Integrative Modeling of Plasma Metabolic and Lipoprotein Biomarkers of SARS-CoV-2 Infection in Spanish and Australian COVID-19 Patient Cohorts

Abstract

Quantitative plasma lipoprotein and metabolite profiles were measured on an autonomous community of the Basque Country (Spain) cohort consisting of hospitalized COVID-19 patients (<i>n</i> = 72) and a matched control group (<i>n</i> = 75) and a Western Australian (WA) cohort consisting of (<i>n</i> = 17) SARS-CoV-2 positives and (<i>n</i> = 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.