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Article

Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection

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Australian National Phenome Centre, Health Futures Institute, Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
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Centre for Computational and Systems Medicine, Health Futures Institute, Harry Perkins Institute, Murdoch University, 5 Robin Warren Drive, Perth, WA 6150, Australia
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Centro de Investigación Cooperativa en Biociencias—CIC bioGUNE, Precision Medicine and Metabolism Laboratory, Basque Research and Technology Alliance, Bizkaia Science and Technology Park, Building 800, 48160 Derio, Spain
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Chemistry Department, Universidad del Valle, Cali 76001, Colombia
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Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK
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Institute of Global Health Innovation, Faculty Building South Kensington Campus, Imperial College London, London SW7 2AZ, UK
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Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia
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Authors to whom correspondence should be addressed.
Academic Editor: Harald C. Köfeler
Metabolites 2021, 11(7), 467; https://doi.org/10.3390/metabo11070467
Received: 10 June 2021 / Revised: 9 July 2021 / Accepted: 12 July 2021 / Published: 20 July 2021
(This article belongs to the Special Issue Lipidomics: Insights into Lipid Metabolism and OMICS Research)
Improved methods are required for investigating the systemic metabolic effects of SARS-CoV-2 infection and patient stratification for precision treatment. We aimed to develop an effective method using lipid profiles for discriminating between SARS-CoV-2 infection, healthy controls, and non-SARS-CoV-2 respiratory infections. Targeted liquid chromatography–mass spectrometry lipid profiling was performed on discovery (20 SARS-CoV-2-positive; 37 healthy controls; 22 COVID-19 symptoms but SARS-CoV-2negative) and validation (312 SARS-CoV-2-positive; 100 healthy controls) cohorts. Orthogonal projection to latent structure-discriminant analysis (OPLS-DA) and Kruskal–Wallis tests were applied to establish discriminant lipids, significance, and effect size, followed by logistic regression to evaluate classification performance. OPLS-DA reported separation of SARS-CoV-2 infection from healthy controls in the discovery cohort, with an area under the curve (AUC) of 1.000. A refined panel of discriminant features consisted of six lipids from different subclasses (PE, PC, LPC, HCER, CER, and DCER). Logistic regression in the discovery cohort returned a training ROC AUC of 1.000 (sensitivity = 1.000, specificity = 1.000) and a test ROC AUC of 1.000. The validation cohort produced a training ROC AUC of 0.977 (sensitivity = 0.855, specificity = 0.948) and a test ROC AUC of 0.978 (sensitivity = 0.948, specificity = 0.922). The lipid panel was also able to differentiate SARS-CoV-2-positive individuals from SARS-CoV-2-negative individuals with COVID-19-like symptoms (specificity = 0.818). Lipid profiling and multivariate modelling revealed a signature offering mechanistic insights into SARS-CoV-2, with strong predictive power, and the potential to facilitate effective diagnosis and clinical management. View Full-Text
Keywords: metabolic phenotyping; infectious disease; lipids; lipidomics; liquid chromatography-mass spectrometry (LC-MS); SARS-CoV-2; COVID-19 metabolic phenotyping; infectious disease; lipids; lipidomics; liquid chromatography-mass spectrometry (LC-MS); SARS-CoV-2; COVID-19
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MDPI and ACS Style

Gray, N.; Lawler, N.G.; Zeng, A.X.; Ryan, M.; Bong, S.H.; Boughton, B.A.; Bizkarguenaga, M.; Bruzzone, C.; Embade, N.; Wist, J.; Holmes, E.; Millet, O.; Nicholson, J.K.; Whiley, L. Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection. Metabolites 2021, 11, 467. https://doi.org/10.3390/metabo11070467

AMA Style

Gray N, Lawler NG, Zeng AX, Ryan M, Bong SH, Boughton BA, Bizkarguenaga M, Bruzzone C, Embade N, Wist J, Holmes E, Millet O, Nicholson JK, Whiley L. Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection. Metabolites. 2021; 11(7):467. https://doi.org/10.3390/metabo11070467

Chicago/Turabian Style

Gray, Nicola, Nathan G. Lawler, Annie X. Zeng, Monique Ryan, Sze H. Bong, Berin A. Boughton, Maider Bizkarguenaga, Chiara Bruzzone, Nieves Embade, Julien Wist, Elaine Holmes, Oscar Millet, Jeremy K. Nicholson, and Luke Whiley. 2021. "Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection" Metabolites 11, no. 7: 467. https://doi.org/10.3390/metabo11070467

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