Why we lose our smell – COVID-19


In a recent study, researchers found a connection between a persistent immune attack on olfactory nerve cells and a corresponding drop in the number of those cells and the failure of certain persons to recover their sense of smell following COVID-19.

The discovery offers insight on the potential molecular pathways that may be responsible for additional extended COVID-19 symptoms, such as widespread weariness, shortness of breath, and brain fog, in addition to the lost scent.

Nine individuals with COVID-19-related long-term smell loss were included in the study by Goldstein and colleagues from Duke, Harvard, and the University of California-San Diego. They examined olfactory epithelial samples taken from 24 biopsies.

The olfactory epithelium, the tissue in the nose where the smell nerve cells are situated, was shown to have a broad infiltration of T-cells involved in an inflammatory response after a biopsy and single-cell studies (Figure 1) in conjunction with were performed. Despite the absence of measurable SARS-CoV-2 levels, this inflammatory process remained. Additionally, there were fewer olfactory sensory neurons, probably because of chronic inflammation damaging the sensitive tissue.

Figure 1: T cell infiltrates in nasal olfactory epithelial biopsies from PASC hyposmic patients. (A) Representative immunohistochemistry images of nasal biopsy tissue from normosmic non–COVID-19, normosmic post–COVID-19, or PASC hyposmic individuals. Tissue sections were immunostained for the TUJ1 neuronal marker, CD45 pan-immune cell marker, CD3 T cell marker, and CD68 myeloid cell marker. PASC hyposmic tissue showed dense CD45+ immune cell infiltration, including prominent CD3+ lymphocytic infiltration, which was absent in the normosmic groups; scattered CD68+ cells were present in all conditions. (B) Enlarged area (yellow box) from (A) shows CD3+ lymphocytes, with prominent infiltration into the olfactory epithelium (white arrows); dashed white line marks the basal lamina. Scale bar, 50 μm. (C) Additional nasal biopsies were processed for scRNA-seq to permit quantitative analyses. Uniform manifold approximation projection (UMAP) visualization of combined PASC hyposmic and control normosmic scRNA-seq datasets integrating 16 human nasal biopsies permitted robust cell cluster analysis and annotation. RBCs, red blood cells; pDC, plasmacytoid DCs.

They are hoping that controlling these patients’ aberrant immune responses or nose-related healing processes would at least partially help them regain their sense of smell. They said that further research on other long-COVID-19 symptoms that could be experiencing comparable inflammatory processes could benefit from the study’s findings.

Journal article: Finlay, J.B., et al. 2022. Persistent post–COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium. Science Translational Medicine.

Summary by Stefan Botha


International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineElizabeth Glazer Pediatric Aids Foundation