Bruker's Molecular Phenomics Research Tools Enable New Insights into Long COVID and its Post-Infection Disease Effects

Clinical Research Collaboration of Bruker and the Australian National Phenome Centre (ANPC) at Murdoch University Develops Platform for Monitoring and Personalizing The Management of Post-Accute COVID-19 Syndrome (PACS), Colloquically Known as Long COVID.
*For Research Use Only - not for Use in Clinical Diagnostics

PERTH, Western Australia - May 17th, 2021: A long-term scientific co-creation partnership between the Australian National Phenome Centre (ANPC) at Murdoch University and Bruker Corporation (Nasdaq:BRKR) that for one year now focuses on the combat of the COVID-19 pandemic threat has uncovered a persistent systematic changes of molecular signature in COVID-19 patient blood samples 3 months after the acute disease phase(1). These biochemical abnormalities, identified by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), relate to ongoing symptoms post infection. These symptoms affect more than half of patients six months on and include chronic fatigue, muscle and joint pain, loss of sense of smell(4).

This approach has revealed deep metabolic abnormalities, interactions of metabolic markers with cytokines(2) as well as interaction of lipoproteins with inflammation markers, caused by COVID-19. This enabled the creation of a panel of phenoconversion markers generated by both NMR and MS that change significantly during disease progression and can provide a measure of a patient’s systemic recovery.

Post-acute follow up studies on non-hospitalized and midly affected COVID-19 patients revealed that the majority is not back to normal health or normal biochemistry three months on and suffers from PACS or 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 follwoing the acute phase and many of them have metabolic abnormalities as revealed by the NMR and MS based phenoconversion panel(4).

Professor Jeremy Nicholson, Pro Vice Chancellor for the Health Futures Institute at Murdoch University and Director of the ANPC explains: “Advanced NMR- and MS- based screening of human blood plasma provides valuable and 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 has metabolic abnormalities irrespective of whether they were still symptomatic but that symptomatic patients were statistically much more likely to have biochemical abnormalities.”

He continues: “This is an immensely dangerous disease that is not only costing lives today, but as we’re discovering now, may have serous 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 significantly 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. Many of these particular abnormalities were significantly reduced in the follow up patients and were reversible, whereas markers related to liver, energy metabolism and neuropathologies were 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 phenoconversion, as expressed in the lipoprotein and metabolic profile of blood plasma - where an individual’s phenotype changes due to diseases, environmental factors and interventions - establishes molecular phenotype biomarkers that can be analyzed for disease progression, severity and treatment effects. This underlines the importance of longitudinal studies on recovered patients to follow up on the PACS effects and long-term health risks.

ANPC scientists devised a combined relaxation and diffusion edited NMR method that further refined selectivity and led to the discovery of novel phospholipid signals from supramolecular clusters(3). “This is the first example of motional editing of complex blood plasma spectra to enhance the selectivity of a diagnostic procedure and opens the door to other NMR approaches to classification based on the dynamics of molecules, as well as concentrations.” adds Professor Nicholson, who further indicates that, this also gives a novel window on phenoreversion, as current data suggest that some of the immunological drivers of the early chemical pathology were reversed in the non-hospitalized patients.

Professor Nicholson continued: “We are now working on gaining a better understanding of the post-acute phase of COVID-19 reversibility of the patients’ abnormal metabolic profiles (Phenoreversion) and are now actively applying these methods to study long COVID.”

Dr. Manfred Spraul, the CTO at Bruker BioSpin’s Applied, Industrial and Clinical Division, comments: “These findings underline the potential of NMR spectroscopy as a tool for risk screening for PACS. Our methods are robust and transferable with long-term reproducibility for personalized molecular phenome signatures of each patient, providing a gateway to better understanding the long-term effects of COVID-19. These molecular phenotype insights are expected to support better post-acute COVID-19 patient management for faster recovery, and a reduction in healthcare costs.”

The COVID-19 phenoconversion and phenoreversion signatures are detected by combined NMR and MS techniques, providing complementary information. This unique combination gives insights into potential biomarkers relating to cardiology, energy metabolism, diabetes, kidney disease, liver function, neurological effects, and inflammation.

Bruker is planning to further validate this combined NMR/MS methodology and assay set for clinical research, enabling personalized risk screening as well as for longitudinal monitoring in Europe and later on a global scale.

Dr. Óscar Millet, Principal Investigator at CIC bioGUNE in Bilbao, Spain, comments: “As one of the key clinical research labs for precision medicine in Europe we see huge potential for the PACS research enabled by high performance NMR and MS technology. We are an active member of the International COVID-19 research network, which is led by the ANPC. The harmonized research approach, which is based on standardized operating procedures developed by ANPC and Bruker, has allowed us to study PACS on Spanish patient cohorts and cross-validate our data with those of the ANPC at both the analytical and biological level.”

The studies were conducted using Avance™ IVDr NMR 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.

About the Australian National Phenome Centre
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 the corresponding web site.

About CIC bioGUNE
The bioGUNE Research Center, based in the Bizkaia Science and Technology Park, is a biomedical research organization that develops cutting-edge research on the interface between structural, molecular and cellular biology, with special attention to the study of the molecular bases of disease, to be used in the development of new diagnostic methods and advanced therapies. CIC bioGUNE is recognized as a “Severo Ochoa Center of Excellence”, the highest recognition of centers of excellence in Spain. CIC bioGUNE is equipped with state-of-the-art facilities for metabolomic analyses, including two IVDr NMR spectrometers and an Impact II mass spectrometer. CIC bioGUNE is leading an ambitious project in precision medicine (Akribea) to develop improved personalized diagnostic methods. Akribea project will target a segment of the population in the Basque Country (10.000 subjects) during several years to create a sample/data repository and the accessory biobanking and data mining capacities. the Australian National Phenome Centre

About Bruker Corporation (Nasdaq: BRKR)
Bruker 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: https://www.bruker.com.

References

1. Kimhofer, T., Lodge, S., Whiley, L., Gray, N., Loo, R. L., Lawler, N. G., Nitschke, P., Bong, S. H., Morrison, D. L., Begum, S., Richards, T., Yeap, B. B., Smith, C., Smith, K., Holmes, E., & Nicholson, J. K. (2020). Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV-2 Infection. Journal of Proteome Research, 19(11), 4442–4454. https://doi.org/10.1021/acs.jproteome.0c00519

2. Lodge, S., Nitschke, P., Kimhofer, T., Coudert, J. D., Begum, S., Bong, S. H., Richards, T., Edgar, D., Raby, E., Spraul, M., Schaefer, H., Lindon, J. C., Loo, R. L., Holmes, E., & Nicholson, J. K. (2021). 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, 20(2), 1382–1396. https://doi.org/10.1021/acs.jproteome.0c00876

3. Lodge, S., Nitschke, P., Kimhofer, T., Wist, J., Bong, S. H., Loo, R. L., Masuda, R., Begum, S., Richards, T., Lindon, J. C., Bermel, W., Reinsperger, T., Schaefer, H., Spraul, H., Spraul, M., Holmes, E., & Nicholson, J. K. (2021). Diffusion and Relaxation Edited Proton NMR Spectroscopy of Plasma Reveals a High-Fidelity Supramolecular Biomarker Signature of SARS-CoV-2 Infection. Analytical Chemistry, 93(8), 3976-3986. https://doi.org/10.1021/acs.analchem.0c04952

4. Include reference latest JPR paper published today.

This research was funded by Spinnaker Health Research Foundation, The McCusker Foundation and the Western Australian State Government.