A treatment for COVID-19 survivors who have lost their sense of smell is ‘olfactory training’, in which they relearn the prescribed aromas, such as roses and lemons.Credit: Christine E. Kelly
At the beginning of the COVID-19 pandemic, it was found that many people infected with the SARS-CoV-2 virus were losing their sense of smell – even without showing other symptoms. The researchers also found that infected people can lose their taste and the ability to detect chemically triggered sensations, such as the spicy taste, called chemesthesia.
Almost a year later, some have not yet recovered those senses, and for a proportion of people who have recovered them, odors are now distorted: unpleasant odors have replaced normally delicious ones. Nature researches the science behind this potentially lasting and debilitating phenomenon.
How many people with COVID-19 lose their sense of smell?
The exact percentage varies between studies, but most suggest that loss of smell is a common symptom.
A review published last June1 compiled data from 8,438 people with COVID-19 and found that 41% reported having lost sense of smell. In another study, published in Augusttwo, a team led by researcher Shima T. Moein of the Fundamental Sciences Research Institute in Tehran, Iran, administered an odor identification test on 100 people with COVID-19, in which the subjects sniffed odors and identified them in a multiple choice base. Ninety-six percent of participants had some olfactory dysfunction and 18% had total loss of smell (also known as anosmia).
“Typically, these patients say they have suddenly lost their smell,” a clue that the symptom is related to COVID-19, says Moein. And often, dysfunction is the only symptom of COVID-19 that people register, suggesting that the phenomenon is separate from virus-induced nasal congestion.
Some researchers claim that loss of smell should be used as a diagnostic test for COVID-19. A study published last October3 found that self-reported changes in smell or taste were a better marker for the spread of infection than other indicators monitored by governments, such as accident arrivals at hospitals and emergency departments.
Why do people with COVID-19 lose their sensitivity to smells?
Although the mechanisms are not fully understood, there is an emerging consensus that loss of smell occurs when the coronavirus infects the cells that support neurons in the nose.
When researchers first identified loss of smell as a symptom of COVID-19, they were concerned that the virus was infecting the odor-detecting neurons in the nose that send signals to the olfactory bulb in the brain – and that the virus could, therefore, access the brain. However, post-mortem studies4 of people who have had COVID-19 have shown that the virus rarely reaches the brain.
A team led by Sandeep Robert Datta, a neurobiologist at Harvard Medical School in Boston, Massachusetts, discovered5 that the cells that support sensory neurons in the nose – known as sustaining cells – are probably what the virus is infecting.
Datta and his colleagues focused on sustaining cells because SARS-CoV-2 attacks targeting a receptor called ACE2 on the surface of cells, and sustaining cells have many of these receptors. Olfactory sensory neurons do not. This suggests that the coronavirus infects support cells, leaving neurons vulnerable and deprived of nutrients.
But there may be other ways in which COVID-19 induces smell loss. For example, a research team in Italy showed6 this loss of smell and taste occurs at the same time as an increase in blood levels of an inflammation-signaling molecule called interleukin-6. And a post-mortem study published last December showed clear signs of inflammation, like leaking blood vessels, in the olfactory bulbs of people who had COVID-197.
Although scientists have some understanding of the mechanisms involved in smell, they have little idea about how the coronavirus affects taste and chemesthesia. “As far as I know, nobody really knows that,” says John Hayes, a professor of food science at Pennsylvania State University at University Park, who is studying the effects of COVID-19 on the chemical senses. Taste and chemesthesia are different senses of smell, although the three combine to tell humans what the “taste” of a food or drink is. Taste depends mainly on taste receptors on the tongue, while chemotherapy is based on ion channels in the sensory nerves, among other mechanisms – and its response to COVID-19 has not been studied much.
How quickly do the impaired senses return?
For most people, smell, taste and chemesthesia recover within weeks. In a study published last July8, 72% of people with COVID-19 who had olfactory dysfunction reported that they recovered their sense of smell after one month, as well as 84% of people with impaired taste. Claire Hopkins, an ear, nose and throat consultant at Guy’s and St Thomas’ Hospital in London, UK, and colleagues observed similarly9 a quick return of the senses: they followed 202 patients for a month and found that 49% reported complete recovery over that time, and another 41% reported an improvement.
But for others, the symptoms are more severe. Some people whose senses do not return immediately improve slowly over a long period – and that can have consequences, says Hopkins. As a person regains his sense of smell, odors are often recorded as unpleasant and different from how he remembered them, a phenomenon called parosmia. “Everything smells rancid” to these people, says Hopkins, and the effect can last for months. This may be because the olfactory sensory neurons are rewiring as they recover, she says.
Other patients remain fully anosmático for months, and it is not clear why. Hopkins suggests that in these cases, coronavirus infection may have killed the olfactory sensory neurons.
How does the permanent loss of chemical senses affect a person?
Although the condition is not as well studied as the loss of other senses, such as vision and hearing, the researchers know that the consequences can be serious.
One effect is that it leaves people vulnerable to dangers such as food poisoning and fire. For example, people with anosmia are less able to detect bad food and smoke. A 2014 study found that people with anosmia were more than twice as likely to experience a dangerous event, such as eating spoiled food, than people with no loss of smell10.
Other effects are more difficult to measure. “Most people don’t recognize the importance of smell in their lives – until they lose it,” says Moein. Being unable to enjoy the taste of food is obviously a big loss, but other sensations are also important. Hayes points, for example, to the loss that a father would feel if he could not connect with his son through the “smell of a newborn baby”. And Moein says that smell dysfunction has been linked to depression, although the biological mechanism involved is unclear.
Are there treatments available to restore these senses?
The lack of research means that there are few established treatments. But one option is the training of smell, in which people smell the odors prescribed regularly to relearn them. Hopkins is working with a charity called AbScent in Andover, UK, to publicize this training to the public. There is evidence11 since before the pandemic it can improve the sense of smell in some people with such disabilities, but it doesn’t seem to work for everyone.
The drugs available are even more limited, says Hopkins. But for people in the early stages of COVID-19 infection, when the loss of smell can be largely due to inflammation of the nose’s cells, steroids can be useful, according to a preliminary trial conducted by Hopkins’s team12.
In long-term research, Richard Costanzo and Daniel Coelho of Virginia Commonwealth University in Richmond are developing an olfactory implant – a device embedded in the nose that detects odorous chemicals and sends electrical signals to the brain. However, the device is still “many years” to be offered in clinics, says Coelho. In particular, researchers need to find out which areas of the brain the implant should stimulate, he adds, so “there is still a little science to discover”.