布鲁克’s Molecular Phenomics Research Tools Enable New Insights into ‘Long COVID’ and Post-Acute Metabolic Abnormalities
珀斯，西澳大利亚州 - 2021年5月20日：关于Covid-19的临床研究合作，在19号势转换和随后的现场反应发现了急性血液样本中分子特征的短暂和持续的全身变化，急性血液样本后三个月后阶段。These biochemical abnormalities, identified by a quantitative, label-free assay platform integrating nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), relate to ongoing ‘long COVID’ symptoms, which persist post-acute infection and can affect more than half of the recovered COVID patients - even six months after infection.
A series of seminal papers on the molecular phenome of acute disease and post-acute COVID syndrome in patient plasma has been announced (https://medicalxpress.com/news/2021-05-covid-affecting-patients-months.html) and published (1-5) by the Australian National Phenome Centre (ANPC) at Murdoch University, in collaboration with other academic medical centers, and with Bruker Corporation (Nasdaq: BRKR) as a key technology partner.
综合定量NMR和MS分析平台form, which is for research use only, has revealed metabolic abnormalities, interactions of metabolic markers with cytokines, as well as interactions of lipoproteins with inflammation markers, caused by acute COVID-19. It enabled the creation of a multi-assay panel of pheno-conversion markers that change significantly during disease progression. This molecular phenomics panel can now also provide a measure of a patient’s partial recovery, or of emerging chronic PACS risks, e.g., for new-onset diabetes or for new-onset atherosclerosis, and for other persistent or reoccurring symptoms, including chronic fatigue, ‘brain fog’ and numerous other reported long COVID symptoms.
急性non-hospitalized跟踪研究nd mildly affected COVID-19 patients revealed that the majority of these patients is not back to normal health or normal biochemistry three months on and suffers from PACS, also referred to as ‘Long COVID’, characterized by persistent symptoms and health dysfunction after the acute infection. More than 57% of these patients show one or more symptoms up to six months following the acute phase, and many of them have metabolic abnormalities as revealed by the NMR and MS based pheno-reversion panel.
Professor Jeremy Nicholson, Pro Vice Chancellor for the Health Futures Institute at Murdoch University and Director of the ANPC explained: “Advanced NMR- and MS-screening of blood plasma provides complementary insights into the complex COVID-19 systemic pattern. There were multiple but variable biochemical abnormalities in the follow up patients with a variety of partial recovery phenotypes. We noted that most of the follow up COVID-19 patients had metabolic abnormalities irrespective of whether they were still symptomatic, but symptomatic patients were statistically more likely to have biochemical abnormalities.”
He continued: “This is an immensely dangerous disease that is not only costing lives today, but as we’re discovering now, may have serious health consequences for some patients long into the future, even in relatively mild original cases.”
The majority of patients at three months post-acute phase have a variety of blood metabolic abnormalities that differ between symptomatic and asymptomatic at six months. The researchers found that plasma lipoproteins in the blood of COVID-19 patients changed during infection and came closer to patterns typically found in patients with diabetes and atherosclerosis. Some abnormalities were reduced in the follow up patients and were reversible, whereas markers related to liver, energy metabolism and neuro-pathologies were often not completely reversed.
The latest research is consistent with earlier findings from the ANPC that showed COVID-19 is a systemic disease with multi-organ effects. The concept of pheno-conversion, as expressed in the lipoprotein and metabolic profile of blood plasma, establishes molecular phenotype biomarkers that can be analyzed for disease progression, severity and treatment. This underlines the importance of longitudinal studies on recovered patients for PACS effects and long-term health risks.
ANPC还设计了一种新颖的松弛和扩散编辑的NMR方法，该方法提高了选择性并导致从超分子簇发现了新型的磷脂信号（3）。Nicholson教授补充说：“这是复杂血浆光谱的运动编辑的第一个例子，以增强诊断程序的选择性，并基于分子的动力学以及浓度为其他NMR方法打开了其他NMR方法。”
Dr. Manfred Spraul, the CTO at Bruker BioSpin’s Applied, Industrial and Clinical Division, commented: “These findings underline the potential of our integrated NMR and MS assay platform for risk screening for PACS. Our research methods are robust and transferable for personalized molecular phenome signatures, providing a gateway to better understanding the long-term effects of COVID-19. These molecular phenotype insights are eventually expected to support better post-acute COVID-19 patient management for faster recovery, and a reduction in healthcare costs.”
The COVID-19 pheno-conversion and pheno-reversion signatures are detected by combined NMR and MS assays, providing complementary insights into potential biomarkers for cardiology, metabolism, diabetes, kidney disease, liver function, neurological effects, and inflammation.
布鲁克（Bruker）已开始验证在欧洲设置的这种综合NMR/MS临床研究测定法，其目的是开发PACS个性化的风险筛查和纵向患者监测诊断方法。
Dr. Óscar Millet, Principal Investigator atCIC bioGUNE in Bilbao西班牙，评论说：“作为欧洲精密医学的关键临床研究实验室之一，我们看到了高性能NMR和MS技术支持PACS研究的巨大潜力。我们是由ANPC领导的International Covid-19网络的活跃成员。统一的研究方法基于ANPC和Bruker开发的标准化操作程序，使我们能够研究西班牙患者同类的PAC，并在分析和生物学水平上与ANPC的数据交叉验证我们的数据。”
The studies were conducted using Avance™ IVDr NMR 600 MHz spectrometers integrated in the ANPC class II biosecurity laboratory, together with Bruker and CIC bioGUNE in-vitro diagnostics NMR research (IVDr) technology methods. The ANPC has also equipped its molecular phenomics lab with state-of-the-art mass spectrometers, including Bruker impact II and timsTOF™ Pro QTOF-MS, and a solariX™ MRMS system.
关于澳大利亚国家现象中心
The Australian National Phenome Centre (ANPC), at Murdoch University, will help transform how long and how well people live, not just in Australia, but around the world. The work of the ANPC supports almost every area of bioscience. It reaches across traditional research silos and fosters a new, more collaborative approach to science. Long-term, the ANPC hopes to build ‘global atlases’ of human disease, providing insights into future health risks which everyone on the planet can benefit from. The only facility of its kind in the southern hemisphere, the ANPC brings together other western Australian universities and leading health and medical research institutes. It is linked to the International Phenome Centre Network and also has wide research activities in agriculture and environmental science. The ANPC helps to position Perth and Western Australia as a major leader in precision medicine, and enables quantum leaps in predicting, diagnosing and managing human disease. It is part of the Health Futures Institute at Murdoch University. For more information about the ANPC COVID-19 research, please visit thecorresponding web site。
关于CIC Biogune
位于Bizkaia科学技术园的Biogune研究中心是一个生物医学研究组织，该组织对结构，分子和细胞生物学之间的界面进行了尖端研究，并特别注意疾病分子碱基的研究，以研究疾病的分子碱基。用于开发新的诊断方法和高级疗法。CIC Biogune被认为是“ Severo Ochoa卓越中心”，这是对西班牙卓越中心的最高认可。CIC Biogune配备了用于代谢组分析的最新设施，包括两个IVDR NMR光谱仪和一个Impact II质谱仪。CIC Biogune正在领导一个雄心勃勃的精密医学项目（Akribea），以开发改进的个性化诊断方法。Akribea项目将在几年内针对巴斯克地区（10.000名受试者）的一部分人口，以创建样本/数据存储库以及附属生物群和数据挖掘能力。
关于布鲁克公司（纳斯达克：BRKR）
布鲁克is enabling scientists to make breakthrough discoveries and develop new applications that improve the quality of human life. Bruker’s high performance scientific instruments and high value analytical and diagnostic solutions enable scientists to explore life and materials at molecular, cellular and microscopic levels. In close cooperation with our customers, Bruker is enabling innovation, improved productivity and customer success in life science molecular and cell biology research, in applied and pharma applications, in microscopy and nanoanalysis, as well as in industrial applications. Bruker offers differentiated, high-value life science and diagnostics systems and solutions in preclinical imaging, clinical phenomics research, proteomics and multiomics, spatial and single-cell biology, functional structural and condensate biology, as well as in clinical microbiology and molecular diagnostics. For more information, please visit: www.fatactor.com.
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References
- Kimhofer T, Lodge S, Whiley L et al. Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV‑2 Infection,J Proteome Res 2020 Nov 6; 19（11）：4442-4454
- Lodge S，Nitschke P，Kimhofer T等。NMR Spectroscopic Windows on the Systemic Effects of SARS-CoV-2 Infection on Plasma Lipoproteins and Metabolites in Relation to Circulating Cytokines.Journal of Proteome Research, 2020。20 1382-1396. https://pubs.acs.org/doi/10.1021/acs.jproteome.0c00876
- Lodge S，Nitschke P，Kimhofer T等。2等离子体的扩散和弛豫编辑的质子NMR光谱揭示了SARS-COV-2感染分析化学的高效率超分子生物标志物3，2021年。https://dx.doi.org/10.1021/acs.analchem.0c04952
- Nathan G. Lawler等。与急性SARS-COV-2感染和炎性细胞因子反应相关的胺和Kynurenine代谢的全身性扰动，蛋白质组研究杂志（2021年3月16日）。DOI: 10.1021/acs.jproteome.1c00052
- Elaine Holmes，Julien Wist等。急性阶段的非房屋化COVID-19患者中的不完整的全身恢复和代谢现实：对急性后Covid-19综合征评估的影响，蛋白质组研究杂志（2021年5月19日）。https://pubs.acs.org/doi/10.1021/acs.jproteome.1c00224
这项研究由大三角刀健康研究基金会，麦库斯克基金会和西澳大利亚州政府资助