PDF(Pubmed)
Abstract：
There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were performed on peripheral blood mononuclear cells. Inflammatory mediators in plasma were measured by ELISA and MSD, and clinical information from hospitalised COVID-19 patients (N=15) at admission was included in the analysis. Further, we reanalysed two publicly available datasets: (1) lung tissue RNA-sequencing dataset (N=5) and (2) proteomics dataset from PBCM. ECM remodelling pathways were enriched in PBMC from COVID-19 patients compared to healthy controls. Patients treated at the intensive care unit (ICU) expressed distinct ECM remodelling gene profiles compared to patients in the hospital ward. Several markers were strongly correlated to immune cell subsets, and the dysregulation in the ICU patients was positively associated with plasma levels of inflammatory cytokines and negatively associated with B-cell activating factors. Finally, our analysis of publicly accessible datasets revealed (i) an augmented ECM remodelling signature in inflamed lung tissue compared to non-inflamed tissue and (ii) proteomics analysis of PBMC from severe COVID-19 patients demonstrated an up-regulation in an ECM remodelling pathway. Our results may suggest the presence of an interaction between ECM remodelling, inflammation, and immune cells, potentially initiating or perpetuating pulmonary pathology in severe COVID-19.
摘要：
细胞外基质（ECM）重塑与炎症之间存在相互关系，这可能在严重COVID-19的进展中起作用。为了探索COVID-19中免疫驱动的ECM重塑，我们在这项探索性研究中分析了住院COVID-19患者中的这些相互作用。对外周血单核细胞进行RNA测序和流式细胞分析。通过ELISA和MSD测量血浆中的炎症介质，入院时住院COVID-19患者(N=15)的临床信息被纳入分析.Further,我们重新分析了两个公开的数据集:(1)肺组织RNA测序数据集(N=5)和(2)来自PBCM的蛋白质组学数据集.与健康对照组相比，COVID-19患者的PBMC中富含ECM重塑途径。与医院病房的患者相比，在重症监护病房（ICU）接受治疗的患者表达了不同的ECM重塑基因谱。一些标志物与免疫细胞亚群密切相关，ICU患者的调节异常与血浆炎性细胞因子水平呈正相关，与B细胞活化因子呈负相关。最后,我们对可公开获取的数据集的分析显示:(i)与非发炎组织相比,发炎肺组织的ECM重塑特征增强;(ii)重症COVID-19患者PBMC的蛋白质组学分析显示ECM重塑途径上调.我们的结果可能表明ECM重塑之间存在相互作用，炎症,和免疫细胞，在严重的COVID-19中可能引发或延续肺部病理。
