Integrative Modeling of Plasma Metabolic and Lipoprotein Biomarkers of SARS-CoV-2 Infection in Spanish and Australian COVID-19 Patient Cohorts
| Autor: | Sze-How Bong, Hartmut Schaefer, Torben Kimhofer, Rubén Gil-Redondo, Maider Bizkarguenaga, Oscar Millet, Philipp Nitschke, Jeremy K. Nicholson, Chiara Bruzzone, Julien Wist, José M. Mato, Reika Masuda, Elaine Holmes, Nieves Embade, Drew Hall, Manfred Spraul, Samantha Lodge, Ruey Leng Loo |
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| Rok vydání: | 2021 |
| Předmět: |
Plasma lipoprotein
Coronavirus disease 2019 (COVID-19) SARS-CoV-2 business.industry Lipoproteins medicine.medical_treatment Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Metabolite Australia COVID-19 Physiology General Chemistry Biochemistry In vitro diagnostic chemistry.chemical_compound chemistry Fibrinolysis Cohort Humans Medicine business Biomarkers Lipoprotein |
| Zdroj: | Journal of Proteome Research. 20:4139-4152 |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.1c00458 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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