Gene expression profiles in COVID-19-associated tracheal stenosis indicate persistent anti-viral response and dysregulated retinol metabolism.

Publisher: Biomed Central Country of Publication: England NLM ID: 101462768 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-0500 (Electronic) Linking ISSN: 17560500 NLM ISO Abbreviation: BMC Res Notes Subsets: MEDLINE

Original Publication: London : Biomed Central, 2008.

COVID-19*/genetics ; COVID-19*/metabolism ; COVID-19*/virology ; Vitamin A*/metabolism ; Tracheal Stenosis*/genetics ; Tracheal Stenosis*/metabolism ; Transcriptome*/genetics; Humans ; Female ; Adult ; SARS-CoV-2 ; Gene Expression Profiling/methods ; Trachea/metabolism ; Trachea/virology

Introduction: Coronavirus disease 2019 (COVID-19)-associated tracheal stenosis (COATS) may occur as a result of prolonged intubation during COVID-19 infection. We aimed to investigate patterns of gene expression in the tracheal granulation tissue of patients with COATS, leverage gene expression data to identify dysregulated cellular pathways and processes, and discuss potential therapeutic options based on the identified gene expression profiles.
Methods: Adult patients (age ≥ 18 years) presenting to clinics for management of severe, recalcitrant COATS were included in this study. RNA sequencing and differential gene expression analysis was performed with transcriptomic data for normal tracheal tissue being used as a control. The top ten most highly upregulated and downregulated genes were identified. For each of these pathologically dysregulated genes, we identified key cellular pathways and processes they are involved in using Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) applied via Database for Annotation, Visualization, and Integrated Discovery (DAVID).
Results: Two women, aged 36 years and 37 years, were included. The profile of dysregulated genes indicated a cellular response consistent with viral infection (CXCL11, PI15, CCL8, DEFB103A, IFI6, ACOD1, and DEFB4A) and hyperproliferation/hypergranulation (MMP3, CASP14 and HAS1), while downregulated pathways included retinol metabolism (ALDH1A2, RBP1, RBP4, CRABP1 and CRABP2).
Conclusion: Gene expression changes consistent with persistent viral infection and dysregulated retinol metabolism may promote tracheal hypergranulation and hyperproliferation leading to COATS. Given the presence of existing literature highlighting retinoic acid's ability to favorably regulate these genes, improve cell-cell adhesion, and decrease overall disease severity in COVID-19, future studies must evaluate its utility for adjunctive management of COATS in animal models and clinical settings.
(© 2024. The Author(s).)

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Keywords: Coronavirus disease 2019; Endotracheal intubation; Granulation tissue; Molecular medicine; RNA; Subglottic stenosis

Date Created: 20240516 Date Completed: 20240517 Latest Revision: 20240519

20240519

PMC11100031

10.1186/s13104-024-06775-y

38755665