Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV‑2 Infection

The
metabolic effects of severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) infection on human blood plasma were characterized
using multiplatform metabolic phenotyping with nuclear magnetic resonance
(NMR) spectroscopy and liquid chromatography–mass spectrometry
(LC-MS). Quantitative measurements of lipoprotein subfractions, α-1-acid
glycoprotein, glucose, and biogenic amines were made on samples from
symptomatic coronavirus disease 19 (COVID-19) patients who had tested
positive for the SARS-CoV-2 virus (n = 17) and from
age- and gender-matched controls (n = 25). Data were
analyzed using an orthogonal-projections to latent structures (OPLS)
method and used to construct an exceptionally strong (AUROC = 1) hybrid
NMR-MS model that enabled detailed metabolic discrimination between
the groups and their biochemical relationships. Key discriminant metabolites
included markers of inflammation including elevated α-1-acid
glycoprotein and an increased kynurenine/tryptophan ratio. There was
also an abnormal lipoprotein, glucose, and amino acid signature consistent
with diabetes and coronary artery disease (low total and HDL Apolipoprotein
A1, low HDL triglycerides, high LDL and VLDL triglycerides), plus
multiple highly significant amino acid markers of liver dysfunction
(including the elevated glutamine/glutamate and Fischer’s ratios)
that present themselves as part of a distinct SARS-CoV-2 infection
pattern. A multivariate training-test set model was validated using
independent samples from additional SARS-CoV-2 positive patients and
controls. The predictive model showed a sensitivity of 100% for SARS-CoV-2
positivity. The breadth of the disturbed pathways indicates a systemic
signature of SARS-CoV-2 positivity that includes elements of liver
dysfunction, dyslipidemia, diabetes, and coronary heart disease risk
that are consistent with recent reports that COVID-19 is a systemic
disease affecting multiple organs and systems. Metabolights study
reference: MTBLS2014.