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鉴定与COVID-19疾病严重程度相关的基于外周血单核细胞的分子特征。

Identification of PBMC-based molecular signature associational with COVID-19 disease severity.

作者信息

Shaath Hibah, Alajez Nehad M

机构信息

College of Health & Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), Doha, Qatar.

Translational Cancer and Immunity Center (TCIC), Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), PO Box 34110, Doha, Qatar.

出版信息

Heliyon. 2021 May;7(5):e06866. doi: 10.1016/j.heliyon.2021.e06866. Epub 2021 Apr 20.

Abstract

The longevity of COVID-19 as a global pandemic, and the devastating effects it has had on certain subsets of individuals thus far has highlighted the importance of identifying blood-based biomarkers associated with disease severity. We employed computational and transcriptome analyses of publicly available datasets from PBMCs from 126 patients with COVID-19 admitted to ICU (n = 50), COVID-19 not admitted to ICU (n = 50), non-COVID-19 admitted to ICU (n = 16) and non-COVID-19 not admitted to ICU (n = 10), and utilized the Gencode V33 assembly to analyze protein coding mRNA and long noncoding RNA (lncRNA) transcriptomes in the context of disease severity. Our data identified several aberrantly expressed mRNA and lncRNA based biomarkers associated with SARS-CoV-2 severity, which in turn significantly affected canonical, upstream, and disease functions in each group of patients. Immune, interferon, and antiviral responses were severely suppressed in COVID-19 patients admitted to ICU versus those who were not admitted to ICU. Our data suggests a possible therapeutic approach for severe COVID-19 through administration of interferon therapy. Delving further into these biomarkers, roles and their implications on the onset and disease severity of COVID-19 could play a crucial role in patient stratification and identifying varied therapeutic options with diverse clinical implications.

摘要

新冠疫情作为一场全球大流行疾病持续的时间之长,以及它迄今为止对某些特定人群造成的毁灭性影响,凸显了识别与疾病严重程度相关的血液生物标志物的重要性。我们对来自126例新冠患者(其中50例入住重症监护病房,50例未入住重症监护病房)、16例非新冠入住重症监护病房患者以及10例非新冠未入住重症监护病房患者的外周血单核细胞(PBMC)的公开可用数据集进行了计算和转录组分析,并利用Gencode V33组装在疾病严重程度的背景下分析蛋白质编码mRNA和长链非编码RNA(lncRNA)转录组。我们的数据确定了几种与新冠病毒严重程度相关的异常表达的基于mRNA和lncRNA的生物标志物,这些生物标志物进而显著影响了每组中的经典、上游和疾病功能。与未入住重症监护病房的新冠患者相比,入住重症监护病房的新冠患者的免疫、干扰素和抗病毒反应受到严重抑制。我们的数据表明,通过给予干扰素治疗,可能为重症新冠患者提供一种治疗方法。进一步深入研究这些生物标志物、其作用以及它们对新冠发病和疾病严重程度的影响,可能在患者分层以及确定具有不同临床意义的多种治疗选择方面发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6971/8131569/4cd3f798c629/gr1.jpg

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