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Article

Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2

1
Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
2
Center for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, 28100 Novara, Italy
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Department of Sciences and Technological Innovation, University of Piemonte Orientale, 28100 Alessandria, Italy
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Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy
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Internal and Emergency Medicine Departments, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
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Azienda Ospedaliero-Universitaria “Maggiore della Carità”, 28100 Novara, Italy
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Metabolic Signalling Group, School of Pharmacy & Biomedical Sciences, Curtin University, Perth 6102, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8623; https://doi.org/10.3390/ijms21228623
Received: 21 October 2020 / Revised: 10 November 2020 / Accepted: 12 November 2020 / Published: 16 November 2020
(This article belongs to the Special Issue COVID-19 and Molecular Studies in Biology and Chemistry)
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every continent, registering over 1,250,000 deaths worldwide. The effects of SARS-CoV-2 on host targets remains largely limited, hampering our understanding of Coronavirus Disease 2019 (COVID-19) pathogenesis and the development of therapeutic strategies. The present study used a comprehensive untargeted metabolomic and lipidomic approach to capture the host response to SARS-CoV-2 infection. We found that several circulating lipids acted as potential biomarkers, such as phosphatidylcholine 14:0_22:6 (area under the curve (AUC) = 0.96), phosphatidylcholine 16:1_22:6 (AUC = 0.97), and phosphatidylethanolamine 18:1_20:4 (AUC = 0.94). Furthermore, triglycerides and free fatty acids, especially arachidonic acid (AUC = 0.99) and oleic acid (AUC = 0.98), were well correlated to the severity of the disease. An untargeted analysis of non-critical COVID-19 patients identified a strong alteration of lipids and a perturbation of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, aminoacyl-tRNA degradation, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. The severity of the disease was characterized by the activation of gluconeogenesis and the metabolism of porphyrins, which play a crucial role in the progress of the infection. In addition, our study provided further evidence for considering phospholipase A2 (PLA2) activity as a potential key factor in the pathogenesis of COVID-19 and a possible therapeutic target. To date, the present study provides the largest untargeted metabolomics and lipidomics analysis of plasma from COVID-19 patients and control groups, identifying new mechanisms associated with the host response to COVID-19, potential plasma biomarkers, and therapeutic targets. View Full-Text
Keywords: SARS-CoV-2; biomarkers; metabolism; fatty acids SARS-CoV-2; biomarkers; metabolism; fatty acids
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MDPI and ACS Style

Barberis, E.; Timo, S.; Amede, E.; Vanella, V.V.; Puricelli, C.; Cappellano, G.; Raineri, D.; Cittone, M.G.; Rizzi, E.; Pedrinelli, A.R.; Vassia, V.; Casciaro, F.G.; Priora, S.; Nerici, I.; Galbiati, A.; Hayden, E.; Falasca, M.; Vaschetto, R.; Sainaghi, P.P.; Dianzani, U.; Rolla, R.; Chiocchetti, A.; Baldanzi, G.; Marengo, E.; Manfredi, M. Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2. Int. J. Mol. Sci. 2020, 21, 8623. https://doi.org/10.3390/ijms21228623

AMA Style

Barberis E, Timo S, Amede E, Vanella VV, Puricelli C, Cappellano G, Raineri D, Cittone MG, Rizzi E, Pedrinelli AR, Vassia V, Casciaro FG, Priora S, Nerici I, Galbiati A, Hayden E, Falasca M, Vaschetto R, Sainaghi PP, Dianzani U, Rolla R, Chiocchetti A, Baldanzi G, Marengo E, Manfredi M. Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2. International Journal of Molecular Sciences. 2020; 21(22):8623. https://doi.org/10.3390/ijms21228623

Chicago/Turabian Style

Barberis, Elettra, Sara Timo, Elia Amede, Virginia V. Vanella, Chiara Puricelli, Giuseppe Cappellano, Davide Raineri, Micol G. Cittone, Eleonora Rizzi, Anita R. Pedrinelli, Veronica Vassia, Francesco G. Casciaro, Simona Priora, Ilaria Nerici, Alessandra Galbiati, Eyal Hayden, Marco Falasca, Rosanna Vaschetto, Pier P. Sainaghi, Umberto Dianzani, Roberta Rolla, Annalisa Chiocchetti, Gianluca Baldanzi, Emilio Marengo, and Marcello Manfredi. 2020. "Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2" International Journal of Molecular Sciences 21, no. 22: 8623. https://doi.org/10.3390/ijms21228623

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