Credit…Stephanie Gonot for The New York Times

FEATURE

What Can Covid-19 Teach Us About the Mysteries of Smell?

The virus’s strangest symptom has opened new doors to understanding our most neglected sense.

Credit…Stephanie Gonot for The New York Times

By Brooke Jarvis

Danielle Reed stopped counting after the 156th email arrived in a single afternoon. It was late March, and her laboratory at the Monell Chemical Senses Center in Philadelphia had abruptly gone into Covid-19 lockdown. For weeks, there had been little to do. Reed, who is famous in her field for helping to discover a new family of receptors that perceive bitter flavors, had spent years studying the way human genetics affect the way we experience smell and taste. It was important but niche science that seemingly had little to do with a dangerous respiratory virus spreading around the globe.

And then one Saturday, she checked her email. Reed watched in amazement as the messages proliferated. It wasn’t how many threads there were, though that was overwhelming, but the way they seemed to grow like Hydras, sprouting in all directions. Recipients copied other people they thought might be interested in the discussion, who added more people, who added still others, across a huge range of countries and disciplines. The cascading emails were all responding to the same rather obscure news alert, meant for ear, nose and throat doctors based in Britain. It was titled: “Loss of smell as marker of Covid-19 infection.”

The week before, Claire Hopkins, the president of the British Rhinological Society and an author of the alert, was seeing patients in her clinic in London when she noticed something odd. Hopkins, who specializes in nose and sinus diseases, especially nasal polyps, was accustomed to seeing the occasional patient — usually about one per month — whose sense of smell disappeared after a viral infection. Most of the time, such losses were fairly self-explanatory: A stuffy, inflamed nose keeps odorants from reaching the smell receptors at the top of the airway. Sometimes these receptors are also damaged by inflammation and need time to recover. But patients were now arriving with no blockage or swelling, no trouble breathing, no notable symptoms, other than the sudden and mysterious disappearance of their ability to smell. And there were nine of them.

At first, it didn’t occur to Hopkins to think about the recently declared pandemic that was dominating the news. None of the patients had traveled to Italy or China, so they didn’t meet the government’s criteria for testing or quarantine: The virus, she understood, was not yet spreading in Britain.

As each new patient told a strange yet similar story, she began to wonder. A colleague in Italy, where the virus was known to be spreading, had mentioned that frontline doctors were losing their senses of smell and taste. Hopkins assumed that a mild version of Covid-19 was causing a standard post-viral loss of smell. But shortly after seeing the nine patients, she attended an online chat for physicians hosted by the American Rhinologic Society. A French doctor posted that he had recently seen an increase in cases of sudden smell loss without any blockage. Had anyone else noticed something similar? Yes, several doctors from the U.S. replied. They had started to hear rumors from colleagues in Iran and Italy of odd spikes in patients who had unaccountably lost their sense of smell.

Hopkins decided to keep digging. She found that in China, an unusual number of ear, nose and throat specialists — doctors who would have been sought out by patients troubled by an unexplained loss of smell — had contracted the virus. A report in South Korea found that of 2,000 people with mild cases of Covid-19, 30 percent lost their sense of smell. The same week that patients were streaming through Hopkins’s office, there was an article in a German newspaper about a virologist named Hendrik Streeck who went door to door interviewing some of the country’s earliest patients. He found smell loss in two-thirds.

None of these anecdotes amounted to the sort of rigorous proof that Hopkins, with her research background, was used to seeking. She also doubted that her theory would attract much public interest, even in the face of a world-changing pandemic. A career studying smell had taught her that most people simply don’t consider the sense to be particularly interesting or important. It was always hard to get financing to study smell or smell disorders, and patients who lost their olfaction often told her that their friends and family shrugged the condition away: It was only smell, after all.

Still, Hopkins and Nirmal Kumar, the president of ENT UK, decided to put out an alert, hoping it would at least encourage their fellow nose doctors to take extra precautions. Then, that same weekend, Rudy Gobert — the Utah Jazz star whose Covid-19 diagnosis caused the N.B.A. to abruptly suspend its season (just after Gobert mocked the danger by touching all the microphones at a news conference) — announced that he had lost his sense of smell. Hopkins’s alert ricocheted around the world, picked up by news outlets and shared on social media by people desperate for information about the workings of the new virus and any signs that they might already have been exposed. It also kept landing, over and over, in the inboxes of Danielle Reed and hundreds of other scientists who studied smell in some way.

The breadth of their backgrounds was stunning, even to one another. There were neurobiologists and otorhinolaryngologists, virologists and food scientists. There were chemists and data specialists, cognitive scientists and nutritionists, geneticists, psychologists, philosophers — an indication of how complicated the interplay of smell, taste and human life is. Like Hopkins, many of them were used to their work being as underappreciated as the senses they studied.

Smell is a startling superpower. You can walk through someone’s front door and instantly know that she recently made popcorn. Drive down the street and somehow sense that the neighbors are barbecuing. Intuit, just as a side effect of breathing a bit of air, that this sweater has been worn but that one hasn’t, that it’s going to start raining soon, that the grass was trimmed a few hours back. If you weren’t used to it, it would seem like witchcraft.

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Credit…Stephanie Gonot for The New York Times

But of course you are used to it. You may even take it for granted. Perhaps you would rank smell, as most adults in a 2019 survey did, as the least important sense, the one you would be most willing to lose. Perhaps you would even agree with the majority of young people who, in 2011, told McCann Worldgroup, a marketing company, that smell was less valuable to them than their technological devices. As PC Magazine trumpeted, with a mixture of scorn and glee: MAJORITY OF KIDS WOULD RATHER LOSE THEIR SENSE OF SMELL THAN LOSE FACEBOOK.

The writers of that headline seemed to see disregard for smell as shocking, a marker of a technology-obsessed and perhaps uniquely shallow generation. That reaction would have come as a surprise to Immanuel Kant, who wrote, in 1798, that smell is both the “most ungrateful” and the “most dispensable” of the senses. Charles Darwin considered smell to be “of extremely slight service” to humans. Until quite recently, one smell researcher told me, most general medical textbooks didn’t bother to include a chapter on smell or taste, apparently considering them insignificant afterthoughts to the functioning of the human body. From Plato and Aristotle (Plato considered smells “half-formed,” and Aristotle wrote that “man smells poorly”) to Descartes and Hegel (one called vision the “noblest of the senses,” while the other dismissed smell and taste as too pedestrian and vulgar to be included among the senses in his aesthetics), we have spent centuries writing off our own sense of smell.

One reason we have discounted smelling is our belief that we’re bad at it. Smell was the province of lesser animals, we told ourselves, of pigs rooting out truffles and sharks scenting blood, while humans were creatures of reason and intellect who managed to stand up and grow huge brains and leave that life far behind — and, literally, below — us. Scientists followed Paul Broca, a 19th-century neuroscientist, in pointing to the relative smallness of our olfactory bulbs as evidence that our brains had triumphed over them, and likewise over the need to pay much attention to smell at all. In the late 1950s, a pioneering ear, nose and throat specialist, Victor Negus, summed up the consensus view in a book about the comparative anatomy of the nose. “The human mind is an inadequate agent with which to study olfaction,” the specialist wrote, “for the reason that in Man the sense of smell is relatively feeble and not of great significance.” For centuries, when scientists studied smell at all, they tended to focus on isolating particular odorants (they thought they could find the odor version of primary colors) and creating elaborate organizational systems that shuffled them into various categories (“History is littered with the wrecks of Universal Classifications of Smell,” the smell scientist Avery Gilbert wrote in his book “What the Nose Knows.”) Questions of how humans smell and how our smelling, in turn, interacts with our bodies, our health and our behavior were of far less interest. The sense, after all, was seen as practically vestigial: an often handy, sometimes pleasant but ultimately unimportant holdover from our distant past.

The notion of smell as vestigial has itself come to seem outmoded. That’s because of a renaissance in smell science. While we have long understood the basic mechanisms of vision and audition, it has been less than 30 years since the neural receptors that allow us to perceive and make sense of the smells around us were even identified. The discoverers — Linda Buck and Richard Axel — were awarded the Nobel Prize in 2004.

The revelation opened the door to a new way of understanding the olfactory system, as well as to a new, ever-expanding world of research. A system assumed to be unsophisticated and insignificant turned out to be quite the opposite. Where vision depends on four kinds of receptors — rods and three types of cones — smell uses about 400 receptors, which are together estimated to be able to detect as many as a trillion smells. The complexity of the system is such that we’re still unable to predict how, or even if, a given chemical will be perceived by our olfactory system. The old quest to map odorants and their perception is now understood to be a wildly complicated undertaking. Joel Mainland, a neuroscientist at the Monell Center who is working on the problem, told me that while maps of color vision are easily presented in two dimensions, an eventual olfactory map might require many more.

Recent studies have begun to puncture our conviction that we are too sophisticated to be good at smelling. Our brains know the difference between exercise sweat and fear sweat, and between a glass of wine that has recently contained a fruit fly and one that has not. They seem to compel us to sniff our fingers shortly after we shake other people’s hands, searching for information about them that we’re not consciously aware of processing. One inventive study found that, provided we’re willing to crawl around with our faces in the grass, humans are fully capable of finding a scent trail while blindfolded — not as well as a dog, granted, but we can follow it. Another found that we can tell, just from sniffing a T-shirt another person has worn, whether that person’s immune system is similar to our own. (If it’s different, we find the person more attractive.) But here’s what’s really impressive: Our noses can also distinguish between two groups of mice that have different immune systems.

Several years ago, the Rutgers scientist John McGann took a critical look at Broca’s 150-year-old dismissal of our olfactory bulbs and found it to be mistaken: Our bulbs are shaped a little differently, but when you compare how many neurons they hold with those of other mammals, humans are solidly “in the middle of the pack.” There are, he pointed out, even some odors we can smell better than rodents or canines can.

A much-discussed unit of measurement in smell studies is the J.N.D. — the Just Noticeable Difference, or the degree to which chemicals have to differ from one another in order for us to tell them apart. In November, a new paper in Nature advanced the quest for a map of olfactory perception by creating a model that can predict what odorants will smell like by contrasting their chemical makeup with that of other smells. The work relied on volunteers comparing hundreds of different odors and found them to be almost frustratingly good at it. “The failure to reach an absolute J.N.D. provides for yet additional evidence of an exquisite sense of smell in humans,” the authors said. “To rephrase this result: It is simply very hard to generate two multicomponent odorants that humans cannot discriminate.”

One of the authors, Noam Sobel of the Weizmann Institute of Science in Israel, also worked on the scent-trail study and the one about handshakes, as well as a study that found that an automatic sniff reaction — taking longer breaths when something smells good and shorter ones when something smells bad — is a reliable predictor that someone will eventually wake up from a coma. In the early days of the pandemic, he was spending his days at testing centers in Tel Aviv, trying to figure out whether an artificial nose could sniff out the novel coronavirus — not a crazy notion, because dogs are learning to do it, and because at least one human has proved her ability to identify sufferers of Parkinson’s disease just by smelling them. Sobel and his colleagues also started a website, SmellTracker.org, where people who were worried about Covid could track changes in their ability to smell a variety of common household items.

We think that smell is less important to us than our other senses only because we’re fooling ourselves, Sobel told me. After all, you wouldn’t eat a beautiful cake if it smelled like sewage, but you would probably try some ugly gloop that smelled like cinnamon. Covid, he hypothesized, could kick off a sort of global reckoning, forcing our conscious minds to recognize what our brains have known all along. “People are unaware smell is important until they lose it,” he said. “And then they’re terrified.”

The growing mess of emails that followed Hopkins’s alert in March quickly became so unwieldy that the scientists decided to move to a more formalized group. Within days, it had 500 members, from dozens of countries, and a name: the Global Consortium for Chemosensory Research. (The group eventually stabilized at around 630 members, from 64 countries.) “We decided to become a global organization,” explained Valentina Parma, a psychologist who, along with Reed and seven others, helped found the G.C.C.R.’s leadership committee. “We all got together to try to figure out what’s going on.”

The sheer number of questions was daunting. How many Covid patients experienced smell loss? How fully did smell disappear? (Smell loss is known as anosmia when it’s complete, and hyposmia when it’s partial.) Was Covid-related smell loss truly distinct from that caused by other viruses? How many patients would be able to recover their olfaction, and how long might it take?SMARTER LIVING: The best advice from The Times on living a better, smarter, more fulfilling life.Sign Up

Many patients were reporting loss of taste as well as smell, but this, too, was complicated. Thanks to a process called oral referral, which causes us to perceive what’s happening in the nose as if it’s inside the mouth, smell is integral to our experience of taste. People often struggle to separate the two, certain that they have lost their sense of taste when the taste buds — which detect only sweet, salty, bitter, sour and umami flavors — remain fully functional. There was also the question of the sensations we experience through neither olfaction nor taste, but via the nerves of our trigeminal system: the coolness of mint, the spice of peppers, the bubble of carbonation. Were these also affected? (The three, together, are known as our chemosensory senses: those we use to detect the presence of chemicals in our environment.) Answering these questions could help solve the most urgent puzzle: What exactly was happening inside patients to make their sense of smell disappear in such an unusual way? Could Covid-related smell loss teach us anything new about how the virus worked? Or about how we did?

As a panicked world closed down around them, members of the G.C.C.R. started meeting online every day, working on a plan to survey people with respiratory illnesses about their symptoms. There were so many eager researchers, from so many countries, that the survey was quickly translated into more than 30 languages. Though the group considered using several of the more objective olfaction tests developed in recent decades, they decided, given the urgency of the situation, to use the simplest method: asking patients to assess their own perceptions. The survey included, along with rating scales for smell and taste and multiple-choice options about diagnoses and symptoms, a series of open-ended text boxes where people could write as much as they wanted about what they could and couldn’t smell.

It turned out that they wanted to write a lot. Many people went on for pages and pages, offering enormous detail and torrents of feeling. “This was freaking people out,” says Pamela Dalton, an experimental psychologist at the Monell Center who studies the interaction between cognition, emotion and the way we perceive odors, and who also worked on the survey analysis. They wrote things like “I’m inhaling, and there’s nothing there.” People frequently described themselves as feeling adrift — disconnected from a world that felt wrong, uncanny, confusing. Reed noticed that many respondents, ejected from the system because they reported symptoms that weren’t recent enough to be included in the design of the study, signed back in with falsified dates so they could still participate. Those answers wouldn’t be included in the analysis, but Reed understood why they mattered. “Ultimately, people just want to tell their story,” she said.

In a matter of weeks, 40,000 people took the survey, and the members of the G.C.C.R. began to search for patterns in the data. They quickly established that people who lost smell and tested positive for the coronavirus weren’t encountering the typical nasal blockage — they often referred to the loss as “sudden” and “creepy” — and that they were also noticing genuine impairments not just to their olfaction but in many cases to their taste and trigeminal sensations as well. This clearly wasn’t the typical pathology of smell loss following a virus.

The scientists also noticed that a disconnect was forming between what the data showed and how the wider world responded. Early on, data from apps for tracking symptoms showed that smell loss was more common than the fever or cough the virus was known for; it also had the diagnostic advantage of pointing directly to Covid, rather than to another respiratory illness. And yet schools and restaurants and airports continued to use forehead thermometers to screen for fevers — a symptom that many people with Covid never experienced. Later G.C.C.R. analysis showed that smell loss was, in fact, the most reliable predictor of Covid, and that this was true even for people assessing their own smell loss (which, research has shown, is something people tend to be quite bad at). Reed and other researchers also found that objective smell tests, in which patients have to prove themselves against actual stimuli, were able to catch many extra Covid cases among people who failed to realize when their sense of smell had changed. “The better we ask questions about smell,” Parma says, “the more people we find.”

In Britain, Hopkins was growing frustrated. The weeks kept passing, and smell loss still didn’t appear on the official list of symptoms recognized by the National Health Service — a list that determined who qualified, or didn’t, for coronavirus testing. One of her patients, a physiotherapist, was told to keep reporting to the I.C.U. where he worked, even though his family was sick and he had lost his sense of smell. He convinced his team that he should be allowed to self-isolate, but Hopkins wondered how many other people were in similar situations, sent out into the world to spread a virus they were assured they didn’t have. “I can still put in my symptoms into NHS 111” — the portal through which patients access care from the National Health Service — “and claim to have muscle ache, fatigue, loss of smell, diarrhea and be told that I don’t have coronavirus,” she told the BBC in mid-May. “I think that is now actually, clinically, negligence.”

Months later, after the N.H.S. officially recognized smell loss as a Covid symptom, I asked Hopkins why she thought that recognition of smell loss as a symptom of Covid had taken so long. In part, she replied, the trauma of the serious cases had obscured, in the data as well as from public notice, a symptom that was primarily noticeable in people with only mild disease. But she also believed that there was another important factor, unrelated to the virus. Covid arrived in a world that had spent far too long not taking smell seriously.

This may be the moment for a belated disclosure: Part of what interests me about the science of smell is that I myself am anosmic. (The outsider to whom smell looks like a superpower? That’s me.) I have no idea if my inability to smell is congenital or if my olfaction stopped working before I had the chance to remember it. I did have a lot of ear infections when I was very young, which are known to damage smell. Infants aren’t routinely screened for smell disorders, as they are for hearing or vision, and it’s common for anosmic people not to realize fully that they’re different until, on average, their early teens. That’s about how old I was when my sister came home to find me blissfully cuddling our skunk-sprayed dog, and the pieces began to fall into place. (Years later, the same sister came home just in time to stop me from lighting a match in a cabin I had accidentally filled with propane.) Before I learned what anosmia was, I assumed, whenever people brought up the things they were smelling, that this was a skill I had yet to figure out, that I just wasn’t doing it right.

One thing you notice when you can’t smell is how much time people who can smell spend talking about it. Friends are always curious about whether I can taste food (I love food, though I care primarily about textures and the flavors the actual taste buds perceive), but that’s the main difference they imagine. They don’t seem to realize all the other ways that smell is constantly on their minds. Smell is no big deal, until it’s missing.

As the pandemic progressed, the G.C.C.R. surveys showed that the experiences of patients who lost their sense of smell were beginning to diverge. There were those — about three-quarters of Covid patients, Reed says — who recovered their olfaction fairly quickly, from a few weeks to a couple of months after losing it. Then there were those who gained it back slowly, over the course of many months. But there was a smaller percentage who, at six months, didn’t seem to be recovering it at all.

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Credit…Stephanie Gonot for The New York Times

This was what Chrissi Kelly, another G.C.C.R. member, feared might happen. In 2012, she lost her own sense of smell after fighting a virus she caught on an airplane. She spent the next two years feeling depressed, forgetful and like a fundamentally different person than she was when she could smell. “Life lacked color‚ luster,” she told me. “My sense of humor had deserted me.” The experience was so destabilizing that she began digging into scientific papers about smell loss — there weren’t many of them, and there was almost nothing for a lay audience — and contacting their authors, searching for possible treatments. She started practicing “smell training,” a little-known technique for recovering some olfaction by regularly smelling strong odors, and she started a support group on Facebook for other people with the condition.

Before Covid, the group, called AbScent, had grown to around 1,500 members, most of whom lost olfaction after a head injury, a virus or a sinus disease. And then the pandemic began. It soon became a nearly full time job just to process the flood of thousands of distressed people who were asking to join AbScent. In the group, people mourned specific smells and flavors, shared their struggles with nausea and weight loss or gain as they navigated an altered relationship with food. They commiserated about the new dangers of life: food poisoning, gas leaks, not noticing that dinner was burning. (This month, a Texas family whose members lost their sense of smell to Covid narrowly escaped a house fire after the only uninfected member, a teenager, smelled smoke and woke everyone else up.)

Many people also struggled with depression, symptoms similar to those of post-traumatic stress disorder and feelings of relentless isolation and disconnection from the world around them. It felt, some people said, as if they were living their lives in black and white, or trapped behind a sheet of glass; their sense of normalcy and well-being had disappeared with their olfaction. “I feel alien from myself,” one person wrote. “Detached from normality. Lonely in my body. It’s so hard to explain.” Another described feeling “discombobulated — like I don’t exist.” Kelly kept the group closed, out of respect for what she described as the “profound depths of sorrow and anger and anxiety” that people shared there.

Kelly sometimes noticed that requests to join the group would suddenly increase from a certain city or region, only to later read about a new spike in cases. She committed herself to responding to each person individually, spending hours every day. “It still feels like an emergency response,” she said over Zoom more than six months after the official start of the pandemic. As the numbers ballooned and the Covid patients began to overwhelm the discussion, Kelly started a separate support group just for them, which quickly dwarfed the original.

And then, quite suddenly, many people in the group began reporting something new. Their sense of smell seemed to be returning, yet it was coming back … broken. Things no longer smelled the way they had, and usually the new smell was bad: Food smelled like gasoline or cigarettes, or scented body wash was like burning rubber. Terrible smells even intruded when nothing odorous was around. A boyfriend no longer smelled or tasted right, and the poster had begun to avoid kissing him but had not told him why. “Poo now smelled better than coffee,” another person noted. Analysis of the G.C.C.R. surveys later found a similar pattern: As the pandemic progressed, the symptoms — known as parosmia, incorrect smells, and phantosmia, phantom smells — went from nearly unknown to incredibly common. Kelly and Hopkins and other researchers collaborated on a paper analyzing the posts in AbScent and found that, on average, three months elapsed between smell loss and the arrival of faulty smells. To manage what she called “the rising tide of parosmia,” Kelly spun off