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Sniffing Out an Unusually Common Phenomenon in COVID-19 Patients


Of all the COVID-19 symptoms Benjamin Abella, MD, MPhil, sees in the emergency room, the loss of smell or taste is the strangest — but not because it’s caused by the virus. Other viruses are known to have the same effect. Rather, it’s because so many patients experience it and in different ways.

“We treat people afflicted by flu, cold viruses, by all sorts of viruses in the ER. And most of them do not do this,” said Abella, a professor of Emergency Medicine at the Perelman School of Medicine. “I think it’s one more example of how this virus really forces us to reexamine what we know about viruses and how they operate.”

Over the last two months, anecdotal evidence, case reports, and patient testimonials have documented the smell and taste dysfunction, prompting the Centers for Disease Control and Prevention to recently add it to its official list of COVID-19 symptoms, along with five other new ones.

The emergency department staff at Penn has increasingly started to ask patients about it when they’re under their care. Though it appears commonly among patients, Abella has observed that the degree of loss and the length of time it persists varies.. Many notice it early on before other symptoms manifest. Some experience the loss more intensely. For others, their senses don’t fully bounce back until after they’ve recovered.

“We find it very challenging that this virus has such a range. Some people have no symptoms, while some die within in a day or two,” Abella said. “This loss of smell and taste is another way it disobeys the rules of the viruses we do know.”

The search for answers continues.

Learning about COVID-19 and its symptoms remains a top priority for scientists. More knowledge will lead to better detection methods and treatments, and eventually an effective vaccine. What’s more, these studies will inform researchers and officials on how to fight the next coronavirus or pandemic sure to hit the world again.

Richard L. Doty, PhD, director of the University of Pennsylvania Smell and Taste Center, has been studying the loss of taste and smell and its relationship to disease, including viruses, for more than 45 years at Penn. So when reports of olfactory dysfunction started popping up in the scientific literature and press in February and March, he and a colleague from Iran, Shima T. Moein, MD, PhD, partnered up to dig deeper.

There were reports of smell loss but no published studies, to their knowledge, that applied official smell tests to quantify that loss. Many also noted total smell or taste loss in patients, but Doty believed it had to be more nuanced than all-or-nothing.

Clinicians administered a 40-smell, Persian version of the University of Pennsylvania Smell Test that Moein had devised to 60 hospitalized COVID-19 patients in Tehran toward the end of their stay. Patients were required to identify each of the 40 odors from four alternatives listed for each odor — for example, for pizza, the four choices included gasoline, pizza, peanuts, and lilac.

The number of correct responses provided a test score such that patients could be categorized into one of four categories: mild, moderate, severe, or total loss.

The findings, published in the International Forum of Allergy and Rhinology, showed that the loss of smell affected a majority of patients (59 out of 60) and there was a spectrum. Twenty-five percent had a total loss, known as anosmia, while 33 percent had severe loss. The rest were classified as moderate or mild.

“We show that indeed a significant number of people had a total or near total loss,” Doty said. “But we also found that when the patients were characterized in terms of the degree of severity, using a scale that was developed at Harvard University, that there was no relationship to the degree of smell loss and the severity of the COVID-19 symptoms.”

Researchers don’t know for sure what’s behind the smell dysfunction or why the virus causes more damage in some patients than others. However, it isn’t likely driven by other symptoms, like inflammation or congestion, Doty said. For one, COVID-19 patients without those symptoms experience loss of smell and two, people who recover from those symptoms still experience the loss. The virus likely damages the olfactory and neural membranes, he said, or initiates an immune response that leads lasting dysfunction.

As Doty suspected, there was more to the story than what had been reported.

The researchers also found that more than 35 percent of the patients had no idea they had loss of smell until they were formally tested, suggesting the reported numbers out there for smell loss could be much higher. Smokers, oddly enough, were less likely to experience smell loss.

Another important point, Doty said, is realizing the difference between losses of smell and taste, which people often confuse. Taste buds can only distinguish sweet, sugar, salty, bitter, and umami, a savory or meaty flavor. The rest are all linked to smell. If people hold their nose, for example, and drink coffee, they won’t taste the coffee.

“That’s because when you chew or swallow, the food molecules go back into the nasal cavity and up to the olfactory system from the rear of the mouth. That is the reason for the flavor,” Doty said. “In reality, it’s most likely little or no taste dysfunction is evident, and the perceived loss of flavor is due to smell dysfunction.”

Still, researchers want to confirm that. New studies at Penn, led by Natasha Mirza, MD, a professor of Otorhinolaryngology: Head and Neck Surgery, in collaboration with Doty, will explore the taste component, as well as smell to better understand what’s happening across a more diverse patient population. The patients in the Iranian study were all hospitalized. The tests in the new Penn studies are being distributed to hundreds of health care workers with COVID-19 who can self-administer them. 

Another Penn study by Jay A. Gottfried, MD, PhD, a professor of Neurology in the Perelman School of Medicine and of Psychology in the School of Arts and Sciences, is determining whether measured olfactory dysfunction may be useful in identifying patients in most need of immediate medical attention.

Doty, along with Elizabeth Sell, a Perelman School of Medicine medical student, are also members of the Global Consortium on Chemosensory Research, a group the brings together chemosensory scientists from around the world in an effort to better understand these symptoms. The consortium developed a survey for COVID-19 patients to study possible relationships between the virus and other respiratory illnesses and smell and taste. So far, it has been deployed in 42 countries and in 24 languages, with more than 20,000 responses received and counting. Findings are expected soon.

The disease’s olfactory symptoms may also serve as a potential biomarker to test for COVID-19, Doty said.

As testing shortages and issues affect areas around the nation and world, the findings suggest an opportunity to add smell tests to the existing tool box to help identify patients earlier, particularly those who don’t have any other symptoms. He’s currently exploring that possibility with the U.S. Food and Drug Administration.

During these times, if a person does experience a new loss of taste or smell, Doty and Abella recommend taking it seriously.

“Sudden loss of taste or smell warrants consideration that it is COVID-19 and may be useful information, because it may be time to isolate from other family members or people,” Abella said. “Because the loss of smell and taste is fairly unusual, and we’re in a pandemic, it needs to be further addressed with a physician.”


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