Why the sense of smell sometimes fails

After surviving a Covid-19 infection, some people still suffer from a loss of smell months or years later. A study now shows that one reason for this is a persistent inflammatory reaction in the olfactory tissue of the nose. The immune system attacks the olfactory nerve cells so that their number decreases. The new findings could help to develop therapies so that those affected can regain their sense of smell.

A typical symptom of a Covid-19 infection is the disappearance of the sense of smell. The reason for this is probably that the Sars-CoV-2 coronavirus attacks the so-called olfactory epithelium in the nose, which contains the sensory cells that transmit olfactory information to our brain. Animal studies have shown that gene expression in these olfactory cells is altered during a Covid-19 infection and that inflammatory processes predominate. This can be very stressful for those affected: the scent of Christmas fir trees remains hidden from them, as does the taste nuances of their food.

Search for clues in tissue samples

“In most patients with Covid-19-associated smell loss, the body’s normal repair processes restore function soon after the virus is cleared,” writes a research team led by John Finlay of Duke University in Durham. After a week or two, most sufferers can smell and taste again. “It doesn’t work for some people,” says Finlay’s colleague Bradley Goldstein. “We need to better understand why the sense of smell is still impaired in this subgroup of people months to years after infection with Sars-CoV2.”

To do this, the team examined a total of 24 tissue samples from the noses of those who had recovered, including nine from patients who suffered from persistent loss of smell after a Covid 19 infection. The researchers found that no traces of the Covid-19 virus were detectable in any of the samples. However, the samples from the patients who had not regained their sense of smell continued to show an inflammatory response. The analyzes revealed that the tissue was infiltrated by T cells that secrete the inflammatory messenger interferon-gamma. In addition, the composition of other immune cells was also shifted. So-called CD207+ dendritic cells, which are also involved in inflammation, were enriched, while anti-inflammatory M2 macrophages were present to a lesser extent.

Attacked olfactory cells

The number of olfactory neurons was also reduced in people with persistent loss of smell compared to people with a normal sense of smell. The researchers suspect that the reason for this lies in the ongoing attack by the immune system. “The results are amazing,” says Goldstein. “It almost resembles an autoimmune-like process in the nose.” Although the current study focuses on the sense of smell, the researchers believe that similar processes could also play a role in other long-Covid symptoms, including the fatigue and shortness of breath typical of this syndrome and concentration problems.

The new findings can help to develop future treatment methods that eliminate the causes of the loss of odor. “We hope that modulating the abnormal immune response or repair processes in the nose of these patients could help restore at least some of the sense of smell,” Goldstein said. The nose is particularly accessible for treatments, since drugs can be administered locally without causing systemic effects. From the perspective of the researchers, one possibility could therefore be, for example, to locally inhibit the immune cells and thus enable the olfactory cells to regenerate.

Quelle: John Finlay (Duke University, Durham, USA) et al., Science Translational Medicine, doi: 10.1126/scitranslmed.add0484

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