Toward precision medicine: Inflammatory nasal epithelial transcriptomic profiles in long COVID

Area of Science:

• Respiratory Medicine
• Immunology
• Genetics

Background:

• The role of the nasal epithelium in long COVID (LC) pathophysiology remains largely unknown.
• Investigating nasal epithelial changes offers potential insights into LC mechanisms.

Purpose of the Study:

• To analyze nasal epithelial transcriptomes in long COVID patients.
• To identify pathophysiological mechanisms for improved disease management.

Main Methods:

• Transcriptomic analysis of nasal epithelium from 55 long COVID patients (3-18 months post-infection).
• Cell-type deconvolution, hierarchical clustering, and gene expression analysis.
• Functional validation using CRISPR/Cas9 gene editing in nasal epithelial cells.

Main Results:

• Persistent inflammatory pathways identified in nasal epithelium at 3-18 months post-COVID.
• Transcriptomic and cellular clusters linked to inflammation and ciliogenesis.
• SMURF1 gene was upregulated in patients with pulmonary abnormalities, and its absence reduced pro-inflammatory cytokine release.

Conclusions:

• Nasal epithelium in long COVID exhibits sustained inflammation.
• Upregulated SMURF1 may drive exacerbated inflammation in patients with lung abnormalities.
• Further research into SMURF1's role in long COVID is warranted for clinical applications.