Scientists discover key reason why long-COVID patients experience long-term smell loss

Scientists are working on determining the cause behind one of the most distinctive side effects of earlier strains of COVID-19—losing one’s sense of smell.

Although this symptom has become less common as newer variants spread, back in 2020 a sudden loss of smell was an immediate sign to go get tested for COVID-19.

And although this loss of smell has been temporary for many, for others that sense never properly returned, leaving millions struggling with loss of smell for months or even years. In order to find out the mechanisms behind this, a new study looked at olfactory epithelial samples collected from 24 people, including nine people experiencing long-term loss of their sense of smell due to a case of COVID-19.

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"One of the first symptoms that has typically been associated with COVID-19 infection is loss of smell," Bradley Goldstein, associate professor in Duke's Department of Head and Neck Surgery and Communication Sciences and the Department of Neurobiology and senior author of the new research, said in a press release.

"Fortunately, many people who have an altered sense of smell during the acute phase of viral infection will recover smell within the next one to two weeks, but some do not. We need to better understand why this subset of people will go on to have persistent smell loss for months to years after being infected with SARS-CoV2.”

According to a study published earlier this year, as many as five per cent of COVID-19 survivors have long-lasting struggles with loss of smell, coming out to estimated 15 million people. And it’s still happening, even if the rate has gone down—around 17 per cent of people lost their sense of smell due to the Omicron variant when it became dominant in 2021.

• Read more: Long COVID and smell: How to get the treatment you need

In this recent study, researchers found that among those suffering from chronic loss of smell following COVID-19 infection, there was inflammation in the tissue of the nose where the smell nerve cells are located, and that there were also fewer olfactory neurons within the nose overall compared to control groups, which researchers suspect could be due to damage from the inflammation.

In a paper published in the journal Science Translational Medicine in mid-December, researchers describe how they didn’t find any detectable SARS-CoV-2, the virus that causes COVID-19, in the subjects, but ongoing inflammation was persisting nonetheless in those with chronic smell issues.

Researchers obtained additional samples from those who had been suffering from chronic loss of smell for at least four months since contracting COVID-19. None of the patients were acutely ill with COVID-19 at the time of sampling, nor had they previously had medical interventions such as intubation.

One big issue was that in the affected patients who previously had COVID-19, part of the immune system had been thrown off balance—T-cells in the olfactory samples were working overtime, driving the inflammation.

The job of T-cells is to attack specific foreign particles in order to help the body fight a virus, but in these patients, the virus was long gone.

"The findings are striking," Goldstein said. "It's almost resembling a sort of autoimmune-like process in the nose.”

It’s important research into an issue that has left some without the ability to smell anything, a condition called anosmia, and others with a distorted sense of smell that impacts their ability to eat food without nausea. Parosmia is the term for when a person’s sense of smell is thrown off to the point where many things smell rancid or have a chemical cast.

Previous research on the topic has largely focused on autopsies of patients who died after having COVID-19, meaning they weren’t able to ask patients about their experiences of smell or have them take smell tests as researchers did in this new study.

Although this research answers some questions, more needs to be done to truly nail down the reason for long-term loss of smell in COVID-19 patients. The study notes that there are still several possibilities for the cause of the long-term damage, one being that the initial cell damage of the acute illness may have overwhelmed the ability of stem cells within the olfactory area to rebuild the cells responsible for smelling.

A theory seemingly disproved by this new research is that long-term loss of smell was driven by ongoing infection, which researchers found no sign of.

There were signs of hope—researchers observed neurons attempting to repair themselves even after long-term damage.

"We are hopeful that modulating the abnormal immune response or repair processes within the nose of these patients could help to at least partially restore a sense of smell," Goldstein said.

His lab is currently working on studying this aspect of the issue. Researchers acknowledged that their current study is limited by its smaller scope.