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.
【저자키워드】 SARS-CoV-2, Biomarkers, metabolism, fatty acids, 【초록키워드】 COVID-19, metabolomics, coronavirus, Pathogenesis, SARS-COV-2 infection, severity, Infection, host response, Therapeutic strategies, Triglyceride, death, plasma, target, Degradation, Phospholipase A2, mechanism, therapeutic targets, Evidence, Lipid, Analysis, Phosphatidylcholine, COVID-19 patient, AUC, therapeutic target, arachidonic acid, tyrosine, acute respiratory syndrome, Activation, free fatty acids, control groups, pathogenesis of COVID-19, potential biomarkers, circulating, key factor, porphyrins, Host, Effect, approach, metabolomic, spread to, addition, the disease, provided, characterized, provide, correlated, 【제목키워드】 response, molecule, Revealed, New,