It was the juice that tipped him off. At lunch, \u00cdcaro de A.T. Pires found the flavor of his grape juice muted, flattened into just water with sugar. There was no grape goodness. \u201cI stopped eating lunch and went to the bathroom to try to smell the toothpaste and shampoo,\u201d says Pires, an ear, nose and throat specialist at Hospital IPO in Curitiba, Brazil. \u201cI realized then that I couldn\u2019t smell anything.\u201d<\/p>\n\n\n\n
Pires was about three days into COVID-19 symptoms 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\u2019t smell the sea. \u201cThis was always a smell that brought me good memories and sensations,\u201d Pires says. \u201cThe fact that I didn\u2019t feel it made me realize how many things in my day weren\u2019t as fun as before. Smell can connect to our emotions like no other sense can.\u201d
As SARS-CoV-2, the virus responsible for COVID-19, ripped across the globe, it stole the sense of smell away from millions of people, leaving them with a condition called anosmia. Early in the pandemic, when Pires\u2019 juice turned to water, that olfactory theft became one of the quickest ways to signal a COVID-19 infection. With time, most people who lost smell recover the sense. Pires, for one, has slowly regained a large part of his sense of smell. But that\u2019s not the case for everyone.<\/p>\n\n\n\n
About 5.6 percent of people with post\u2013COVID-19 smell loss (or the closely related taste loss) are still <\/a>not able to smell or taste normally six months later<\/a>, a recent analysis of 18 studies suggests. The number, reported in the July 30 British Medical Journal<\/em>, seems small. But when considering the estimated 550 million cases and counting of COVID-19 around the world, it adds up.<\/p>\n\n\n\n Scientists are searching for ways to hasten olfactory healing. Three years into the COVID-19 pandemic, researchers have a better idea of how many people are affected and how long it seems to last. Yet when it comes to ways to rewire the sense of smell, the state of the science isn\u2019t coming up roses.<\/p>\n\n\n\n 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 isn\u2019t the first ailment to snatch away smell. But with newfound pressure from people affected by COVID-19, olfactory training and a host of other newer treatments are now getting a lot more attention.<\/p>\n\n\n\n The pandemic has brought increased attention to smell loss. \u201cIf we have to provide a silver lining, COVID is pushing the science at a speed that\u2019s never happened before,\u201d says Valentina Parma, an olfactory researcher and assistant director of the Monell Chemical Senses Center in Philadelphia. \u201cBut,\u201d she cautions, \u201cwe are really far from a solution.\u201d<\/p>\n\n\n\n Compared with sight or hearing, the sense of smell can seem like an afterthought. But losing it can affect people deeply. \u201cYour world really changes if you lose the sense of smell, in ways that are usually worse,\u201d Parma says. The smell of a baby\u2019s head, a buttery curry or the sharp salty sea can all add emotional meaning to experiences. Smells can also warn of danger, such as the rotten egg stench that signals a natural gas leak.<\/p>\n\n\n\n As an ear, nose and throat doctor, Pires recalls a deaf patient who lost her sense of smell after COVID-19 and enrolled in a clinical trial that he and colleagues conducted on smell training. She worked in a perfumery company \u2014 her sense of smell was crucial to her job and her life. \u201cAt the first appointment, she said, with tears in her eyes, that it felt like she wasn\u2019t living,\u201d Pires recalls.<\/p>\n\n\n\n Unlike the cells that detect color or sound, the cells that sense smell can replenish themselves. Stem cells in the nose are constantly pumping out new smell-sensing cells. Called olfactory sensory neurons, these cells are dotted with molecular nets that snag specific odor molecules that waft into the nose. Once activated, these cells send messages through the skull and into the brain.<\/p>\n\n\n\n Because of their nasal neighborhood, olfactory sensory neurons are exposed to the hazards of the environment. \u201cThey may be covered with a little layer of mucus, but they\u2019re sitting out there being constantly bombarded with bacteria and viruses and pollutants and who knows what else,\u201d says Steven Munger, a chemosensory neuroscientist at the University of Florida College of Medicine in Gainesville.<\/p>\n\n\n\n Exactly how SARS-CoV-2 damages the smell system isn\u2019t clear. But recent studies suggest the virus\u2019s assault is indirect. The virus can infect and kill nose support cells called sustentacular cells, which are thought to help keep olfactory neurons happy and fed by delivering glucose and maintaining the right salt balance. That attack can inflame the olfactory epithelium, the layers of cells that line parts of the nasal cavity.<\/p>\n\n\n\n Once this tissue is riled up, the olfactory sensory neurons <\/a>get wonky<\/a>, even though the cells themselves haven\u2019t been attacked. After an infection and ensuing inflammation, these neurons slow down the production of their odor-catching nets, a decrease that could blind themselves to odor molecules, scientists reported in the March 17 Cell<\/em>.<\/p>\n\n\n\n With time, the inflammation settles down, and the olfactory sensory neurons can get back to their usual jobs, researchers suspect. \u201cWe do think that for post-viral smell disorders, the most common way to recover function is going to be spontaneous recovery,\u201d Munger says. But in some people, this process doesn\u2019t happen quickly, if ever.<\/p>\n\n\n\n That\u2019s where smell training comes in.<\/p>\n\n\n\n One of the only therapies that exists, smell training is quite simple \u2014 a good old-fashioned nose workout. It involves deeply smelling four scents (usually rose, eucalyptus, lemon and cloves) for 30 seconds apiece, twice a day for months. <\/p>\n\n\n\n In one study, 40 people who had smell disorders came away from the training with improved smelling abilities<\/a>, on average, compared with 16 people who didn\u2019t do the training, olfactory researcher Thomas Hummel and his colleagues reported in the March 2009 Laryngoscope<\/em>.<\/p>\n\n\n\n Since then, the bulk of studies has shown that the method helps between 30 and 60 percent of the people who try it, says Hummel, of Technische Universit\u00e4t Dresden in Germany. His view is that the method can help some people, \u201cbut it does not work in everybody.\u201d<\/p>\n\n\n\n One of the nice things is that there are no harmful side effects, Hummel says. That\u2019s \u201cthe charming side of it.\u201d But to do the training correctly takes discipline and stamina. \u201cIf you don\u2019t do it regularly, and you give up after 14 days, this is futile,\u201d he says.<\/p>\n\n\n\n Pires in his recent trial had hoped to speed up the process, which usually takes three months, by adding four more odors to the regimen. For four weeks, 80 participants received either four or eight smells. Both groups improved, but <\/a>there was no difference between the two groups<\/a>, the researchers reported July 21 in the American Journal of Rhinology & Allergy<\/em>.<\/p>\n\n\n\n It\u2019s not known how the technique works in the people it seems to help. It could be that it focuses people\u2019s attention on faint smells; it could be stimulating the growth of replacement cells; it could be strengthening some pathways in the brain. Data from other animals suggest that such training can increase the number of olfactory sensory neurons, Hummel says.<\/p>\n\n\n\n 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, Munger says. \u201cIn my view, it\u2019s very important to be up front with patients about the very real possibility this therapy may not lead to a restoration of smell, even if they and their doctor feel it is worth trying,\u201d he says. \u201cI am not trying to discourage people here, but I also think we need to be very careful not to give unwarranted promises.\u201d <\/p>\n\n\n\n Smell training doesn\u2019t come with harmful biological side effects, but it can induce frustration if it doesn\u2019t work, Parma says. In her practice, \u201cI have been talking to a lot of people who say, \u2018I did it every day for six months, twice a day for 10 minutes. I met in groups with other people, so we kept each other accountable, and I did that for six months. And it didn\u2019t work for me.\u2019\u201d She adds, \u201cI would want to address the frustration that this induces in patients.\u201d<\/p>\n\n\n\n Other potential treatments are coming under scrutiny, such as steroids, omega-3 supplements, growth factors and vitamins A and E, all of which might encourage the recovery of the nasal epithelium.<\/p>\n\n\n\n More futuristic remedies are also in early stages of research. These include epithelial transplants designed to boost olfactory stem cells, treatments with platelet-rich plasma to curb inflammation and promote healing, and even an \u201celectronic nose\u201d that would detect odor molecules and stimulate the brain directly. This cyborg-smelling system takes inspiration from cochlear implants for hearing and retinal implants for vision. <\/p>\n\n\n\n People routinely undervalue the sense of smell. Some people rated the ability to smell as less important than various creature comforts, hair and even the little left toe, a recent survey found.<\/p>\n\n\n\n For many people, the sense of smell is appreciated only after it\u2019s gone, Parma says, an apathy that\u2019s illustrated in stark terms by a recent study of about 400 people. The vast majority of respondents \u2014 nearly 85 percent \u2014 would rather give up their sense of smell than sight or hearing. About 19 percent of respondents said they would prefer to give up their sense of smell than their cell phone. The survey results \u201cdramatically illustrate the negligible value<\/a> people place on their sense of smell,\u201d researchers wrote in the March Brain Sciences<\/em>.<\/p>\n\n\n\n Even as a doctor who treats people with smell loss, Pires has a newfound fondness for a good whiff. \u201cHaving lost it for a while made me appreciate it even more.\u201d <\/p>\n\n\n\n B.K.J. Tan et al<\/em>. Prognosis and persistence of smell and taste dysfunction in patients with COVID-19: meta-analysis with parametric cure modelling of recovery curves<\/a>. The British Medical Journal<\/em>. Vol. 378, July 30, 2022. doi:10.1136\/bmj-2021-069503.<\/p>\n\n\n\n M. Zazhytska et al<\/em>. Non\u2013cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19\u2013induced anosmia<\/a>. Cell<\/em>. Vol. 185, March 17, 2022, p. 1052. doi: 10.1016\/j.cell.2022.01.024.<\/p>\n\n\n\n T. Hummel et al<\/em>. Effects of olfactory training in patients with olfactory loss<\/a>. Laryngoscope<\/em>. Vol. 119, March 2009, p. 496. doi: 10.1002\/lary.20101.<\/p>\n\n\n\n \u00cd. de A.T. Pires et al<\/em>. Intensive olfactory training in post\u2013COVID-19 patients: a multicenter randomized clinical trial<\/a>. American Journal of Rhinology & Allergy<\/em>. Published online July 21, 2022. doi: 10.1177\/19458924221113124.<\/p>\n\n\n\nNasal attack<\/h4>\n\n\n\n
A nose workout<\/h4>\n\n\n\n
Beyond training<\/h4>\n\n\n\n
Selling smell short<\/h3>\n\n\n\n
How many people would rather give up smell than these things:<\/h6>\n\n\n\n
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