Why loss of smell occurs in long COVID-19?

The inflammatory mechanism could also help explain other long COVID-19 symptoms.


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, a team of scientists led by Duke University Medical Center suggests that the reason some people fail to recover their sense of smell after COVID-19 is linked to an ongoing immune assault on olfactory nerve cells and an associated decline in the number of those cells.

Besides focusing on the sense of smell, the study also highlights possible underlying causes of other long COVID-19 symptoms triggered by similar biological mechanisms.

Senior author Bradley Goldstein, M.D., Ph.D., associate professor in Duke’s Department of Head and Neck Surgery and Communication Sciences and the Department of Neurobiology, said, “One of the first symptoms that have typically been associated with COVID-19 infection is loss of smell.”

“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 understand better why this subset of people will continue to have persistent smell loss for months to years after being infected with SARS-CoV2.”

The study examined olfactory epithelium samples from 24 biopsies, including nine patients with long-term smell loss that could be objectively measured following COVID-19. The olfactory epithelium, the tissue in the nose where smell nerve cells are located, was extensively infiltrated with T-cells involved in an inflammatory response, according to this biopsy-based method. Even though there were no detectable quantities of SARS-CoV-2, this particular inflammatory process continued.

Additionally, there were fewer olfactory sensory neurons, probably due to chronic inflammation damaging the sensitive tissue.

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

“Learning what sites are damaged and what cell types are involved is a key step toward beginning to design treatments. The researchers were encouraged that neurons appeared to maintain some ability to repair even after the long-term immune onslaught.”

“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.”

“The findings from this study could also inform additional research into other long-COVID-19 symptoms that might be undergoing similar inflammatory processes.”

Journal Reference:

  1. John Finlay, David Branin, et al. Persistent post–COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium. Science Translational Medicine. DOI: 10.1126/scitranslmed.add0484


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