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Diffusion and Relaxation Edited Proton NMR Spectroscopy of Plasma Reveals a High-Fidelity Supramolecular Biomarker Signature of SARS-CoV-2 Infection
- Source :
- Analytical Chemistry; March 2021, Vol. 93 Issue: 8 p3976-3986, 11p
- Publication Year :
- 2021
-
Abstract
- We have applied nuclear magnetic resonance spectroscopy based plasma phenotyping to reveal diagnostic molecular signatures of SARS-CoV-2 infection viacombined 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) vscontrols], (b) two diagnostic supramolecular phospholipid composite signals that were identified (SPC-A and SPC-B) from the –+N–(CH3)3choline 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 versusSARS-CoV-2 positive patients (p= 1.23 × 10–10) and for SARS-CoV-2 negatives versuspositives (p= 1.60 × 10–9). Thus, plasma SPCtotaland 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.
Details
- Language :
- English
- ISSN :
- 00032700 and 15206882
- Volume :
- 93
- Issue :
- 8
- Database :
- Supplemental Index
- Journal :
- Analytical Chemistry
- Publication Type :
- Periodical
- Accession number :
- ejs55648449
- Full Text :
- https://doi.org/10.1021/acs.analchem.0c04952