Why some people are unable to regain their sense of smell after getting COVID-19

Since the beginning of the COVID-19 pandemic, profound changes in the sense of smell, including complete loss of smell, have been a significant (and puzzling) symptom of
infection.
Although changes in odor are usually short-lived, many people with COVID-19 have long-term olfactory dysfunction
.
Until now, it is unclear how SARS-CoV-2 infection causes persistent loss of smell in a subset of patients
.

Now, a new study suggests that the reason why some people are unable to regain their sense of smell after COVID-19 is related to
the immune system's continued attack on olfactory nerve cells and the associated decline in the number of these cells.
The study analyzed olfactory epithelial samples collected from 24 biopsies, including 9 patients
who objectively quantified long-term olfactory loss after COVID-19.

This study provides important insights into a thorny problem that has plagued millions of people and has not fully regained their sense of
smell after COVID-19.
While the study focused on olfactory loss, this finding also revealed other potential causes of long-term COVID-19 symptoms, including general fatigue, shortness of breath, and brain fog, which may be triggered by similar biological mechanisms
.

The study, published in the journal Science Translational Medicine, is associated with persistent olfactory loss after COVID-19 and altered gene expression in olfactory epithelial cells
.

Bradley Goldstein, MD, associate professor in the Department of Head and Neck Surgery and Communication Sciences at Duke University School of Medicine, said: "One of the first symptoms often associated with COVID-19 infection is loss
of smell.

"Fortunately, many people who have altered sense of smell during the acute phase of a viral infection will recover their sense of smell within the next one to two weeks, but some will not
," Goldstein said.
"We need to better understand why these people experience loss
of smell for months to years after SARS-CoV2 infection.
"

For the study, Goldstein and colleagues analyzed olfactory epithelial samples collected from 24 biopsies, including nine patients
with long-term olfactory loss due to COVID-19.

Single-cell analysis of biopsies, such as single-cell RNA-seq and immunohistochemistry, reveals extensive infiltration
of T cells involved in the inflammatory response in the olfactory epithelium (nose tissue where olfactory nerve cells are located).
Although no SARS-CoV-2 levels were detected, this unique inflammatory process persisted
.

More specifically, they found "diffuse infiltration of interferon-γ-expressing T cells and changes in the composition of myeloid cell populations, including enrichment of CD207+ dendritic cells and depletion
of anti-inflammatory M2 macrophages.
" ”

The authors add that although no SARS-CoV-2 RNA or protein was detected, gene expression in olfactory epithelial support cells reflects persistent inflammatory signals
.
In addition, the number of olfactory sensory neurons decreases, possibly due to ongoing inflammation that damages the delicate tissue
.

Goldstein said: "These findings are amazing
.
" This is almost similar to an autoimmune process
in the nose.
”

Goldstein says understanding where is damaged and which cell types are involved is a critical step
in starting to design treatments.
He added that the researchers are encouraged that neurons seem to retain some ability to repair even after a prolonged immune attack
.

"We hope that modulating the abnormal immune response or repair process in the nose of these patients can help at least partially restore the sense of
smell," Goldstein said.
He noted that the work is currently underway
in his lab.

The results of this study could also inform further research into other prolonged COVID-19 symptoms that may be experiencing a similar inflammatory process
.