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Abstract：
BACKGROUND: 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).
CONCLUSIONS: 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.
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).
CONCLUSIONS: 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.
摘要：
背景：2019年冠状病毒病（COVID-19）相关的气管狭窄（COATS）可能是由于COVID-19感染期间长时间插管造成的。我们旨在研究COATS患者气管肉芽组织中的基因表达模式，利用基因表达数据来识别失调的细胞通路和过程，并根据鉴定的基因表达谱讨论潜在的治疗选择。
方法：成年患者（年龄≥18岁）到诊所进行严重，这项研究包括顽固的外套。使用正常气管组织的转录组数据作为对照进行RNA测序和差异基因表达分析。鉴定了前十个高度上调和下调的基因。对于这些病理失调的基因，我们确定了关键的细胞途径和过程，他们参与使用基因本体论（GO）和KEGG（京都基因和基因组百科全书）通过数据库应用注释，可视化,和集成发现（DAVID）。
结果：两名女性，36岁和37岁，包括在内。失调基因的概况表明细胞反应与病毒感染一致（CXCL11，PI15，CCL8，DEFB103A，IFI6，ACOD1和DEFB4A）和过度增殖/超颗粒（MMP3，CASP14和HAS1），而下调途径包括视黄醇代谢（ALDH1A2，RBP1，RBP4，CRABP1和CRABP2）。
结论：与持续性病毒感染和视黄醇代谢失调一致的基因表达变化可能促进气管高颗粒和过度增殖，导致COATS。鉴于现有文献强调视黄酸有利地调节这些基因的能力，改善细胞-细胞粘附，并降低COVID-19的总体疾病严重程度，未来的研究必须评估其在动物模型和临床环境中辅助治疗COATS的效用。
方法：成年患者（年龄≥18岁）到诊所进行严重，这项研究包括顽固的外套。使用正常气管组织的转录组数据作为对照进行RNA测序和差异基因表达分析。鉴定了前十个高度上调和下调的基因。对于这些病理失调的基因，我们确定了关键的细胞途径和过程，他们参与使用基因本体论（GO）和KEGG（京都基因和基因组百科全书）通过数据库应用注释，可视化,和集成发现（DAVID）。
结果：两名女性，36岁和37岁，包括在内。失调基因的概况表明细胞反应与病毒感染一致（CXCL11，PI15，CCL8，DEFB103A，IFI6，ACOD1和DEFB4A）和过度增殖/超颗粒（MMP3，CASP14和HAS1），而下调途径包括视黄醇代谢（ALDH1A2，RBP1，RBP4，CRABP1和CRABP2）。
结论：与持续性病毒感染和视黄醇代谢失调一致的基因表达变化可能促进气管高颗粒和过度增殖，导致COATS。鉴于现有文献强调视黄酸有利地调节这些基因的能力，改善细胞-细胞粘附，并降低COVID-19的总体疾病严重程度，未来的研究必须评估其在动物模型和临床环境中辅助治疗COATS的效用。
