Gene Expression Profiles in COVID-19-associated Tracheal Stenosis Indicate Persistent Anti-viral Response and Dysregulated Retinol Metabolism

Overview

Journal BMC Res Notes

Publisher Biomed Central

Specialties Biology
General Medicine

Date 2024 May 16

PMID 38755665

Authors

Russell Seth Martins

Joanna Weber

Kostantinos Poulikidis

Al Haitham Al Shetawi

M Jawad Latif

Syed Shahzad Razi

Robert S Lebovics

Faiz Y Bhora

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Identifying Molecular Pathophysiology and Potential Therapeutic Options in Iatrogenic Tracheal Stenosis.

Martins R, Weber J, Johnson B, Luo J, Poulikidis K, Latif M Biomedicines. 2024; 12(6).

PMID: 38927530 PMC: 11201234. DOI: 10.3390/biomedicines12061323.

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