The inflammatory mechanism could also help explain other long COVID-19 symptoms
Duke University Medical Center
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, a team of scientists led by Duke Health report.
The finding, publishing online Dec. 21 in the
journal Science Translational Medicine, provides an important
insight into a vexing problem that has plagued millions who have not fully
recovered their sense of smell after COVID-19.
While focusing on the loss smell, the finding
also sheds light on the possible underlying causes of other long COVID-19
symptoms -- including generalized fatigue, shortness of breath, and brain fog
-- that might be triggered by similar biological mechanisms.
"One of the first symptoms that has
typically been associated with COVID-19 infection is loss of smell," said
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.
"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," Goldstein said. "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."
In the study, Goldstein and colleagues at
Duke, Harvard and the University of California-San Diego analyzed olfactory
epithelial samples collected from 24 biopsies, including nine patients
suffering from long-term smell loss following COVID-19.
This biopsy-based approach -- using
sophisticated single-cell analyses in collaboration with Sandeep Datta, M.D.,
Ph.D., at Harvard University -- revealed widespread infiltration of T-cells
engaged in an inflammatory response in the olfactory epithelium, the tissue in
the nose where smell nerve cells are located. This unique inflammation process
persisted despite the absence of detectable SARS-CoV-2 levels.
Additionally, the number of olfactory sensory
neurons were diminished, possibly due to damage of the delicate tissue from the
ongoing inflammation.
"The findings are striking,"
Goldstein said. "It's almost resembling a sort of autoimmune-like process
in the nose."
Goldstein said learning what sites are
damaged and what cell types are involved is a key step toward beginning to
design treatments. He said 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," Goldstein
said, noting this work is currently underway in his lab.
He said the findings from this study could
also inform additional research into other long-COVID-19 symptoms that might be
undergoing similar inflammatory processes.
In addition to Goldstein and Datta, study
authors include John B. Finlay, David H. Brann, Ralph Abi-Hachem, David W.
Jang, Allison D. Oliva, Tiffany Ko, Rupali Gupta, Sebastian A. Wellford, E.
Ashley Moseman, Sophie S. Jang, Carol H. Yan, Hiroaki Matusnami, and Tatsuya
Tsukahara.
The study received funding support from the National Institutes of Health (DC018371, DC016859, AG074324, DC019956) and the Duke Department of Head and Neck Surgery & Communication Sciences.