The mysterious loss of smell due to COVID-19 begins to clarify

We begin to have molecular explanations for this irritating but common symptom.

On a Saturday in early April last year, while sipping an infusion of fresh mint leaves, Eian Kantor realized that he had lost his sense of smell. She suspected it when she noticed that the tea didn’t smell of anything, so she rummaged in the fridge to sniff out a pot of pickles, a chili pepper sauce, and some garlic. But nothing.

Since New York State was confined in late March, 30-year-old Kantor and his girlfriend have been isolated in their Queens, New York apartment. So I did not even suspect that I could have COVID-19 despite a mild fever that he attributed to seasonal allergies. When she got tested weeks after her loss of smell (anosmia), she was negative. Months later, other tests indicated that he had antibodies against the new coronavirus “wildly high, confirming that he had passed the disease.”

It is estimated that 80 percent of people with COVID-19 have abnormalities in smell, and that many also have dysgeusia or ageusia (alteration or loss of taste, respectively), or changes in chemoesthesia (the ability to perceive irritating substances , like chillies). Loss of smell is so common in people with COVID-19 that some researchers have recommended using it as a diagnostic test, as it could be a more reliable marker than fever or other symptoms.

How the new coronavirus deprives its victims of these senses remains a mystery. At the beginning of the pandemic, doctors and researchers were concerned because they thought that COVID-19 anosmia indicated that the virus was making its way into the brain through the nose, where it would cause serious and lasting damage. It was suspected that the path would pass through olfactory neurons, which perceive odors in the air and transmit the signal to the brain. But the studies indicate that this is probably not the case, says Sandeep Robert Datta, a neuroscientist at Harvard Medical School. “All the data to date makes me think that the invasion really begins in the nose, in the nasal epithelium”, a layer of cells similar to the skin that is responsible for detecting odors. “It seems that the virus prefers to attack support cells and stem cells, but not neurons directly,” says Datta, and points out that this does not mean that neurons are not affected.

The surface of the olfactory neurons does not have the ACE2 receptor (angiotensin converting enzyme 2) that the virus uses to enter, while the support cells, which provide important support for the olfactory neurons in different ways, are dotted with them. These are the cells that maintain the delicate balance of saline ions in the mucus that neurons depend on to send signals to the brain. Any alteration of this balance would turn off neural signaling and with it smell.

Sustainability cells also provide the metabolic and physical support necessary to sustain the cilia emitted by olfactory neurons, where the receptors that detect odors are concentrated. According to Datta, “the physical alteration of these cilia causes loss of smell.”

Available tests

In a study by Nicolas Meunier, a neuroscientist at the University of Paris-Saclay, published in the journal Brain, Behavior and Immunity , the snouts of Syrian golden hamsters were infected with SARS-CoV-2. In two days, almost half of the support cells were infected, but not the olfactory neurons, even if two weeks had elapsed. What surprised Meunier was that the olfactory epithelium was completely detached, like the skin that peels off after a sunburn. Although the olfactory neurons were not infected, the cilia had completely disappeared. “The absence of cilia leads to the loss of olfactory receptors and the ability to detect aromas.”

The destruction of the olfactory epithelium could explain the loss of smell. It remains unclear whether the damage is done by the virus itself or by the invasion of immune cells that Meunier observed after infection. The abundance of reports of anosmia due to COVID-19 does not occur in other viral diseases. “We think it is very specific to SARS-CoV-2,” says Meunier. In a previous study of their laboratory with other respiratory viruses, they found that sustainable cells were not usually infected, while with SARS-CoV-2, almost half contained the pathogen. With other viruses, smell is often compromised by nasal congestion, but COVID-19 does not usually cause it. For Meunier, “it is very different.”

The researchers came up with a few clues to the loss of smell, but the mechanism by which the virus causes loss of taste is fraught with uncertainties. Flavor receptor cells detect chemicals in saliva and send the signal to the brain, but, according to a paper published last July, they do not contain ACE2, so they are unlikely to be infected with SARS-CoV- two. In contrast, other support cells in the tongue do carry the receptor, which may provide some clue to the disappearance of taste. Although the taste may seem to disappear with anosmia because odors are a key component of taste, many people with COVID-19 develop true ageusia and do not taste even sweet or salty.

Nor do we have an explanation, yet, for the loss of perception of other characters, such as the itchiness of chilli peppers or the refreshing sensation of mint. These sensations are not flavors, but their detection is transmitted through the body (including the mouth) by nerves that detect pain, some of which express ACE2.

Those recovering from anosmia are another source of explanations for the loss of smell due to the virus. According to Datta, “most patients lose their sense of smell as if a switch were turned off, and they regain it just as quickly. When the anosmia is much more persistent, recovery takes longer. The olfactory epithelium regenerates regularly. Meunier explains that “in this way the body is protected against the continuous avalanche of toxins that reach it from the environment.”

Even today, more than seven months after he first experienced anosmia, Kantor is one of the group of patients who still cannot smell anything at all. «It costs a lot, because you are not aware of how much you need smell until you lose it. If there was a fire in the house, I wouldn’t know about it. It worries me a lot. ” And, furthermore, anosmia takes away pleasure from food: “My favorite foods now don’t taste like anything to me.”

Carol Yan, a rhinologist at the University of California, San Diego, says that anosmia poses a real health risk. “It really increases mortality because if you don’t smell or taste food, you are exposed to harm, for example rotten food or a gas leak. It can also lead to social isolation or nutritional deficiencies. “

Sensory disturbances extend to another symptom called parosmia, a possible sign of recovery in people with long-lasting anosmia. This is the case of Freya Sawbridge, a 27-year-old New Zealander who fell ill with COVID-19 in March last year. After several weeks with anosmia and ageusia, when everything tasted like “ice cubes and cardboard”, Sawbridge began to recover the most basic flavors (sweet, salty and bitter), but no taste nuances from the aroma of food. “Chocolate tastes like sweet gum to me,” he says.

After about five months he recovered some smells, but not as expected: for a while, all the foods smelled like artificial raspberries and now “everything has a terrible and distorted smell. Nothing smells like it should and I find the aromas unpleasant. ” For Sawbridge, the smell of onions is unbearable, and a strange, artificial scent permeates everything. “All foods taste like they’ve been sprayed with glass cleaner to me.”

Parosmia may occur when newly generated stem cells that differentiate into neurons in the nose try to extend their long fibers, called axons, through tiny holes at the base of the skull to connect with the brain structure called the olfactory bulb. Sometimes axons connect to the wrong place and cause an erratic odor, although these misconnections usually self-correct after a sufficient time.

Recovery of smell

This news is great for people like Sawbridge. But the question you want an answer to is about how long your anosmia will last. According to Yan, “we do not know how long it will take for people with anosmia to recover,” but the normal is between six months and a year. “With long-term postviral anosmia due to the flu, the chance of spontaneous recovery after six months is between 30 and 50 percent” without any treatment. And he continues: «Cases have been described that recover after two years. After this period, we believe that the regenerative capacity could be inhibited, so, unfortunately, the possibility of recovery would be very remote ”.

Kantor has tried everything imaginable to regain his sense of smell: high-dose corticosteroid treatment to reduce inflammation; a smell training program with essential oils; b-carotene supplements for nerve regeneration; acupuncture … Nothing has made any difference. Yan recommends “flushing” the sinuses with budesonide, a topically administered corticosteroid shown to improve outcomes in a Stanford University study of patients who lost their sense of smell for more than six months after the flu . Other treatment Promising that Yan and his colleagues are investigating is platelet-rich plasma, an anti-inflammatory preparation isolated from blood that has been used to treat some types of nerve damage. But Yan says that regardless of treatment, the results “are not sensational. No one is going to get up noticing that they smell again. But if you smell soap again or enjoy the taste of some foods, you have gained a lot. “

And one final worrying note about anosmia: It has been determined to be a risk factor for some neurodegenerative diseases. Meunier informs us that “after the pandemic flu of 1919 we saw an increase in the prevalence of Parkinson’s disease. It would be really disturbing if something similar happened now.

But Yan thinks this fear is exaggerated: “There is certainly a connection between anosmia and disease, but we believe that virus-induced anosmia occurs by a very different mechanism. That we have postviral anosmia does not imply that the risk for other diseases is greater, because they are two completely independent phenomena. This should reassure Sawbridge and Kantor, as well as the millions of people around the world affected by COVID-19-related anosmia.