How Covid-19 causes loss of smell

One Saturday morning in early April, while preparing fresh mint leaves, Eian Kantor noticed that he had lost his sense of smell: strangely, his herbal tea did not smell at all. . He started rummaging in the refrigerator and smelling a jar of pickles, hot sauce, garlic: no smell.

From the start of his New York State imprisonment in late March, Eian Kantor, 30, had been locked up with his partner in his apartment in Queens, New York. He therefore did not suspect he had Covid-19, despite a mild fever that he attributed to seasonal allergies. When he was finally able to take the test several weeks after he lost his sense of smell – or anosmia – the test came back negative. But months later, several other tests showed he had high levels of antibodies to the new coronavirus, which confirmed he was infected.

It is estimated that around 80% of people with Covid-19 suffer from odor disorders and many of them also suffer from dysgeusia or ageusia (a taste disorder or loss, respectively) or changes in the ability to detect irritants such as chili pepper. Loss of smell is so common in people infected with the coronavirus that some researchers have recommended its use as a diagnostic test because it may be a more reliable marker of fever or other symptoms.

But a mystery persists: how does SARS-CoV-2 (the virus responsible for Covid-19) deprive its victims of their smell and taste? At the start of the pandemic, doctors feared that anosmia could signal that the virus was making its way to the brain, where it could cause serious and lasting damage. through the olfactory neurons present in the nose. But studies have shown that this probably isn’t the case, says Sandeep Datta, a neuroscientist at Harvard University School of Medicine. “An exhaustive reading of the data available to date suggests that the main damage is in fact located in the nose, in the nasal epithelium”, the layer of cells responsible for the registration of odors. “It appears that the virus mainly attacks supporting cells and stem cells and not neurons directly,” explains Sandeep Datta. But that doesn’t mean the neurons can’t be affected, he says.

Olfactory neurons have no ACE2 receptors (for the angiotensin converting enzyme) on their surface, which allow SARS-CoV-2 to enter cells. But the so-called “sustentacular” cells, which support and protect olfactory neurons, are studded with ACE2 receptors. These cells maintain, in the mucus that lines the olfactory epithelium, the delicate ionic balance necessary for olfactory neurons to generate signals for the brain. If this balance is disturbed, it can lead to the arrest of neural signaling and therefore of the sense of smell. The sustentacular cells also provide metabolic and mechanical support to the cilia located at the ends of the olfactory neurons, on which odor-detecting receptors are concentrated. “If something physically interrupts these lashes, it affects the ability to smell,” says Sandeep Datta.

In a study published in early July in Brain, behavior and immunity, Nicolas Meunier, of the University of Paris-Saclay, infected the nose of hamsters with SARS-CoV-2. Two days later, about half of the rodent tissue cells were infected. But the olfactory neurons were spared, even after two weeks. And, surprisingly, the olfactory epithelium of the hamsters was completely detached, just like the peeling skin after sunburn, according to Nicolas Meunier. Although the olfactory neurons weren’t infected, their cilia had completely disappeared. “But if you remove the lashes, you remove the olfactory receptors and therefore the ability to detect odors,” explains Nicolas Meunier.

The degradation of the olfactory epithelium could explain the loss of smell. But it is still unclear whether the damage is caused by the virus itself or by an invasion of immune cells, which Nicolas Meunier observed after the infection. One thing is certain: there are not as many cases of anosmia in other viral diseases. “We think this is a very specific symptom of SARS-CoV-2,” says Nicolas Meunier. In previous work on other respiratory viruses in his lab, he found that sustentacular cells were only rarely infected, while in the case of SARS-CoV-2, about half of those cells contained the pathogen. In other viral infections, the sense of smell is often disturbed by a stuffy nose, but Covid-19 does not usually cause nasal congestion.

Therefore, the researchers found compelling explanations for the loss of smell. The origin of the loss of taste, however, remains more uncertain. Of course, we can have the impression of losing taste when we become anosmic, since smells are a fundamental component of flavors (all the sensations perceived during the tasting of a food). But many people with Covid-19 develop true ageusia and cannot even detect sweet or salty taste. Taste receptor cells, which detect compounds in saliva and send signals to the brain, do not have an ACE2 receptor and are therefore unlikely to be infected with SARS-CoV-2. But other supporting cells in the tongue carry this receptor, which can indicate a clue to the disappearance of taste.

Even the loss of “thermal” perception – the hot pepper sting or the refreshing sensation of mint – remains inexplicable and largely unexplored. These sensations are not tastes. Rather, their detection is transmitted by pain-sensitive nerves, some of which have ACE2 receptors, found throughout the body, including the mouth.

Other clues to how the coronavirus makes odors go away come from people recovering from anosmia. “Most patients suddenly lose their smell and recover it quickly, but some have much more persistent anosmia and regain their sense of smell over much longer time scales,” says Sandeep Datta. The olfactory epithelium regenerates itself regularly, “a protection against the constant aggression of toxins present in the environment”, specifies Nicolas Meunier.

Eian Kantor belongs to the second group of patients: more than seven months after his loss of smell, he still does not smell any. “It is difficult to live with it. You don’t realize how important the smell is until it’s gone. If there was a fire in my house, I wouldn’t even hear it. It is very worrying ”, explains the young man. And then the anosmia reduces the pleasure of eating to nothing. “The foods I once loved now taste tasteless and disgusting,” he adds.

According to Carol Yan, a rhinologist at the University of California at San Diego, anosmia is a real health risk. “Mortality increases. If you can’t smell and taste food, it exposes you to dangers, such as poisoning. Anosmia can also lead to social handicaps or nutritional deficiencies. “

This variation on the sensory theme extends to another symptom called “parosmia,” a sign of potential recovery in people with prolonged anosmia. Freya Sawbridge, a 27-year-old New Zealander, contracted Covid-19 in March. After several weeks of anosmia and ageusia, during which everything smelled of “ice cubes and cardboard”, the young woman began to find the most basic tastes – sweet, salty, sour – but no nuances of aromas. that come from food. “The chocolate tasted like sweet gum,” he says.

Then after about five months some odors returned, but not as expected. For a while, all the food smelled of an artificial strawberry flavor. But today “everything smells bad and is wrong,” says Freya Sawbridge. No smell is constant and all are unpleasant. The smell of onions is unbearable and a strange “chemical taste” permeates everything. “Everything I eat seems to have been sprayed with a window cleaner,” he adds.

Parosmia can occur when stem cells developing into new olfactory neurons attempt to project their long fibers, called “axons,” through tiny holes at the base of the skull and then connect to a structure in the brain called the bulb. olfactory “. Sometimes the axons connect in the wrong place causing the wrong smell, but over time the wrong wiring is potentially able to correct itself.

This is good news for patients like Freya Sawbridge. But, like others, he wants to know how long his anosmia will last. “We can’t predict the exact recovery time for people with anosmia,” replies Carol Yan, but it’s typically six months to a year. “In persistent loss of smell from the flu, after six months there is a 30-50% chance of spontaneous recovery,” he adds. There have been cases of healing after two years. But we believe that the ability to regenerate may also be hampered. And the chances of recovery are unfortunately rather slim. “

Eian Kantor has tried every conceivable way to regain his sense of smell: a high-dose steroid course to reduce inflammation, an olfactory training program with essential oils, beta-carotene supplements for nerve regeneration, and acupuncture. Nothing made a difference. Carol Yan recommends breast irrigation with budesonide, a topical steroid that a Stanford University study showed better results in people who have lost their sense of smell for more than six months after the flu. Another promising treatment Carol Yan and other researchers are studying is platelet-rich plasma, a fluid with anti-inflammatory properties extracted from the blood that has been used to treat certain types of nerve damage. But regardless of the treatment, “the results aren’t great,” says Carol Yan. It’s not like you wake up saying to yourself “I smell the smell again!” But if you can smell soap again or appreciate the taste of certain foods, that’s a big step forward. “

There is a final worrying aspect of anosmia: it has been identified as a risk factor for some neurodegenerative diseases. “After the so-called ‘Spanish’ flu pandemic of 1919, there has been an increase in the prevalence of Parkinson’s disease, explains Nicolas Meunier. It would be really worrying if something similar happened with Covid-19. “

But Carol Yan thinks this fear is exaggerated. “There is certainly a link between classical anosmia and neurodegenerative diseases, but we believe that viral infection-induced anosmia works by a completely different mechanism,” he says. These viral anosmias probably do not increase the risk of neurodegenerative diseases. This should reassure Freya Sawbridge and Eian Kantor, as well as the millions of others around the world affected by Covid-19-related loss of smell.