Millions of people who have lost their sense of smell after contracting Covid may have an ongoing, abnormal immune response that destroys cells in the nose, researchers say.
Doctors analyzed nasal tissue from Covid patients and found that those with long-term olfactory problems had inflammatory immune cells inside the delicate nasal lining that potentially destroyed vital sensory nerve cells.
Dr. Bradley Goldstein, associate professor of neurobiology at Duke University in North Carolina, said the nasal mucosa tissue “contains unique immune cells producing inflammatory signals combined with fewer olfactory nerve cells.” The abnormal immune response was only observed in patients whose loss of smell persisted for months.
“There seems to be an unresolved local immune response that the delicate olfactory cells see,” he added.
Since doctors have noticed that many Covid patients have lost their sense of smell, it has been unclear whether the virus damages sensory cells in the nose, the areas of the brain that process olfactory information, or both.
The researchers examined biopsied tissue from the nasal mucosa of 24 Covid patients, including nine who had lost their sense of smell for at least four months. Tissue from the latter group revealed that T cells involved in inflammation infiltrated the nasal mucosa, where olfactory nerve cells reside. The abnormal immune response was seen even though the patients had no detectable Covid virus, suggesting it persists after the infection has cleared.
When the researchers looked at the number of sensory nerve cells involved in smell, they found that those who suffered long-term loss of smell had significantly fewer, possibly because the delicate tissue of the nasal mucosa was damaged by T-cell inflammation. Such wayward immune responses could explain other symptoms of prolonged Covid, Goldstein said.
At least 5% of people who lose their sense of smell during a Covid infection do not regain their sense quickly or completely, which equates to about 15 million people worldwide, researchers reported in the BMJ this year. “Right now, we don’t have specific, effective treatments,” Goldstein said. “To develop therapies, we need to understand the pathobiology of the problem: what is damaged and where.”
Writing in Science Translational Medicine, the researchers explain how the findings could pave the way for new treatments for post-Covid loss of smell. One possibility is to block the immune cells causing the inflammation locally in the lining of the nose, a part of the body that is easily accessible with creams and sprays. “We are encouraged by these findings and hopeful that new treatments may emerge,” Goldstein said.
Danny Altman, professor of immunology at Imperial College London, said the work was “an important addition to decoding the many pathological tricks of Sars-CoV-2”.
“As we’ve seen before, profound symptomatic changes can occur in the absence of live virus being detected at the scene,” he said. “Loss of smell is one of the key mysteries, and these findings offer an answer, along with previous findings about changes in the olfactory bulb in the nervous system.”
“In patients with Covid-19, persistent olfactory problems have been shown to be linked to the shrinkage of the areas of the brain associated with our sense of smell,” said Dr Gwenaëlle Douaud, a neuroscientist who has studied the effects of Covid on the brain at the University of Oxford . “Inflammatory processes are known to occur in the brain following Sars-Cov-2 infection, regardless of the presence of the virus itself, and this biopsy study now provides further evidence that such specific brain loss may be associated with persistent inflammation and loss of olfactory neurons in the nasal cavity itself.
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