A continual and abnormal immune response that destroys nasal cells could be responsible for millions of people losing their sense of smell after contracting Covid, say researchers, who found that the unusual response had been seen even in some patients having no detectable signs of the virus.
Doctors analysed nasal tissue from Covid patients and found that those with long-term problems with their sense of smell had inflammation-driving immune cells inside the delicate nasal lining, which were probably killing vital sensory nerve cells.
The Guardian reports that Dr Bradley Goldstein, an associate professor in neurobiology at Duke University in North Carolina, said tissue from the lining of the nose “contained unique immune cells producing inflammatory signals, combined with fewer olfactory nerve cells”. The unusual immune response was seen only in patients whose loss of smell persisted for months.
“It appears that there is an unresolved local immune response, which the delicate olfactory cells are seeing,” he added.
Since doctors started to notice that Covid patients lost their sense of smell, it has been unclear whether the virus damages sensory cells in the nose, areas of the brain that process olfactory information, or both.
The researchers studied biopsied tissue from the nasal lining 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 had infiltrated the nasal lining where smell nerve cells are found.
The unusual immune response was seen despite the patients having no detectable Covid virus, suggesting it was persisting after the infection had been 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 notably fewer, possibly because the delicate tissue of the nasal lining had been damaged by the T-cell-driven inflammation. Similar wayward immune responses might explain other symptoms of long Covid, Goldstein said.
At least 5% of people who lose their sense of smell during a Covid infection do not recover the sense quickly or fully, amounting to about 15m people globally, researchers reported last year. “Currently, we have no specific, effective treatments,” said Goldstein. “To develop therapies, we need to understand the pathobiology of the problem: what is damaged and where.”
Writing in Science Translational Medicine, the researchers said the findings might pave the way for new treatments for post-Covid loss of smell. One option is to block inflammation-driving immune cells locally in the nasal lining, a part of the body that is easy to reach with creams and sprays. “We are encouraged by these findings and hope new treatments may emerge,” said Goldstein.
Danny Altmann, professor of immunology at Imperial College London, said the work was an “important addition to decoding the many pathological ploys of Sars-CoV-2”.
“As we’ve seen before, profound symptomatic changes can occur in the absence of live virus detectable at the scene,” he said. “The loss of smell has been one of the key mysteries and these findings offer an answer, along with previous findings of changes to the olfactory bulb in the nervous system.”
“In Covid-19 patients, persistent olfactory problems have been shown to be associated with the shrinking of brain regions related to 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 be ongoing in the brain after Sars-Cov-2 infection, regardless of whether the virus itself is present, and this biopsy study now provides further evidence that such a specific brain loss could be related to persevering inflammation and loss of olfactory neurons in the nasal cavity itself.”
Study details
Persistent post–COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium
John Finlay, David Brann, Ralph Abi Hachem, David Jang, Bradley Goldstein.
Published in Science Translational Medicine on 21 December 2022
Abstract
SARS-CoV-2 causes profound changes in the sense of smell, including total smell loss. Although these alterations are often transient, many patients with COVID-19 exhibit olfactory dysfunction that lasts months to years. Although animal and human autopsy studies have suggested mechanisms driving acute anosmia, it remains unclear how SARS-CoV-2 causes persistent smell loss in a subset of patients. To address this question, we analysed olfactory epithelial samples collected from 24 biopsies, including from nine patients with objectively quantified long-term smell loss after COVID-19. This biopsy-based approach revealed a diffuse infiltrate of T cells expressing interferon-γ and a shift in myeloid cell population composition, including enrichment of CD207+ dendritic cells and depletion of anti-inflammatory M2 macrophages. Despite the absence of detectable SARS-CoV-2 RNA or protein, gene expression in the barrier supporting cells of the olfactory epithelium, termed sustentacular cells, appeared to reflect a response to ongoing inflammatory signaling, which was accompanied by a reduction in the number of olfactory sensory neurons relative to olfactory epithelial sustentacular cells. These findings indicate that T cell–mediated inflammation persists in the olfactory epithelium long after SARS-CoV-2 has been eliminated from the tissue, suggesting a mechanism for long-term post–COVID-19 smell loss.
See more from MedicalBrief archives:
Long-term damaged sense of smell in 50% of 1st wave COVID cases – Karolinska study
Newer COVID variants less likely to affect smell and taste – US study
Association between loss of smell in after SARS-CoV-2 infection and cognitive impairment
French wine tasters ask for vaccine priority to protect sense of smell and taste
Patients report loss of smell in 86% of mild COVID-19 cases — European hospital study