Dr. Nancy Rawson is a scientist at the Monell Chemical Senses Center in Philadelphia and serves on the Science and Medical Advisory Council for The Smell and Taste Association of North America (STANA). She discusses the long-term COVID side effect of loss of taste and/or smell, and how scientists are working to help.
This interview has been edited for length and clarity.
KCRW: What is the difference between anosmia and parosmia?
Nancy Rawson: Anosmia is the term we use to describe a complete loss of smell. You have absolutely no ability to detect any odor whatsoever. It doesn't refer to taste – taste is sweet, salty, sour, bitter, savory. So you can still detect those kinds of sensations. But you can't smell roses, lemons, coffee, or chocolate, things like that.
Parosmia is a related condition. What happens in parosmia is you start to experience odors. But what you're smelling and what you're experiencing is not the way you remember it. So you might go to smell your coffee, and instead, it might smell like garbage, or something completely unrelated. Or, your morning shampoo that always was a very pleasant smell, might now smell just very unpleasant. Occasionally, an unpleasant smell – something that you didn't like before, might now smell not so unpleasant. We hear that as well.
Parosmia is an incorrect aroma experience. And it actually happens quite commonly in people that are recovering their sense of smell following having lost it completely from COVID.
Is it because what you're actually smelling is one isolated component of an aromatic profile?
Right. The research is still ongoing, but what appears to be happening is that the olfactory system, as it's recovering, doesn't recover equally across all of the nerve pathways that detect thousands of different chemicals. So some nerves may be regenerating sooner than others. In order to get the full impact of a coffee aroma for example, you need to be able to detect many different chemicals in a particular proportion in the way that the brain interprets that as coffee. But if you're only now able to detect a few of those, maybe one or two of them, when you smell them by themselves, they don't smell anything like what you think the coffee should smell like.
We do a demonstration with lavender as an example of this. We can take five or six of the critical components of a lavender aroma. And if you smell them individually, none of these chemicals smell anything like lavender. But when you combine them in the right proportion, then you recognize it as lavender. So we really need to have the whole system in order for it to work the way we expect it to work.
How is taste linked to smell?
There is a what's called a retronasal pathway. So when we're chewing, we're releasing chemicals from the food that go up into the air and they go into the nose through what's called the retronasal pathway – through the back of your nose, up into the olfactory cleft. And these aromas that you're experiencing through this retronasal pathway actually impact special sets of receptors that are sent to a part of the brain that integrates flavor information, both smell and taste, and chemical irritation, or texture – all of the other characteristics of food into a flavor perception.
It's this retronasal pathway that makes all the nuances of flavor – beyond sweet, salty, sour, bitter and savory. Without that component of flavor, we really lose the identity of the food. You can't really tell a lemon from a lime without your sense of smell. And it's hard to tell chocolate from coffee without your sense of smell.
Do we know yet what proportion of people with COVID are experiencing long term loss of smell?
The numbers vary, but 10-15% is the general number that seems to be coming out of most of the studies for people that continue to have loss of smell up to two years or more after their initial experience. We are still studying, but probably another 20-30% of those who recovered their sense of smell probably haven't recovered to the point where they were prior to COVID. Certainly have recovered the ability to smell, but they might not be as sensitive as they were before COVID.
The sense of smell is a sense that helps us avoid danger, and gives us clues as to what's safe to eat, what's not safe to eat, for example. It's very disturbing.
It’s very disturbing. It's really unfortunate because as these individuals age, there's a natural diminishment of our sense of smell with age, that is going to be superimposed on this earlier insult that our sense of smell took. So they're starting from a lower baseline. And I'm afraid that we're going to be seeing a lot more people with really impaired sensitivity as we go forward.
You’ve talked about looking at the nasal tissue involved with binding smell receptors at a cellular level for communication to the brain. You said that the virus-infected tissue looked like Swiss cheese – that it was all filled with holes. Does that continue to be the main culprit that you're seeing? Or have you found other culprits that create the losses?
One of the interesting things that came out in the in the past year, was the very unexpected discovery that in addition to the structural integrity of the tissue being affected, the effect of the virus on the supporting cells somehow causes the olfactory nerve cells, and nerve cells that detect odors, to stop making the odor-receptor proteins. So they're not producing the proteins that they need to produce to detect odors. That helps us to understand why people were losing their sense of smell so suddenly.
Do we know how to bring those proteins back?
A lot of the research also in the last year has focused on understanding how to either recover the function of those cells, or regenerate and replace those cells with newly-generated cells that function properly. The exciting news is that there's several clinical trials going on right now that are looking at different ways of promoting recovery of this tissue. The trials are based on work that had been done over many years to understand the types of cells that serve as stem cells for those cells, and the different types of chemical’s growth factors that trigger the generation of new smell neurons. Some of the early animal studies have been quite promising. So I'm optimistic that we'll see some positive outcomes in the future.
Are we talking about an intervention like a surgical intervention of stem cells, or an injection of something?
We're talking about more pharmacological or surgical types of interventions, whether it is stem cells or application, either via injection or via topical application of pharmacological agents that promote regeneration of the tissue.
When I think about the sense of smell, I also think about memory. Has any research been done about how smell loss affects memory?
Smell is intimately connected with memory and the neural connections are very close. We do know that a loss of smell is one of the earliest symptoms of Alzheimer's disease. Changes in the brain related to memory. Impairment also occurs in the olfactory pathway and occurs earlier than in other parts of the brain. However, whether it goes the other direction is an interesting, important question.
I think that the more kinds of sensory information you have to associate with particular events, activities, or people, the better your brain is able to remember it. So for instance, if you are meeting someone, and they're wearing a particular perfume, and they're wearing bright clothing, and they have a very distinctive haircut, you're more likely to remember that person's name. So this is just one component of the overall sensory picture that we make. I think that smell is something that does help us to craft these memories, and to embed these memories in a more long-term way, so that we can bring them back more easily.