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

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-...

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Autores principales: Gray, Nicola, Lawler, Nathan G., Zeng, Annie Xu, Ryan, Monique, Bong, Sze How, Boughton, Berin A., Bizkarguenaga, Maider, Bruzzone, Chiara, Embade, Nieves, Wist, Julien, Holmes, Elaine, Millet, Oscar, Nicholson, Jeremy K., Whiley, Luke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306636/
https://www.ncbi.nlm.nih.gov/pubmed/34357361
http://dx.doi.org/10.3390/metabo11070467
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author Gray, Nicola
Lawler, Nathan G.
Zeng, Annie Xu
Ryan, Monique
Bong, Sze How
Boughton, Berin A.
Bizkarguenaga, Maider
Bruzzone, Chiara
Embade, Nieves
Wist, Julien
Holmes, Elaine
Millet, Oscar
Nicholson, Jeremy K.
Whiley, Luke
author_facet Gray, Nicola
Lawler, Nathan G.
Zeng, Annie Xu
Ryan, Monique
Bong, Sze How
Boughton, Berin A.
Bizkarguenaga, Maider
Bruzzone, Chiara
Embade, Nieves
Wist, Julien
Holmes, Elaine
Millet, Oscar
Nicholson, Jeremy K.
Whiley, Luke
author_sort Gray, Nicola
collection PubMed
description 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.
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spelling pubmed-83066362021-07-25 Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection Gray, Nicola Lawler, Nathan G. Zeng, Annie Xu Ryan, Monique Bong, Sze How Boughton, Berin A. Bizkarguenaga, Maider Bruzzone, Chiara Embade, Nieves Wist, Julien Holmes, Elaine Millet, Oscar Nicholson, Jeremy K. Whiley, Luke Metabolites Article 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. MDPI 2021-07-20 /pmc/articles/PMC8306636/ /pubmed/34357361 http://dx.doi.org/10.3390/metabo11070467 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gray, Nicola
Lawler, Nathan G.
Zeng, Annie Xu
Ryan, Monique
Bong, Sze How
Boughton, Berin A.
Bizkarguenaga, Maider
Bruzzone, Chiara
Embade, Nieves
Wist, Julien
Holmes, Elaine
Millet, Oscar
Nicholson, Jeremy K.
Whiley, Luke
Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection
title Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection
title_full Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection
title_fullStr Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection
title_full_unstemmed Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection
title_short Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection
title_sort diagnostic potential of the plasma lipidome in infectious disease: application to acute sars-cov-2 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306636/
https://www.ncbi.nlm.nih.gov/pubmed/34357361
http://dx.doi.org/10.3390/metabo11070467
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