Q&A: What Taste and Smell Tell Us During COVID-19 and Beyond

Many people are learning for the first time about the loss of taste and smell as a symptom for viruses. You, however, have been researching taste and smell since long before the coronavirus pandemic. Why is this an important area of study, and what drew you to it?

Taste and smell are what we call the chemical senses, and these senses drive critical behaviors for survival— things like seeking food, seeking a mate, and avoiding danger. All living creatures use these chemical senses to respond appropriately to their environments. Long before evolution had created eyes or ears, we could detect chemicals. It’s the most evolutionarily ancient system in terms of sensing our environment, which makes it really fascinating to study.

We’re swimming in a pool of chemicals. They’re all around us, and inside us as well. We have evolved into being particularly sensitive to things that drive our survival, like food: we avoid potentially dangerous, bitter compounds and are attracted to sweet things that have calories that help us to grow and live. But today there is often excess availability of positive stimuli, like sweetness and saltiness, leading us to eat more than we need.

I studied nutrition earlier in my career, and I worked at Campbell Soup Company for a while. At that time everybody was talking about how much salt was in the soup and how we could reduce it—and about how much we could reduce it before people would say that they didn’t like it. It became very clear that something as simple as salt had an important role to play in overall flavor, because when you reduced the salt in something like V8® juice, for instance, or in some kinds of vegetable soups, you started to taste the bitterness of the vegetables. So it was very interesting for me to learn how flavor was created by these different sensory characteristics and why people like things so much that just telling them to “eat less salt” or to “eat less fat” doesn’t work.

Eventually, I went to Monell, and I started my work there by studying smell—olfaction. I looked at individual olfactory neurons and tried to understand how they detected odors. I became a cell biologist of taste and smell in order to get inside the cell to figure out what it was doing.

According to the website of the Monell Chemical Senses Center, loss of taste and smell can be an “early alarm system.” What does that mean?

The olfactory system is part of the brain. The nerve cells that sit in your nose sense the air coming in, and they’re directly connected to the brain, specifically to the olfactory bulbs, so they have axons that project through the cribriform plate to your olfactory bulbs in the brain. From the bulbs, they connect to the hippocampus and the amygdala, which are parts of your brain important for learning, memory, and emotion. So they’re really only two synapses away from the parts of the brain that are affected in many neurodegenerative diseases.

In Alzheimer’s disease, an inability to identify odors is one of the earliest symptoms. There is degeneration in the olfactory bulbs and in the parts of the brain that connect to these bulbs very early in the progression of Alzheimer’s. Diminished sense of smell is like a canary in the coal mine—a signal for neuropathology in other parts of the brain and for neurodegenerative disease.

We have also studied olfactory neurons as a way of better understanding what’s happening in the brains of people with depression, bipolar depression, or schizophrenia. The olfactory neurons are the only part of the brain that you can get at noninvasively, so you can actually do a nasal brushing or a little tiny biopsy to collect some of these cells, study them, and get a snapshot of what’s going on in a nerve cell, in real time, in a living person. So this is a very powerful way of understanding the early stages of some of these disorders, in which neurological effects may show up in the olfactory system first.

Because many viruses and bacteria, including the SARS-CoV-2 virus, get into your olfactory system through your nose, that’s the first place that these pathogens have an ability to cause problems. What’s been interesting with COVID-19 is that SARS-CoV-2 doesn’t directly kill the olfactory neurons. It accesses supporting cells, called sustentacular cells, that help to control the environment that the olfactory neurons exist in—the virus actually takes those cells out. Once those cells are killed, the integrity of the olfactory epithelium is damaged, and the primary olfactory neurons can’t function. Therefore, what we see with COVID-19 is a very sudden drop-off in the ability to smell that occurs quite early in the progression of the disease.

Speaking of COVID-19, Monell has developed a rapid smell test called SCENTinel. How will this unique screening tool fit into the pandemic response, and when will it be available?

We realized quickly that there was a need for a very reliable and easy-to-implement tool for assessing smell function. What we learned through our work as part of the Global Consortium for Chemosensory Research (GCCR) is that people don’t necessarily notice a change in their sense of smell, but it can be detected through testing. If you just ask people if they lost their sense of smell when they had COVID-19, the reported incidence is about 40%. If you test them, you realize that the actual incidence is closer to 70% or more. Many people already have a reduced sense of smell if they’ve had sinus infections or if they’re over 65, so they are less likely to notice a change due to COVID-19. Younger adults tend to be more aware of this symptom. Indeed, as more young people became infected by SARS-CoV-2, they reported that they went from having a normal sense of smell to having no sense of smell, and the GCCR was formed to address this.

There were other smell tests out there, but they were very lengthy, their scratch-and-sniff format caused unwanted variability, and they did not measure intensity of odors. We developed the SCENTinel test as a rapid screening tool that can assess a patient’s abilities to detect an odor, identify it, and measure its intensity—three key components.

To take the test, you lift up the film on each of the three panels, one at a time, sniffing each panel and then covering it up again, so it’s not contaminating the next one that you try to smell. Using your phone, you scan the UPC code to bring up a questionnaire. The first question asks you to indicate which panel has the odor. (The SCENTinel is designed so that there are three panels, but only one has an odor, reducing the likelihood that you’ll get it right by chance.) The second question asks you to rate the intensity on a linear scale, with zero being undetectable and 100 being the strongest imaginable. The final question asks you to identify the odor based on four choices. We’ve used odors that are generally recognizable in the United States such as popcorn, Play-Doh™, and bubble gum. (We would develop culturally selective ones for different places.)

We envision this test being used in a setting where you would possibly take it every day-—before you go to work in a manufacturing plant or at an Amazon warehouse, for example. This would allow you to see your results over time, and if you saw a sudden drop-off in your ability to smell, that would be a signal to go get a COVID-19 test.

As for the status of the rollout: the test is currently being used in several research projects to validate it in different settings, different age groups, and so forth, and we’re working with a small company to commercialize it. We hope that eventually, post-pandemic, this test will become part of every annual health checkup that people get. You might take one at your dentist’s office or at your doctor’s office so that you would have this information as a baseline and over time. As I mentioned earlier, it can provide a signal for other kinds of issues, such as neurological issues that need to be attended to. That’s our ultimate vision for it.

What expert advice would you give to someone who has lost their sense of taste and smell as a result of COVID-19?

The first thing I would do is to send them to patient advocacy websites, such as www.abscent.org, www. fifthsense.org, and www.thestana.org, which is the Smell and Taste Association of North America, a new organization that I’m helping to get started. I would suggest that people go to these sites and look at their resources. They can talk to other people who are going through this, find suggestions for coping mechanisms and cooking ideas, and tap into information about prognosis and the potential for recovery.

There’s also information about a therapy called smell training. We don’t have extensive data yet as to whether this therapy helps people who are recovering from COVID-19-induced smell loss—it’s too soon to say—but there are data for other types of smell loss indicating that smell training can help accelerate recovery, particularly for post-viral smell loss. This therapeutic process is similar to what you might think of doing if you were relearning how to play the piano and hadn’t played in a long time. What would you do? You would sit down and practice scales, retraining your brain to match each note with where it is produced on the piano. For smell training, you sit down with a set of odors each day, sniff them, and then think about what each one is. This kind of activity can help the brain to remember to reconnect those signals with that quality. We think that the therapy helps to reestablish neural connections and to promote regeneration of the olfactory cells.

The other thing that we haven’t talked about yet often happens during the recovery process. People go through a stage called parosmia, when something doesn’t smell like it should—and usually it smells bad. Your coffee might smell like feces, or your beloved pet might smell like burning rubber. This is a very difficult condition for people to manage and cope with. It’s actually probably worse than a reduced sense of smell or having no sense of smell. People experiencing parosmia have trouble eating because food doesn’t taste like food and can smell extremely unpleasant. We suspect that as cells are regenerating, they may not be initially connecting to the right places in the olfactory bulbs, and it could take months for those connections to get refined and sorted properly.

Parosmia is a condition that we hardly ever saw before the emergence of COVID-19. Monell had a clinic where we saw patients from all over for many years, and we rarely had patients come in with this condition. Now, with COVID-19, parosmia is becoming much more common, occurring at some point during the recovery process. For anyone experiencing parosmia, my advice would be, don’t give up: there is the potential for recovery even after many months.

Is there anything else you want AWIS members or the public to know?

I would strongly encourage people, even those who have their sense of smell, to be allies to the people who have lost theirs and those who were born without it. Some of the ways you can be supportive include going to the websites I mentioned before, participating in research, taking surveys, and supporting organizations that are trying to be advocates for patients.

Resources for people experiencing loss of smell and allies:
www.thestana.org
www.abscent.org
www.fifthsense.org.uk

Opportunities to participate in research:
https://gcchemosensr.org/

Monell COVID-19 resources:
https://monell.org/COVID-19-resources/

This interview has been edited for length and clarity.

Dr. Nancy Rawson, an AWIS member since 1993, is Vice President and an Associate Director of the Monell Chemical Senses Center in Philadelphia, a nonprofit research institute dedicated to the study of taste, smell, and related senses (www. monell.org). She holds a master’s degree in nutrition from the University of Massachusetts and worked at Campbell Soup Company prior to obtaining a doctorate in biology from the University of Pennsylvania. From there she joined the Monell Center as a postdoctoral fellow and then as a faculty member, studying the cellular basis for taste and smell. She gained experience in the food/ingredient industry, as Chief Scientific Officer of WellGen, Inc., and then as Director of Basic Research at AFB International, before returning in 2016 to Monell, where she manages its corporate partnership program, leads strategic planning activities, and serves as Secretary of the Board.