Link Between Post Covid Syndrome and Loss of Sense of Smell

More than fifty percent of healthcare workers infected with SARS-CoV-2 (coronavirus) report that their sense of smell has not returned to normal an average of five months post-infection, new research indicates. The findings show that olfactory problems are frequent not only during the acute COVID phase but also "in the long run" and that these problems should be "taken into consideration" when following up with these patients, study investigator Johannes Frasnelli, MD, professor, Department of Anatomy, the University of Quebec at Trois-Rivieres, Quebec, Canada, told Medscape Medical News. Loss of sense of smell could affect the quality of life because it affects eating and drinking, and might even be dangerous, said Frasnelli. "If your sense of smell is impaired or damaged, you might unintentionally eat spoiled food, or you might not smell smoke or gas in your home," he said. In addition, Frasnelli noted that an impaired sense of smell is related to higher rates of depression. The findings will be presented or shown at the American Academy of Neurology (AAN) 2021 Annual Meeting in April.

"Striking" Finding

Research indicates that about sixty percent of patients with COVID lose their sense of smell to some degree during the acute phase of the disease. "But we wanted to go further and look at the long-term effects of loss of smell and taste," said Frasnelli.

The evaluation included 813 healthcare workers in the province of Quebec. For all the patients, SARS-CoV-2 (coronavirus) infection was verified through testing with a nasopharyngeal viral swab.

Participants completed a 64-item online questionnaire that asked about 3 senses: olfactory; gustatory, which includes tastes for example sweet, sour, bitter, salty, savory, and umami; and trigeminal, which includes sensations for example spiciness of hot peppers and "coolness" of mint.

They were requested to rate these on a scale of 0 (no perception) to 10 (very strong perception) before the infection, during the infection, and currently. They were also requested about other symptoms, including fatigue. Most respondents had been infected in the first wave of the virus in March and April 2020 and responded to the questionnaire an average of five months later.

The vast majority of respondents (84.1%) were women, which Frasnelli said was not astonishing because women predominate in the healthcare field.

The evaluation showed that average smell ratings were 8.98 before infection, 2.85 during the acute phase, and 7.41 when respondents answered the questionnaire. The sense of taste was less affected or damaged and recovered faster than the sense of smell. Results for taste were 9.20 before infection, 3.59 amidst the acute phase, and 8.05 after COVID.

Among 580 respondents who indicated a compromised sense of smell amidst the acute phase, the average smell rating when answering the questionnaire was 6.89, compared to 9.03 before the infection. More than half (51.2%) expressed not regaining full olfactory function.

The fact that the sense of smell had not restored to normal for half the participants so long after being infected is "novel and quite striking," said Frasnelli.

Although he noted, this does not necessarily mean all those with a compromised sense of smell "have huge problems." In some cases, he said, the problem "is more subtle or delicate."

Not a CNS Problem?

Respondents also finished a chemosensory dysfunction home test (CD-HT). They were requested to prepare common household food items, for example, peanut butter, sugar, salt, and vinegar, in a particular way, for example, to add sugar or salt to the water and offer feedback on how these smell and taste. For this chemosensory dysfunction home test (CD-HT) analysis, 18.4% of respondents reported having continuous loss of smell. This, Frasnelli said, adds to evidence from self-reported responses and indicates that in some cases, the problem is more than senses not returning to normal. "From the questionnaires, approximately fifty percent said that their sense of smell is still not back to normal, and when we look at the chemosensory dysfunction home test (CD-HT), we see that almost twenty percent of subjects indeed have pretty strong impairment of their sense of smell," he said.

The results showed no sex differences, however, Frasnelli noted that most of the sample were women. "It is tricky to look at the data with regard to sex because it is a bit skewed," he said. Male respondents were older than the female participants, but there was no difference in impairment between age groups. Frasnelli said this was "quite interesting," inasmuch as older people generally lose some sense of smell. The researchers have not yet checked whether the results differ by type of healthcare worker.

They have also not checked in detail whether infection seriousness affects the risk for extended olfactory impairment. However, some research indicates that the problem with the smell is more common in less serious cases, Frasnelli found this could be because the loss of smell is not a huge problem for patients fighting grave health problems. As for other symptoms, many respondents stated lingering fatigue; some stated debilitating fatigue said Frasnelli. However, he cautioned that this is hard to interpret because the participants were healthcare workers, many of whom returned to work during the pandemic and perhaps had not fully rested. He also found that he and his colleagues have not "made the link" between impaired smell and the degree of fatigue.

The coronavirus seems to attack supporting sustentacular cells in the olfactory epithelium, not nerve cells. "At this moment, it appears or seems that the smell problem is not a central nervous system problem but a peripheral problem," said Frasnelli. "But we do not know for sure; it might be that the virus somehow gets into the brain and some symptoms are caused by the effects of the infection on the brain." The researchers will extend their research with another questionnaire to evaluate senses ten to twelve months after COVID. Limitations of the study include the subjective nature of the smell and taste ratings and the single time point at which data was collected.

Confirmatory Findings

Talking about the research Thomas Hummel, MD, professor, Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Dresden, Germany, said the new results regarding the loss of smell after COVID are "very congruent" with what he and his colleagues have found. Research indicates that up to one in five of those infected with SARS-CoV-2 experience olfactory loss. "While the numbers might vary a bit from study to study or lab to lab, I think five to twenty percent of post-COVID patients exhibit long-term olfactory loss," Hummel said.

His group has found that "many more are not back to normal," which agrees with what Frasnelli's study reveals, said Hummel. Kenneth L. Tyler, MD, professor of neurology, University of Colorado School of Medicine, Denver, Colorado, and a fellow of the American Academy of Neurology, said the study was comparatively large and the results "interesting." However, it "offers more evidence there is a subset of patients with symptoms even well past the acute phase" of COVID, the results are "mostly confirmatory" and include "nothing super surprising," said Tyler.

Although, the investigators did attempt to make the study "a little more quantitative" and "to confirm the self-reporting with their validated chemosensory dysfunction home test (CD-HT)," he said. Tyler wondered how representative the sample was and whether the study drew more participants with impaired or damaged senses. "If I had a loss of smell or taste, maybe I would be more likely to react to such a survey," he said. He also noted the complexity of separating loss of smell from loss of taste. "If you lose your sense of smell, things do not taste right, so it could be confounding as to how to separate out those two," he noted.

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