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代谢组学在新型冠状病毒肺炎诊断与预后中的应用

Metabolomics in the Diagnosis and Prognosis of COVID-19.

作者信息

Hasan Mohammad Rubayet, Suleiman Mohammed, Pérez-López Andrés

机构信息

Department of Pathology, Sidra Medicine, Doha, Qatar.

Weill Cornell Medical College in Qatar, Doha, Qatar.

出版信息

Front Genet. 2021 Jul 23;12:721556. doi: 10.3389/fgene.2021.721556. eCollection 2021.

Abstract

Coronavirus disease 2019 (COVID-19) pandemic triggered an unprecedented global effort in developing rapid and inexpensive diagnostic and prognostic tools. Since the genome of SARS-CoV-2 was uncovered, detection of viral RNA by RT-qPCR has played the most significant role in preventing the spread of the virus through early detection and tracing of suspected COVID-19 cases and through screening of at-risk population. However, a large number of alternative test methods based on SARS-CoV-2 RNA or proteins or host factors associated with SARS-CoV-2 infection have been developed and evaluated. The application of metabolomics in infectious disease diagnostics is an evolving area of science that was boosted by the urgency of COVID-19 pandemic. Metabolomics approaches that rely on the analysis of volatile organic compounds exhaled by COVID-19 patients hold promise for applications in a large-scale screening of population in point-of-care (POC) setting. On the other hand, successful application of mass-spectrometry to detect specific spectral signatures associated with COVID-19 in nasopharyngeal swab specimens may significantly save the cost and turnaround time of COVID-19 testing in the diagnostic microbiology and virology laboratories. Active research is also ongoing on the discovery of potential metabolomics-based prognostic markers for the disease that can be applied to serum or plasma specimens. Several metabolic pathways related to amino acid, lipid and energy metabolism were found to be affected by severe disease with COVID-19. In particular, tryptophan metabolism via the kynurenine pathway were persistently dysregulated in several independent studies, suggesting the roles of several metabolites of this pathway such as tryptophan, kynurenine and 3-hydroxykynurenine as potential prognostic markers of the disease. However, standardization of the test methods and large-scale clinical validation are necessary before these tests can be applied in a clinical setting. With rapidly expanding data on the metabolic profiles of COVID-19 patients with varying degrees of severity, it is likely that metabolomics will play an important role in near future in predicting the outcome of the disease with a greater degree of certainty.

摘要

2019年冠状病毒病(COVID-19)大流行引发了全球前所未有的努力,以开发快速且廉价的诊断和预后工具。自严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的基因组被发现以来,通过逆转录定量聚合酶链反应(RT-qPCR)检测病毒RNA在通过早期检测和追踪疑似COVID-19病例以及筛查高危人群来防止病毒传播方面发挥了最重要的作用。然而,基于SARS-CoV-2 RNA或蛋白质或与SARS-CoV-2感染相关的宿主因子的大量替代检测方法已经被开发和评估。代谢组学在传染病诊断中的应用是一个不断发展的科学领域,COVID-19大流行的紧迫性推动了这一领域的发展。依赖于分析COVID-19患者呼出的挥发性有机化合物的代谢组学方法有望应用于即时检测(POC)环境下的大规模人群筛查。另一方面,成功应用质谱法检测鼻咽拭子标本中与COVID-19相关的特定光谱特征可能会显著节省诊断微生物学和病毒学实验室中COVID-19检测的成本和周转时间。关于发现可应用于血清或血浆标本的基于代谢组学的潜在疾病预后标志物的积极研究也在进行中。发现与氨基酸、脂质和能量代谢相关的几种代谢途径受到COVID-19重症疾病的影响。特别是,在几项独立研究中,通过犬尿氨酸途径的色氨酸代谢持续失调,表明该途径的几种代谢物如色氨酸、犬尿氨酸和3-羟基犬尿氨酸作为该疾病潜在预后标志物的作用。然而,在这些检测方法能够应用于临床之前,检测方法的标准化和大规模临床验证是必要的。随着关于不同严重程度的COVID-19患者代谢谱的数据迅速扩展,代谢组学很可能在不久的将来在更确定地预测疾病结果方面发挥重要作用。

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