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The following is a summary of “Towards precision medicine: inflammatory nasal epithelial transcriptomic profiles in long COVID,” published in the June 2025 issue of Journal of Allergy and Clinical Immunology by Baalbaki et al.
Researchers conducted a retrospective study to examine nasal epithelial transcriptomes in individuals with long COVID (LC) to explore underlying pathophysiological mechanisms for disease management.
They used data from the ‘Precision Medicine for more Oxygen’ (P4O2) COVID-19 cohort, collecting medical records and nasal epithelial transcriptomes at 3–6 months (n=40) and 12–18 months (n=15) after infection. Cell type proportions were inferred using deconvolution based on a single-cell dataset. Hierarchical clustering was applied to define transcriptomic and cellular clusters, and gene expression patterns, gene set enrichment, and related pulmonary traits were an3ealyzed. Functional validation involved CRISPR-Cas9 gene editing and in vitro assays using primary nasal epithelial cells with targeted mutations. Gene expression in LC cases was compared to healthy controls (n=51).
The results showed that at 3–6 and 12–18 months post-COVID, transcriptomes were linked to inflammatory pathways (padj<0.05). Distinct transcriptomic and cellular clusters associated with inflammation and ciliogenesis were identified (padj<0.05). Comparison between individuals with and without pulmonary radiological abnormalities revealed 613 differentially expressed genes (padj<0.05), with increased expression of inflammatory genes in those with abnormalities. The SMURF1 levels were significantly higher in individuals with abnormalities than in those without and in healthy controls. Nasal epithelial cells lacking SMURF1 (SMURF1-/- ) produced lower amounts of pro-inflammatory cytokines following viral exposure compared to control cells (P<0.05).
Investigators concluded that the nasal epithelium in LC exhibited sustained inflammation, with SMURF1 upregulation potentially contributing to heightened inflammatory responses in individuals with radiological abnormalities.
Source: jacionline.org/article/S0091-6749(25)00618-9/fulltext
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