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Integrative modeling of plasma metabolic and lipoprotein biomarkers of SARS-CoV-2 infection in Spanish and Australian COVID-19 patient cohorts

Masuda, R., Lodge, S., Nitschke, P., Spraul, M., Schaefer, H., Bong, S-H, Kimhofer, T., Hall, D., Loo, R.L., Bizkarguenaga, M., Bruzzone, C., Gil-Redondo, R., Embade, N., Mato, J.M., Holmes, E., Wist, J., Millet, O. and Nicholson, J.K. (2021) Integrative modeling of plasma metabolic and lipoprotein biomarkers of SARS-CoV-2 infection in Spanish and Australian COVID-19 patient cohorts. Journal of Proteome Research, 20 (8). pp. 4139-4152.

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Quantitative plasma lipoprotein and metabolite profiles were measured on an autonomous community of the Basque Country (Spain) cohort consisting of hospitalized COVID-19 patients (n = 72) and a matched control group (n = 75) and a Western Australian (WA) cohort consisting of (n = 17) SARS-CoV-2 positives and (n = 20) healthy controls using 600 MHz 1H nuclear magnetic resonance (NMR) spectroscopy. Spanish samples were measured in two laboratories using one-dimensional (1D) solvent-suppressed and T2-filtered methods with in vitro diagnostic quantification of lipoproteins and metabolites. SARS-CoV-2 positive patients and healthy controls from both populations were modeled and cross-projected to estimate the biological similarities and validate biomarkers. Using the top 15 most discriminatory variables enabled construction of a cross-predictive model with 100% sensitivity and specificity (within populations) and 100% sensitivity and 82% specificity (between populations). Minor differences were observed between the control metabolic variables in the two cohorts, but the lipoproteins were virtually indistinguishable. We observed highly significant infection-related reductions in high-density lipoprotein (HDL) subfraction 4 phospholipids, apolipoproteins A1 and A2,that have previously been associated with negative regulation of blood coagulation and fibrinolysis. The Spanish and Australian diagnostic SARS-CoV-2 biomarkers were mathematically and biologically equivalent, demonstrating that NMR-based technologies are suitable for the study of the comparative pathology of COVID-19 via plasma phenotyping.

Item Type: Journal Article
Murdoch Affiliation(s): Australian National Phenome Center
Centre for Computational and Systems Medicine
Health Futures Institute
Publisher: American Chemical Society
Copyright: © 2021 The Authors.
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