Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

Diffusion and relaxation edited Proton NMR Spectroscopy of plasma reveals a High-Fidelity supramolecular biomarker signature of SARS-CoV-2 infection

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, M., Holmes, E. and 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). pp. 3976-3986.

PDF - Published Version
Download (3MB) | Preview
Free to read:
*No subscription required


We have applied nuclear magnetic resonance spectroscopy based plasma phenotyping to reveal diagnostic molecular signatures of SARS-CoV-2 infection via combined diffusional and relaxation editing (DIRE). We compared plasma from healthy age-matched controls (n = 26) with SARS-CoV-2 negative non-hospitalized respiratory patients and hospitalized respiratory patients (n = 23 and 11 respectively) with SARS-CoV-2 rRT-PCR positive respiratory patients (n = 17, with longitudinal sampling time-points). DIRE data were modelled using principal component analysis and orthogonal projections to latent structures discriminant analysis (O-PLS-DA), with statistical cross-validation indices indicating excellent model generalization for the classification of SARS-CoV-2 positivity for all comparator groups (area under the receiver operator characteristic curve = 1). DIRE spectra show biomarker signal combinations conferred by differential concentrations of metabolites with selected molecular mobility properties. These comprise the following: (a) composite N-acetyl signals from α-1-acid glycoprotein and other glycoproteins (designated GlycA and GlycB) that were elevated in SARS-CoV-2 positive patients [p = 2.52 × 10–10 (GlycA) and 1.25 × 10–9 (GlycB) vs controls], (b) two diagnostic supramolecular phospholipid composite signals that were identified (SPC-A and SPC-B) from the –+N–(CH3)3 choline headgroups of lysophosphatidylcholines carried on plasma glycoproteins and from phospholipids in high-density lipoprotein subfractions (SPC-A) together with a phospholipid component of low-density lipoprotein (SPC–B). The integrals of the summed SPC signals (SPCtotal) were reduced in SARS-CoV-2 positive patients relative to both controls (p = 1.40 × 10–7) and SARS-CoV-2 negative patients (p = 4.52 × 10–8) but were not significantly different between controls and SARS-CoV-2 negative patients. The identity of the SPC signal components was determined using one and two dimensional diffusional, relaxation, and statistical spectroscopic experiments. The SPCtotal/GlycA ratios were also significantly different for control versus SARS-CoV-2 positive patients (p = 1.23 × 10–10) and for SARS-CoV-2 negatives versus positives (p = 1.60 × 10–9). Thus, plasma SPCtotal and SPCtotal/GlycA are proposed as sensitive molecular markers for SARS-CoV-2 positivity that could effectively augment current COVID-19 diagnostics and may have value in functional assessment of the disease recovery process in patients with long-term symptoms.

Item Type: Journal Article
Murdoch Affiliation(s): Australian National Phenome Center
Health Futures Institute
Publisher: American Chemical Society
Copyright: © 2021 The Authors.
United Nations SDGs: Goal 3: Good Health and Well-Being
Item Control Page Item Control Page


Downloads per month over past year