Gene expression and gray matter volume changes in Post-COVID-19 olfactory dysfunction: a transcriptomic-neuroimaging...

Area of Science:

• Neuroscience
• Genomics
• Otolaryngology

Background:

• Post-COVID-19 olfactory dysfunction (PCOD) is a common sequela of SARS-CoV-2 infection.
• Structural brain alterations have been observed in PCOD patients, but molecular mechanisms are poorly understood.

Purpose of the Study:

• To investigate the relationship between gray matter volume (GMV) changes and gene expression patterns in patients with PCOD.
• To identify specific biological pathways and cell types involved in the pathophysiology of PCOD.

Main Methods:

• 36 PCOD patients and 40 healthy controls underwent olfactory psychophysical testing (Sniffin' Sticks) and visual analogue scale (VAS) assessment.
• Gray matter volume (GMV) was analyzed across 34 brain regions.
• Spearman's correlation, partial least squares regression (PLS), and gene set enrichment analysis were employed.

Main Results:

• PCOD patients exhibited increased GMV in the entorhinal cortex, positively correlated with olfactory function scores (VAS and Sniffin' Sticks).
• PLS analysis revealed significant associations between regional GMV changes and specific gene expression patterns.
• Enrichment analysis identified "inorganic ion transmembrane transport" and "regulation of protein transport" as key biological processes, with high gene expression in GABAergic neurons.

Conclusions:

• Altered brain structure in PCOD is mechanistically linked to specific gene expression profiles.
• The findings highlight the role of inorganic ion and protein transport pathways, and GABAergic neurons in PCOD pathophysiology.
• This study provides novel insights into the molecular underpinnings of olfactory dysfunction following COVID-19.