Evaluation of Olfactory Function Through Smell Testing and Nasal Brushing in Patients With COVID-associated Chemosensory Dysfunction and Recovery
Beyzanur Ergun1, Alefiya Albers2, Colin Magdamo2, Hengbin Zhang2, Ji-Hyeon Shin2, Dante Minichetti4, Priyanka Sinha3, Omar Milstein3, Rohan Bhukar2, Zeynep Agirman3, Marina Avetisyan3, Holbrook Eric3, Lora Bankova5, Mark Albers3
1Neurology, LSU Health Shreveport, 2Neurology, Massachusetts General Hospital, 3Massachusetts General Hospital, 4Neurology, Massachusetts General Brigham Hospital, 5Massachusetts General Brigham Hospital
Objective:

COVID-19 is one of the most significant global public health challenges of the 21st century, affecting millions of individuals worldwide. Chronic chemosensory dysfunction (CSD) is prominent manifestation of SARS-CoV-2 infection and remains significant concern for clinicians and patients. 

Background:
In this study, we administered objective olfactory testing and endoscope-guided brushing of the olfactory epithelium to participants. 
Design/Methods:

90 participants with history of chronic-CSD associated with Covid-19 (representing 27 of 50 states) were recruited. Participants self-administered olfactory testing over a 6-week interval that measured odor intensity, identification, confidence, and discrimination. Samples were collected via endoscope-guided nasal brushing of olfactory epithelium. [Recovered-CSD (n=2), Persistent-CSD (n=2), healthy controls (n=2)]. We used regression models to predict olfactory function from clinical history and CSD status. Single-cell transcriptomic analyses were performed on OE samples to investigate cellular composition, gene expression, and intercellular signaling

Results:

Comparisons of olfactory function in the Persistent-CSD group showed deficits across all olfactory measures relative to Recovered-CSD group. The observed deficits were stably maintained after repeat testing 6 weeks later. Comparisons of olfactory function between Recovered-CSD vs healthy participants showed no statistically significant differences. Single-cell analysis revealed significantly reduced ratio of olfactory sensory neurons to sustentacular support cells in persistent CSD, indicating neuronal loss. Transcriptomic analyses in persistent CSD groups identified elevated type-I interferon (IFN-α) signaling in epithelial cells and heightened IFN-γ and cytotoxic programs in T-cells. Gene set enrichment analysis further implicated pro-inflammatory pathways, including TNF–NFκB and IL6–JAK–STAT3.

Conclusions:

Subjective reporting of persistent chemosensory dysfunction in patients with COVID-19 associated CSD are validated by objective psychophysical olfactory testing. Single-cell profiling implicates convergent neuronal loss and persistent, interferon-linked epithelial–immune crosstalk as key drivers of chronic post-COVID smell loss. Molecular analyses of the epithelial cells obtained through nasal brushing demonstrate promising insights about mechanism of chronic CSD and may guide future diagnostic strategies and therapeutic trials.

 

 

 

10.1212/WNL.0000000000215403
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