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Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Anal+Chem 2021 ; 93 (8): 3976-3986 Nephropedia Template TP
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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 #MMPMID33577736
Anal Chem 2021[Mar]; 93 (8): 3976-3986 PMID33577736show ga
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 alpha-1-acid glycoprotein and other glycoproteins (designated GlycA and GlycB) that were elevated in SARS-CoV-2 positive patients [p = 2.52 x 10(-10) (GlycA) and 1.25 x 10(-9) (GlycB) vs controls], (b) two diagnostic supramolecular phospholipid composite signals that were identified (SPC-A and SPC-B) from the -(+)N-(CH(3))(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 (SPC(total)) were reduced in SARS-CoV-2 positive patients relative to both controls (p = 1.40 x 10(-7)) and SARS-CoV-2 negative patients (p = 4.52 x 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 SPC(total)/GlycA ratios were also significantly different for control versus SARS-CoV-2 positive patients (p = 1.23 x 10(-10)) and for SARS-CoV-2 negatives versus positives (p = 1.60 x 10(-9)). Thus, plasma SPC(total) and SPC(total)/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.
|Aged[MESH]
|Biomarkers/blood[MESH]
|COVID-19/blood/*diagnosis[MESH]
|Female[MESH]
|Humans[MESH]
|Male[MESH]
|Middle Aged[MESH]
|Multivariate Analysis[MESH]
|Nuclear Magnetic Resonance, Biomolecular/methods[MESH]
|Orosomucoid/*analysis/chemistry[MESH]
|Phospholipids/*blood/chemistry[MESH]
|Proton Magnetic Resonance Spectroscopy/methods/statistics & numerical data[MESH]