tetano
Editor, Senior Moderator
Int J Mol Sci
. 2020 Nov 16;21(22):E8623.
doi: 10.3390/ijms21228623.
Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2
Elettra Barberis[SUP] 1 2 [/SUP], Sara Timo[SUP] 2 3 [/SUP], Elia Amede[SUP] 1 2 [/SUP], Virginia V Vanella[SUP] 1 2 [/SUP], Chiara Puricelli[SUP] 4 [/SUP], Giuseppe Cappellano[SUP] 2 4 [/SUP], Davide Raineri[SUP] 2 4 [/SUP], Micol G Cittone[SUP] 5 6 [/SUP], Eleonora Rizzi[SUP] 5 6 [/SUP], Anita R Pedrinelli[SUP] 5 6 [/SUP], Veronica Vassia[SUP] 5 6 [/SUP], Francesco G Casciaro[SUP] 5 6 [/SUP], Simona Priora[SUP] 5 6 [/SUP], Ilaria Nerici[SUP] 5 6 [/SUP], Alessandra Galbiati[SUP] 5 6 [/SUP], Eyal Hayden[SUP] 5 6 [/SUP], Marco Falasca[SUP] 7 [/SUP], Rosanna Vaschetto[SUP] 1 [/SUP], Pier Paolo Sainaghi[SUP] 5 6 [/SUP], Umberto Dianzani[SUP] 4 [/SUP], Roberta Rolla[SUP] 4 [/SUP], Annalisa Chiocchetti[SUP] 2 4 [/SUP], Gianluca Baldanzi[SUP] 1 2 [/SUP], Emilio Marengo[SUP] 2 3 [/SUP], Marcello Manfredi[SUP] 1 2 [/SUP]
Affiliations
Abstract
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.
Keywords: SARS-CoV-2; biomarkers; fatty acids; metabolism.
. 2020 Nov 16;21(22):E8623.
doi: 10.3390/ijms21228623.
Large-Scale Plasma Analysis Revealed New Mechanisms and Molecules Associated with the Host Response to SARS-CoV-2
Elettra Barberis[SUP] 1 2 [/SUP], Sara Timo[SUP] 2 3 [/SUP], Elia Amede[SUP] 1 2 [/SUP], Virginia V Vanella[SUP] 1 2 [/SUP], Chiara Puricelli[SUP] 4 [/SUP], Giuseppe Cappellano[SUP] 2 4 [/SUP], Davide Raineri[SUP] 2 4 [/SUP], Micol G Cittone[SUP] 5 6 [/SUP], Eleonora Rizzi[SUP] 5 6 [/SUP], Anita R Pedrinelli[SUP] 5 6 [/SUP], Veronica Vassia[SUP] 5 6 [/SUP], Francesco G Casciaro[SUP] 5 6 [/SUP], Simona Priora[SUP] 5 6 [/SUP], Ilaria Nerici[SUP] 5 6 [/SUP], Alessandra Galbiati[SUP] 5 6 [/SUP], Eyal Hayden[SUP] 5 6 [/SUP], Marco Falasca[SUP] 7 [/SUP], Rosanna Vaschetto[SUP] 1 [/SUP], Pier Paolo Sainaghi[SUP] 5 6 [/SUP], Umberto Dianzani[SUP] 4 [/SUP], Roberta Rolla[SUP] 4 [/SUP], Annalisa Chiocchetti[SUP] 2 4 [/SUP], Gianluca Baldanzi[SUP] 1 2 [/SUP], Emilio Marengo[SUP] 2 3 [/SUP], Marcello Manfredi[SUP] 1 2 [/SUP]
Affiliations
- PMID: 33207699
- DOI: 10.3390/ijms21228623
Abstract
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.
Keywords: SARS-CoV-2; biomarkers; fatty acids; metabolism.