Asymptomatic infection is a big challenge in curbing the spread of COVID-19. However, its identification and pathogenesis elucidation remain issues. Here, by performing comprehensive lipidomic characterization of serum samples from 89 asymptomatic COVID-19 patients and 178 healthy controls, we screened out a panel of 15 key lipids that could accurately identify asymptomatic patients using a new ensemble learning model based on stacking strategy with a voting algorithm. This strategy provided a high accuracy of 96.0% with only 3.6% false positive rate and 4.8% false negative rate. More importantly, the unique lipid metabolic dysregulation was revealed, especially the enhanced synthesis of membrane phospholipids, altered sphingolipids homeostasis, and differential fatty acids metabolic pattern, implicated the specific host immune, inflammatory, and antiviral responses in asymptomatic COVID-19. This study provides a potential pre-diagnostic method for asymptomatic COVID-19 and molecular clues for the pathogenesis and therapy of this disease.
The biological functions of lipids largely depend on their chemical structures. The position and configuration of C=C bonds are two of the essential attributes that determine the structures of unsaturated lipids. However, simultaneous identification of both attributes remains challenging. Here, we develop a bifunctional visible-light-activated photocycloaddition-photoisomerization reaction system, which enables the dual-resolving of the positional and geometric isomerism of C=C bonds in lipids when combines with liquid chromatography-mass spectrometry. The dual-pathway reaction mechanism is demonstrated by experiments and density functional theory calculations. Based on this bifunctional reaction system, a workflow of deep structural lipidomics is established, and allows the revealing of unique patterns of cis-trans-isomers in bacteria, as well as the tracking of C=C positional isomers changes in mouse brain ischemia. This study not only offers a powerful tool for deep lipid structural biology, but also provides a paradigm for developing the multifunctional visible-light-induced reaction.
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