Many COVID-19 patients lost their sense of smell. Will they get it back?

While scientists work to unravel the basic biology of the nose, some patients are finding positive effects from smell training.

By Sara Harrison
Published 7 Aug 2020, 12:00 BST, Updated 5 Nov 2020, 04:57 GMT
A health worker administers an olfactory test to monitor smell loss to a resident in the ...

A health worker administers an olfactory test to monitor smell loss to a resident in the Altos de San Lorenzo neighborhood near the city of La Plata, Argentina, on May 24, 2020.

Photograph by Alejandro Pagni, AFP via Getty Images

In early March, Peter Quagge began experiencing COVID-19 symptoms, such as chills and a low-grade fever. As he cut pieces of raw chicken to cook for dinner one night, he noticed he couldn’t smell the meat. “Must be really fresh,” he remembers thinking. But the next morning he couldn’t smell the Dial soap in the shower or the bleach he used to clean the house. “It sounds crazy, but I thought the bleach had gone bad,” he says. When Quagge stuck his head into the bottle and took a long whiff, the bleach burned his eyes and nose, but he couldn’t smell a thing.

The inability to smell, or anosmia, has emerged as a common symptom of COVID-19. Quagge was diagnosed with COVID-19, though he was not tested, since tests were not widely available at the time. He sought anosmia treatment with multiple specialists and still has not fully recovered his sense of smell.

Case reports suggest that anywhere between 34 and 98 percent of hospitalised patients with COVID-19 will experience anosmia. One study found that COVID-19 patients are 27 times more likely than others to lose their sense of smell, making anosmia a better predictor of the illness than fever.

For most COVID-19 patients who suffer anosmia, the sense returns within a few weeks, and doctors don’t yet know if the virus causes long-term smell loss. While not being able to smell may sound like a small side effect, the results can be devastating. The sense is intricately tied up in self-preservation—the ability to smell fire, chemical leaks, or spoiled food—and in our ability to pick up on complex tastes and enjoy food.

So many of the ways we connect with each other is over meals or over drinks,” says Steven Munger, director of the Centre for Smell and Taste at the University of Florida. “If you can’t fully participate in that, it creates a sort of social gap.”

Smell even plays a role in our emotional lives, connecting us to loved ones and memories. People without smell often report feeling isolated and depressed and losing their enjoyment in intimacy. Now scientists are starting to unravel how COVID-19 affects this critical sense, hoping those discoveries will help thousands of newly anosmic people looking for answers.

What the nose knows

The olfactory system, which allows humans and other animals to smell, is essentially a way of decoding chemical information. When someone takes a big sniff, molecules travel up the nose to the olfactory epithelium, a small piece of tissue at the back of the nasal cavity. Those molecules bind to olfactory sensory neurons, which then send a signal by way of an axon, a long tail that threads through the skull and delivers that message to the brain, which registers the molecules as, say, coffee, leather, or rotting lettuce.

Scientists still don’t fully understand this system, including exactly what happens when it stops working. And most people don't realise how common smell loss really is, Munger says. “That lack of public understanding means there’s less attention to try to understand the basic functions of the system.”

People can lose their sense of smell after suffering a viral infection, like influenza or the common cold, or after a traumatic brain injury. Some are born without any sense of smell at all or lose it because of cancer treatments or diseases like Parkinson’s and Alzheimer’s. It may also fade as people age. While smell disorders aren’t as apparent as hearing loss or vision impairment, data from the National Institutes of Health (NIH) show that nearly 25 percent of Americans over the age of 40 report some kind of change in their sense of smell, and over 13 million people have a measurable disorder like anosmia, the total loss of smell, or hyposmia, a partial loss. Such conditions can last for years or even be permanent.

It’s not clear if COVID-19 anosmia is different from other instances of smell loss caused by a virus, but those who experience anosmia due to COVID-19 appear to be unique in a few ways. First, they notice the loss of the sense immediately because it’s not accompanied by the congestion or stuffiness that generally characterises the early stages of virally induced anosmia.

“It’s very dramatic,” says Danielle Reed, associate director of the Monell Chemical Senses Centre in Philadelphia, which studies smell and taste loss. “People just cannot smell anything.”

Another notable difference is that many patients with COVID-19 who report losing their sense of smell get it back relatively quickly, in just a few weeks, unlike most people who experience anosmia from other viruses, which can last months or years.

Quagge estimates he’s recovered about 60 percent of his sense of smell so far, but he says in the early days, without any information about when or if he’d ever get it back, he was scared. An avid amateur chef, he had to rely on his family to tell him if the milk was bad, and he couldn’t smell his wife’s perfume. “Stuff that gets to your soul,” he says. “It bummed me out.”

How COVID-19 might affect the ability to smell

Scientists are only just beginning to dig into questions about why COVID-19 causes smell loss, and whether it affects the olfactory system differently than other viral invaders.

“We actually know very little about how smell changes when you get a cold,” says Sandeep Robert Datta, a professor of neurobiology who studies smell at Harvard University. “What are the odds that you have smell loss? How long does it last? That basic thing, we don’t actually know.”

The nose is one of the primary places where SARS-CoV-2, the virus that causes COVID-19, enters the body. Researchers have already identified two types of nasal cells—goblet and ciliated cells—that are likely entry points for the virus. “It does seem like the sino-nasal tissue is the hoppin’ place for this virus,” Reed says. “There’s a lot of people that think that once it’s in the nose, then it’s spilling into the lungs.”

To understand how COVID-19 disrupts the olfactory system, scientists first narrowed down the list of potentially infectable targets. SARS-CoV-2 needs two proteins, ACE2 and TMPRSS2, to enter a cell. So Datta and other researchers searched for vulnerable cells in the olfactory system that expressed these two proteins.

They discovered that olfactory neurons, where molecules bind and trigger a signalling mechanism to the brain, aren’t susceptible to COVID-19. Instead, in a paper published in Science Advances, Datta and his co-authors show that the proteins appear in the olfactory system’s support cells, such as stem cells that regenerate neurons after they’ve been damaged, and in what are known as sustentacular cells, which help physically support neurons, clear out dead cells, and move odorants through the mucus in the system.

Understanding which pieces of the olfactory system are affected is a big first step toward figuring out how the virus disrupts our ability to sense scents. But John Ngai, a neuroscientist at the University of California, Berkeley, and co-author on the paper, cautions that knowing which cells are targeted is just one piece of a much larger puzzle.

Olfactory neurons work by moving charged ions across their membranes. If COVID-19 changes the concentration of ions surrounding these cells, perhaps that is making it impossible for the neurons to send signals to the brain. An immune response could also somehow disrupt the system, or inflammation could be affecting the part of the brain that processes smell.

Even with some early leads, many unanswered questions remain. Why do some people recover in a few weeks while others don’t? Will COVID-19 cause permanent smell loss for some people? And is the virus jumping from the olfactory system into the brain?

By developing a more complete understanding of the ways SARS-CoV-2 interacts with the olfactory system, Ngai says, “we can maybe get a better handle on how to treat people.” Right now, there aren’t good options.

Scent therapy

Tracy Villafuerte has been to an allergist and an ear, nose, and throat specialist since she lost her sense of smell in late March. “They pretty much told me straight out: We have nothing to tell you,” she says.

Like Quagge, she was devastated when she realised she couldn’t smell her kids, the home she grew up in, or whether she was burning broccoli on the stove. They both joined AbScent, an online community for people who are struggling with smell loss. Villafuerte has tried using vitamin supplements, but so far she hasn’t noticed any improvement. “We need answers,” she says. “We need some kind of research to tell us: Do we have hope or not?”

One possibility could be smell training, a kind of physical therapy for your nose. Every day, practitioners take a few small, gentle sniffs from bottles of essential oils like eucalyptus, cloves, or lemon. As they sniff, they focus on the scent, even though they may not actually be able to smell it.

Chrissi Kelly, the founder of AbScent, urges people to imagine what those oils smell like, to conjure up that sensation and the emotional connections one might have to eucalyptus or lemon, the memories associated with cloves or rose. “You need to concentrate,” she says. “You need to look for the smell.”

A body of evidence suggests smell training can be effective, but there’s no guarantee it will work for everyone, and no research on whether it works for COVID-19 smell loss. “There’s no harm in it,” Munger says. “But I think the jury’s still out the extent to which it’s actually going to be therapeutically useful.”

If nothing else, AbScent helps COVID-19 patients with anosmia feel less alone. Trying to describe a scentless existence is difficult, and the condition is often taken less seriously than other sensory losses.

“I’m not looking for sympathy,” Quagge says. “Just don’t joke about it. Until you lose something you don’t understand what you’ve lost. Would I rather lose my sense of smell and taste or my sight or hearing? I don’t know now.”

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