It was the juice that warned him. At lunch, Icarus from AT Pires found the taste of his grape juice, flattened in sugar water, dull. There was no grape goodness. “I stopped eating lunch and went to the bathroom to try to smell the toothpaste and shampoo,” says Pires, an otolaryngologist at IPO Hospital in Curitiba, Brazil. “Then I realized I couldn’t smell anything.”
Pires had been showing symptoms of COVID-19 for about three days when his sense of smell vanished, an absence that left a mark on his days. On a trip to the beach two months later, he couldn’t smell the sea. “This was always a scent that brought back good memories and feelings,” says Pires. “The fact that I didn’t feel it made me realize how many things in my day weren’t as fun as they used to be. Smell can connect with our emotions like no other sense can.”
When SARS-CoV-2, the virus responsible for COVID-19, swept the world, it robbed millions of people of their sense of smell, leaving them with a condition called anosmia. Early in the pandemic, when Pires juice turned to water, that olfactory theft became one of the quickest ways to signal a COVID-19 infection. Over time, most people who have lost their sense of smell regain their senses. Pires, meanwhile, has gradually recovered much of his sense of smell. But that is not the case for everyone.
About 5.6 percent of people with post-COVID-19 loss of smell (or the closely related loss of taste) still cannot smell or taste normally six months later, suggests a recent analysis of 18 studies. The number, reported on July 30 British medical journalit seems small. But when considering the estimated 550 million cases and tally of COVID-19 worldwide, it adds up.
Scientists are looking for ways to speed up olfactory healing. Three years into the COVID-19 pandemic, researchers have a better idea of how many people are affected and how long it appears to last. However, when it comes to ways to rewire the sense of smell, the state of science is not promising.
A method called olfactory training, or smell training, has shown promise, but big questions remain about how it works and for whom. The technique has been around for a while; the coronavirus is not the first ailment to take away the smell. But with new pressure from people affected by COVID-19, smell training and a host of other newer treatments are now getting much more attention.
The pandemic has drawn attention to the loss of smell. “If we are to provide a silver lining, COVID is driving science forward at a speed that has never happened before,” says Valentina Parma, an olfactory researcher and deputy director of the Monell Chemical Senses Center in Philadelphia. “But,” she warns, “we are really far from a solution.”
nose attack
Compared to sight or hearing, the sense of smell can seem like an afterthought. But losing it can deeply affect people. “Your world really changes if you lose your sense of smell, in ways that are often worse,” says Parma. The smell of a baby’s head, a buttery curry, or the sharp, salty sea can add emotional meaning to experiences. Odors can also warn of danger, such as the rotten egg smell that indicates a natural gas leak.
As an ENT doctor, Pires recalls a deaf patient who lost her sense of smell after COVID-19 and was enrolled in a clinical trial he and his colleagues conducted on smell training. He worked in a perfume company: her sense of smell was crucial to her work and his life. “On the first date, she told her, with tears in her eyes, that she felt like she didn’t live,” recalls Pires.
Unlike the cells that detect color or sound, the cells that sense smell can be replenished. Stem cells in the nose are constantly pumping out new cells that are sensitive to smell. Called olfactory sensory neurons, these cells are dotted with molecular networks that hook onto specific odor molecules floating around in the nose. Once activated, these cells send messages through the skull and to the brain.
Due to their nasal proximity, olfactory sensory neurons are exposed to environmental hazards. “They may be covered in a little layer of mucus, but they’re sitting out there being constantly bombarded with bacteria, viruses and contaminants and who knows what else,” says Steven Munger, a chemosensory neuroscientist at the University of Florida School of Medicine. in Gainesville.
Exactly how SARS-CoV-2 damages the olfactory system is unclear. But recent studies suggest that the virus attack is indirect. The virus can infect and kill supporting cells in the nose called sustainacular cells, which are thought to help keep olfactory neurons happy and fueled by delivering glucose and maintaining the proper balance of salt. That attack can inflame the olfactory epithelium, the layers of cells that line parts of the nasal cavity.
Once this tissue is irritated, the olfactory sensory neurons Get nervous, even though the cells themselves have not been attacked. After an infection and subsequent inflammation, these neurons slow down the output of their odor-capturing networks, a slowdown that could blind them to odor molecules, the scientists report in the March 17 issue. Cell.
Over time, the inflammation stabilizes and the olfactory sensory neurons can return to their usual jobs, the researchers suspect. “We think that for post-viral olfactory disorders, the most common way to regain function is going to be spontaneous recovery,” says Munger. But in some people, this process doesn’t happen quickly, if at all.
That’s where smell training comes in.
A nose workout
One of the only therapies out there, smell training is pretty simple: good old-fashioned nose training. It involves deeply smelling four scents (usually rose, eucalyptus, lemon, and clove) for 30 seconds each, twice a day for months.
In one study, 40 people with smell disorders came out of training with enhanced smelling abilitieson average, compared to 16 people who didn’t get the training, olfactory researcher Thomas Hummel and colleagues reported in March 2009. Laryngoscope.
Since then, most studies have shown that the method helps between 30 percent and 60 percent of people who try it, says Hummel, of the Technische Universität Dresden in Germany. His opinion is that the method can help some people, “but it doesn’t work for everyone.”
One of the good things is that there are no harmful side effects, says Hummel. That’s “the charming side of it.” But getting the workout right requires discipline and stamina. “If you don’t do it regularly and give up after 14 days, this is useless,” he says.
At his recent trial, Pires hoped to speed up the process, which usually takes three months, by adding four more scents to the regimen. Over four weeks, 80 participants received four or eight scents. Both groups improved, but there was no difference between the two groupsthe researchers reported on July 21 in the American journal of rhinology and allergy.
It is not known how the technique works in the people it seems to help. It may be that it focuses people’s attention on faint odors; it could be stimulating the growth of replacement cells; it could be strengthening some pathways in the brain. Data from other animals suggests that such training can increase the number of olfactory sensory neurons, says Hummel.
Overall, this nose boot camp may be a possible approach for people to try, but big questions remain about how it works and for whom, says Munger. “In my view, it’s very important to be honest with patients about the very real possibility that this therapy may not lead to a restoration of smell, even if they and their doctor feel it’s worth trying,” she says. “I’m not trying to discourage people here, but I also think we have to be very careful not to make unwarranted promises.”
Smell training has no harmful biological side effects, but it can lead to frustration if it doesn’t work, says Parma. In her practice, “I’ve been talking to a lot of people who say, ‘I did this every day for six months, twice a day for 10 minutes. I got together in groups with other people, so we held each other accountable, and I did that for six months. And it didn’t work for me.’” She adds, “I would like to address the frustration this causes for patients.”
beyond training
Other potential treatments are under scrutiny, including steroids, omega-3 supplements, growth factors, and vitamins A and E, all of which could stimulate the recovery of the nasal epithelium.
More futuristic remedies are also in the early stages of research. These include epithelial transplants designed to stimulate olfactory stem cells, platelet-rich plasma treatments to curb inflammation and promote healing, and even an “electronic nose” that would detect odor molecules and stimulate the brain directly. This cyborg-scented system is inspired by cochlear implants for hearing and retinal implants for vision.
For many people, the sense of smell is appreciated only after it’s gone, says Parma, an apathy that is illustrated in stark terms in a recent study of some 400 people. The vast majority of those surveyed, nearly 85 percent, would rather give up their sense of smell than sight or hearing. About 19 percent of those surveyed said they would rather give up their sense of smell than their cell phone. The survey results “dramatically illustrate the insignificant value people attribute to their sense of smell,” the researchers wrote in the March issue brain science.
Even as a doctor who treats people with loss of smell, Pires has a newfound fondness for a good puff. “Having lost him for a while made me appreciate him even more.”