Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity.
Leveraging metabolic modeling to identify functional metabolic alterations associated with COVID-19 disease severity.
复制标题
利用代谢建模来识别与COVID-19疾病严重程度相关的功能性代谢改变。
DOI：
10.1007/s11306-022-01904-9
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发表时间：
2022-07-11
期刊：
影响因子：
3.6
通讯作者：
Papin, J. A.
中科院分区：
文献类型：
--
作者：
Dillard, L. R.;Wase, N.;Ramakrishnan, G.;Park, J. J.;Sherman, N. E.;Carpenter, R.;Young, M.;Donlan, A. N.;Petri, W.;Papin, J. A.
自2020年初新冠肺炎大流行以来，SARS-CoV2已在全球夺走了600多万人的生命，迄今已有超过5.1亿例病例。为了减轻医疗负担，我们必须研究如何防止非急性疾病发展为需要住院的严重感染。为了实现这一目标，我们通过分析84名新冠肺炎阳性的弗吉尼亚大学住院患者的相关血浆代谢组，研究了非急性(门诊)和重症(需要住院)新冠肺炎样本的代谢特征。我们利用监督和非监督机器学习和代谢建模方法来识别预测新冠肺炎疾病严重程度的关键代谢驱动因素。利用代谢途径丰富分析，我们探索了将这些标记物与疾病进展联系起来的潜在代谢机制。非急性新冠肺炎样本中与色氨酸相关的丰富代谢物表明，天然免疫系统炎症反应得到缓解，免疫病理学相关的肺损伤得到预防。严重的新冠肺炎样本中组氨酸和酮相关代谢的增加为研究肌肉骨骼退化导致的肌肉无力和宿主代谢提供了潜在的机械性见解，这些代谢已被SARS-CoV2感染劫持，以增加病毒的复制和侵袭。我们的研究结果强调了在非急性感染中从先天免疫反应和炎症途径抑制到严重新冠肺炎中的猖獗炎症和相关的代谢系统功能障碍的代谢转变。
Since the COVID-19 pandemic began in early 2020, SARS-CoV2 has claimed more than six million lives world-wide, with over 510 million cases to date. To reduce healthcare burden, we must investigate how to prevent non-acute disease from progressing to severe infection requiring hospitalization. To achieve this goal, we investigated metabolic signatures of both non-acute (out-patient) and severe (requiring hospitalization) COVID-19 samples by profiling the associated plasma metabolomes of 84 COVID-19 positive University of Virginia hospital patients. We utilized supervised and unsupervised machine learning and metabolic modeling approaches to identify key metabolic drivers that are predictive of COVID-19 disease severity. Using metabolic pathway enrichment analysis, we explored potential metabolic mechanisms that link these markers to disease progression. Enriched metabolites associated with tryptophan in non-acute COVID-19 samples suggest mitigated innate immune system inflammatory response and immunopathology related lung damage prevention. Increased prevalence of histidine- and ketone-related metabolism in severe COVID-19 samples offers potential mechanistic insight to musculoskeletal degeneration-induced muscular weakness and host metabolism that has been hijacked by SARS-CoV2 infection to increase viral replication and invasion. Our findings highlight the metabolic transition from an innate immune response coupled with inflammatory pathway inhibition in non-acute infection to rampant inflammation and associated metabolic systemic dysfunction in severe COVID-19.
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影响因子：
4.4
作者：
Delattre H;Sasidharan K;Soyer OS
通讯作者：
Soyer OS
影响因子：
8
作者：
Donlan AN;Sutherland TE;Marie C;Preissner S;Bradley BT;Carpenter RM;Sturek JM;Ma JZ;Moreau GB;Donowitz JR;Buck GA;Serrano MG;Burgess SL;Abhyankar MM;Mura C;Bourne PE;Preissner R;Young MK;Lyons GR;Loomba JJ;Ratcliffe SJ;Poulter MD;Mathers AJ;Day AJ;Mann BJ;Allen JE;Petri WA Jr
通讯作者：
Petri WA Jr
影响因子：
4.4
作者：
Kimhofer, Torben;Lodge, Samantha;Nicholson, Jeremy K.
通讯作者：
Nicholson, Jeremy K.
影响因子：
8.4
作者：
Amzat, Jimoh;Aminu, Kafayat;Danjibo, Maryann C.
通讯作者：
Danjibo, Maryann C.
DOI：
10.1126/science.aat3987
发表时间：
2020-05-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Knudsen NH;Stanya KJ;Hyde AL;Chalom MM;Alexander RK;Liou YH;Starost KA;Gangl MR;Jacobi D;Liu S;Sopariwala DH;Fonseca-Pereira D;Li J;Hu FB;Garrett WS;Narkar VA;Ortlund EA;Kim JH;Paton CM;Cooper JA;Lee CH
通讯作者：
Lee CH