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.
Highlights
The novel coronavirus (SARS-CoV-2) led to an outbreak of viral pneumonia in Wuhan, China, which began in December 2019 [1]
Untargeted lipidomics and metabolomics analyses were performed on plasma samples of 161 subjects, 103 of whom were infected with severe acute respiratory syndrome (SARS)-CoV-2
We considered critical patients as those with respiratory failure admitted to the intensive care unit requiring mechanical ventilation (ICU-COVID-19), and non-critical patients as all other patients with mild to severe respiratory failure requiring oxygen supplementation but neither mechanical nor non-invasive ventilation
Summary
The novel coronavirus (SARS-CoV-2) led to an outbreak of viral pneumonia in Wuhan, China, which began in December 2019 [1]. The main organ targeted by SARS-CoV-2 is the low respiratory tract, and some patients develop a life-threatening acute respiratory distress syndrome, acute myocardial injury and chronic damage to the cardiovascular system have been found [5]. Most SARS-CoV-2 studies have focused on its epidemiological and clinical characteristics [6,7]. Recent studies demonstrated that SARS-CoV-2 binds to the angiotensin converting enzyme 2 (ACE2) on the cell surface [8] and that the virus dramatically impacts the immune function [9]. The physiological changes associated with SARS-CoV-2 are not yet clear
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