An early warning sign of a possible COVID-19 infection is losing one’s sense of smell.

But why is that? What does it mean? And do people regain their sense of smell when they recover?

One of the researchers studying these questions is Richard Doty, professor and director of the University of Pennsylvania Smell and Taste Center at the Perelman School of Medicine.

One of the signature achievements of the center, founded in 1980, is the development of the University of Pennsylvania Smell Identification Test, or UPSIT. It’s a self-administered test of olfactory function that incorporates 40 “scratch and sniff” odorants. It can detect a diminished sense of smell even in people who have not noticed it.

We talked to Doty recently about what researchers are learning about COVID-19 and our olfactory system.

What are COVID-19 patients experiencing as far as taste and smell?

There are more than 600 studies and reports on this topic. The surveys are very inaccurate. Findings range from 5% to 70% of people who claim smell loss. But people are not accurate in noticing or remembering the degree to which they have smell loss. Anywhere from a quarter to a third of people will not be aware they have loss of smell until they are tested.

It turns out that if you measure objectively — with tests such as the one we developed — the results are more consistent. In a study we did of 100 COVID patients, 96% had demonstrable smell loss. They were tested within two weeks of the onset of the symptoms of COVID. Yet nearly a third were unaware of their loss of smell until they were tested.

I should note that most of these patients did not have total loss of smell function, but the majority had severe loss.

We have not found a strong relationship between the severity of other COVID symptoms and smell loss.

What have you learned about how and why COVID-19 may be causing these effects?

Because of SARS and COVID, we’re learning more about how viruses damage the olfactory region.

The virus damages cells in the nose that are critical for maintaining the integrity of the olfactory tissue. There are different types of cells, including receptor cells, that are critical for the system to function. Some of these cells have receptors that, in effect, take up the virus, thereby disrupting their function. For example, cells within the tissue that support the receptor cells have such receptors. Interestingly, research suggests that the main cells that send information to the brain don’t seem to be impacted directly by the virus.

But the cells around them — such as cells important for regeneration — are the ones that seem to be most affected.

We think this is not much different from the effects of the common cold. It’s known that one of the causes of long-lasting smell loss is the common cold. Some people in their 50s who get the common cold notice afterward they can’t smell anymore. Why 50? Their immune systems are not as good. But also, there is cumulative damage as we go through life. After a cold, after exposure to pollution, little islands of damage occur within the olfactory region. But until 70% to 80% of the cells are damaged — we don’t know the exact number — you don’t notice the deficit.

Do people regain their sense of taste and smell? If so, how long, generally, does it take? Do they just have to wait, or is there any kind of smell rehab?

In one study we did, we found that two-thirds of the people who had reduced sense of smell because of COVID regained normal function after about six to eight weeks. Some people will regain it in a week or two. Others will take longer. The presumption is that the cells are regenerating.

But there’s still a significant number of people who continue to have some degree of loss. Interestingly, it may be related to other comorbidities. In one study we published, we found that people who had diabetes were more likely to have a continued loss of their sense of smell.

There also are people with what seems to be permanent loss. I have patients who contracted COVID nine months ago and still can’t smell. That’s analogous to what we see with some persons with influenza, the common cold, and other viral insults.

As far as rehab, there’s a lot of misinformation, unfortunately. The current vogue is to try to smell different odors periodically. The evidence for that is pretty weak. Others tout the benefits of Vitamin C, Vitamin D and alpha lipoic acid, an over-the-counter supplement. But the scientific evidence for this is also very weak.

If there is inflammation, nasal sprays that have steroids may be helpful, but the jury is out on that, as well. But we do know from MRI studies that, early on, there is often inflammation at the top of the nose, but it dissipates rapidly. One notion is that if you can quell that inflammation, you might be able to help minimize the smell loss. That’s still not well-established.

The olfactory system is very complicated. In fact, it’s arguably the most complicated sensory system in our bodies.

One thing we still don’t know is to what degree the virus enters the brain through the olfactory system. We know that many viruses can penetrate into the brain from the olfactory nerves. This whole phenomenon of symptoms remaining long after the virus has passed could, in some cases, be related to blood vessels of the brain becoming inflamed. Some of it could be due to neurological damage. There is not enough information yet to know why there are long-term effects in some people. But, certainly, some of it could be due to penetration of the virus directly into the brain through olfactory pathways.

» READ MORE: Most hospitalized COVID-19 patients develop neurological symptoms, Pitt-led global study finds

Tell us about the new smell tests to detect COVID-19.

There are about 30 out there. At Penn, we’re developing a test based upon subsets of the 40 odorants in UPSIT, our smell identification test. The idea is that these subsets can be used over time to spot when you might start to have a problem, which means you may be getting infected with the COVID virus. Since loss of smell is so common early in the disease, these smell tests might be useful for detecting people who need to isolate themselves, particularly in countries where other testing is not readily available.

I think the interest in this has waned, now that we have vaccines. But it could be theoretically useful in other situations. The down side is that you can have smell loss for a variety of reasons. But, aside from head trauma, sudden smell loss usually implies a virus of some sort. Interestingly, the sensitivity and specificity of smell testing is equal to or better than that of PCR testing, the standard test for COVID.

My own bias is that everyone should get smell-tested. We have hearing tests and vision tests. In the medical world, testing the senses of taste and smell are just as important.

What else have you learned about taste and smell from COVID-19?

What we’re discovering with COVID and how it damages the olfactory system may apply to a variety of viruses. When you think about why viruses would attack the olfactory system, remember that viruses are there to repropagate themselves. Going through the skin or blood vessels to get to the nervous system is difficult. But the olfactory system is right there. It is exposed directly to the environment. The virus only has to get up into the nose to affect the nerve cells.

In some ways, the system is designed to self-destruct to protect the brain. The virus has to use the olfactory cells to get to the brain. But if that cell dies off when it is attacked, the virus doesn’t have a chance to reach the brain. Then a new cell can come along and replace it.

Another thing this pandemic has brought to the fore is how important our sense of smell is for everyday life. Until you lose it, people don’t realize how important it is for food flavor, for safety, for quality of life, for enjoying all the things that make life fulfilling.