million in the world, about 41 million patients are currently losing their sense of smell, and 4 million people may be falling into the trap of “your defecation, my honey”.

In AbScent, a group of patients with olfactory disorders, their self-estimated prevalence rate is 65%, which seems to be much higher than the prevalence rate given by the Mayo Clinic. However, an Iranian scientist engaged in related research once said on Twitter that the prevalence proposed by Absent may be more real, “In the new coronavirus pneumonia pandemic, there are only a lot more potential olfactory patients.”

He said that according to the current global anti-epidemic situation, a large number of COVID-19 patients and doctors have no chance to care about “olfactory disorders”-a symptom that does not cause immediate death. Even if the patient recovers and is discharged from the hospital, olfactory failure can still exist as a long-term sequelae.

With the increase in the number of confirmed patients, reports of olfactory failure in patients with COVID-19 after recovery are not uncommon.

For example, the British dignitaries, Prince Charles, shortly after his diagnosis on March 26 last year, informed the outside world that he had lost his sense of smell. Although Prince Charles recovered quickly, he still stated that his sense of smell and taste had not recovered until he visited the hospital in June.

Jennifer Spicer, an infectious disease doctor in the United States, also claimed that after recovering from the COVID-19 pneumonia, he found that coffee, wine, and other foods tasted like gasoline.

Even a Harvard researcher found in a community experiment that patients currently suffering from olfactory failure due to the COVID-19 may be just the tip of the iceberg.

The experiment was inspired by an odd piece of news: Amazon’s scented candle shop received a large number of negative reviews in 2020 because of the weakening of the fragrance, but the strange thing is that the raw materials of this scented candle have not changed in any way.

A study calculated relevant data and found that throughout 2020, the score of this scented candle shop did gradually decline as the epidemic progressed. Among them, there are more and more scores that complain about no fragrance, less fragrance, or smelly fragrance.

The top is scented candles, and the bottom is unscented candles. The score drop is relatively obvious.
(Twitter screenshot)

Interestingly, a British medical doctor also conducted relevant analysis inspired by the research. Coincidentally, he found a similar phenomenon in the perfume sector of the British Amazon.

They expressed horror on Twitter. Does this strange phenomenon mean that a large number of people do not even know that they have been infected with the new coronavirus after impaired smell? The result is unknown.

Unknown mechanism, limited treatment

At present, the mechanism of how the new coronavirus causes olfactory disorders in patients has not yet been fully clarified. At present, the medical profession is also in disagreement.

When medical scientists defined olfactory dysfunction as a symptom of new coronavirus pneumonia last year, the hypothesis put forward in the discussion was that the new coronavirus may infect odor-sensing neurons in the nose. These neurons transmit signals to the olfactory bulb of the brain. The virus will take this to Huanglong.

The theoretical basis of this hypothesis comes from the underlying neural characteristics of the new coronavirus. Previously, after intranasal administration of SARS-CoV (highly similar to the new coronavirus) in transgenic mice, some scholars found that the virus can penetrate into the brain through the olfactory bulb, causing rapid spread across neurons.

Recently, an anatomical study published in the Nature sub-journal showed that the new coronavirus may enter the brain from the nose and spread along nerve cells. In this study, the scientists also obtained a complete electron microscope image of the new coronavirus particles inside the nasopharynx for the first time.

There are a large number of complete new coronavirus particles in the cells in the olfactory mucosa

In this regard, the neurobiologist Sandeep Robert Datta of Harvard University disagrees. His hypothesis is that the virus infection does not directly attack the nasal nerves, but is the support cells (sustentacular cells) that assist sensory neurons in the nose.

The hypothesis is based on the infectious characteristics of the new coronavirus. Studies have found that the new coronavirus binds to the ACE2 receptor on the cell surface during infection. The ACE2 receptor of the Sertoli cells in the nose is highly expressed, while the sensory neurons of the olfactory bulb are absent. This suggests that the new coronavirus may infect support cells to make neurons vulnerable to attack and undernourishment, which means that it destroys the “soil” of olfactory sensory neurons.

In addition, the new coronavirus may also cause olfactory disorders in patients in other ways. A study by an Italian team found that when the sense of smell and taste of patients with COVID-19 have problems at the same time, the level of inflammatory signaling molecule interleukin-6 in their blood will also increase. An anatomical study also showed that obvious signs of inflammation such as vascular leakage appeared in the olfactory bulb of the brain of patients with new coronavirusdisease.

Over the past year, the medical community has a certain understanding of the relevant mechanisms by which the COVID-19 affects the sense of smell, but the treatment plan for patients with olfactory disorders is still very thin. BMJ directly said that there is “no cure” for patients with inverted sense of smell.

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BMJ screenshot

Anosmia is a self-limiting disease for most people, and the sense of smell may be restored within a few weeks. According to a study, 72% of COVID-19 patients with olfactory dysfunction said that they had regained their sense of smell after a month. But for 10% of patients, this olfactory disorder is likely to not recover on its own or even become permanent loss of smell.

The BMJ has also pointed out that when the sense of smell is showing signs of recovery, patients often have obvious parosmia (parosmia). But can the sense of smell be restored? how much time is required? No one knows the answer.

At present, an olfactory training method is still recommended for patients with olfactory disorders caused by new coronavirus pneumonia. In the “Expert Consensus on the Diagnosis and Treatment of Olfactory Disorders” released in 2017, China pointed out the relevant definitions of olfactory training:

1. Olfactory training mainly uses 4 scents: phenylethyl alcohol (rose), eucalyptol (eucalyptus), citronellal (lemon), and eugenol (lilac)
2. Each smell is smelled for about 10 seconds, and there needs to be an interval of 10 seconds between smelling the two smells
3. The duration of each training session is 5 minutes
4. Train once every day before breakfast and before going to bed at night
5. It is recommended for patients with olfactory disorders to apply a variety of high-concentration pleasant substances with different odors for no less than 4 months of olfactory training

In Europe, the hardest hit area of ​​new coronavirus pneumonia, in addition to recommending the use of odor training, the expert team also proposed many different drugs such as oral corticosteroids, topical corticosteroids, zinc sulfate, α-lipoic acid, theophylline, carverine, vitamins A, Ginkgo biloba, sodium citrate and minocycline, etc.

However, there is currently limited evidence supporting the use of these drugs in the treatment of olfactory disorders, and there is no large randomized controlled trial (RCT) to confirm it.

First symptom to early diagnosis: smelling vinegar to argue the COVID-19?

At present, more than one study has found that the only early symptoms of many patients diagnosed with new coronavirus pneumonia are not fever and breathing problems, but malfunctions in the sense of smell and taste.

In China’s revised “New Coronavirus Pneumonia Diagnosis and Treatment Plan” (Trial Eighth Edition), it is clearly stated that some patients have diminished or lost sense of smell and taste as the first symptoms. The WHO has also listed loss of taste or smell as a symptom of new coronavirus pneumonia.

Some researchers suggest that olfactory failure should be used as a diagnostic criterion for new coronavirus pneumonia. A study in a Nature sub-Journal found that self-reports of smell or taste changes are more closely related to hospital overload and are a sign that reflects the spread of new coronavirus infection earlier than current government indicators.

As recently as November last year, a related literature on the Lancet even proposed that patients with asymptomatic infection can be accurately detected through quantitative assessment of patients’ olfactory dysfunction.

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Interestingly, this special detection method has already been used. According to Yonhap News Agency, in April last year, due to insufficient medical testing, the US military in South Korea also used a set of olfactory testing methods-smelling vinegar to screen people who may be infected with the new coronavirus.

(source:internet, reference only)

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