期刊
JOURNAL OF PROTEOME RESEARCH
卷 20, 期 8, 页码 4139-4152出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.1c00458
关键词
COVID-19; SARS-CoV-2; NMR spectroscopy; plasma IVDr; metabolic phenotyping; diagnostic modeling; lipoproteins; phenoconversion; population cross-validation
资金
- Department of Industry, Tourism, and Trade of the Government of the Autonomous Community of the Basque Country
- Severo Ochoa Excellence A
- Spinnaker Health Research Foundation, WA.
- McCusker Foundation, WA
- Western Australian State Government
- MRFF
- UK MRC
- Department of Jobs, Tourism, Science, and Innovation, Government of Western Australian Premier's Fellowship
- ARC Laureate Fellowship
This study utilized NMR technology to analyze plasma lipoprotein and metabolite profiles of COVID-19 patients in Spain and Australia, revealing high similarity in lipoproteins but minor differences in metabolites between the two cohorts. Significant infection-related reductions in specific lipoprotein subfractions associated with negative regulation of blood coagulation and fibrinolysis were observed, demonstrating the potential of NMR-based technologies in identifying biomarkers for COVID-19.
Quantitative plasma lipoprotein and metabolite profiles were measured on an autonomous community of the Basque Country (Spain) cohort consisting of hospitalized COVID-19 patients (n = 72) and a matched control group (n = 75) and a Western Australian (WA) cohort consisting of (n = 17) SARS-CoV-2 positives and (n = 20) healthy controls using 600 MHz H-1 nuclear magnetic resonance (NMR) spectroscopy. Spanish samples were measured in two laboratories using one-dimensional (1D) solvent-suppressed and T-2-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.
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