Post-COVID patients with persistent olfactory dysfunction show dysregulated expression of key metabolic pathways in the nasal epithelium

Introduction

Olfactory dysfunction (OD) is common after COVID-19. The underlying mechanism of this impairment is linked to molecular changes that can be studied using single-cell RNA sequencing (scRNA-seq). The aim of this study was to evaluate metabolic pathways (MPs) to find significant differences in patients with and without OD after COVID-19.

Material/method

scRNA-seq was performed on nasal biopsy samples (n=29) from clinically well-characterised patients with/without permanent OD persisting for more than 3 months. All subjects completed a health status questionnaire. Olfactory function was assessed using the Sniffin' Sticks test. Statistical analysis on 2306 MPs was performed.

Results

The study included 13 females and 16 males with a mean age of 42.9 years (SD=13.1). Samples contained a total of 56,624 cells. Statistically significantly (p<0.01) regulated MPs between OD and non-OD participants were classified into the following groups: dysregulated protein biosynthesis, cell cycle metabolism with regenerative function, olfactory signalling, cellular immune response and cellular bioenergetics. Significant disturbances were observed in pathways involved in transmitting signals to neurons. Aside from that dysregulated pathways involved in protein metabolism and apoptosis were identified.

Discussion

The disruption of key MPs indicates a disturbance in the olfactory signal transduction, an impaired regenerative capacity of receptors, and a failure to regenerate epithelial cells, resulting in a dysfunctional mucosal barrier and impaired neurosignalling. Understanding the molecular mechanisms underlying OD is crucial for the development of preventive and therapeutic strategies to restore olfactory function in post-COVID patients.

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