Machine learning and semi-targeted lipidomics identify distinct serum lipid signatures in hospitalized COVID-19-positive and COVID-19-negative patients

Castañé, Helena; Iftimie, Simona; Baiges-Gayà, Gerard; Rodríguez-Tomàs, Elisabet; Jiménez-Franco, Andrea; López‐Azcona, Ana F.; Garrido, Pedro; Castro, Antoni; Camps, Jordi; Joven, Jorge

doi:10.1016/j.metabol.2022.155197

Cited by 46 publications

(50 citation statements)

References 59 publications

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“…The PE levels increased depending on the severity of the disease. The LPE levels have been reported to be higher 30,32 or lower 17,20 in COVID‐19, depending on the study design. The PE levels have also been reported to be higher in COVID‐19 subjects in some studies, 19,21,26 while the PE levels were lower in others 20,23,25 .…”

Section: Discussionmentioning

confidence: 99%

Dynamic modulations of sphingolipids and glycerophospholipids in COVID‐19

Kurano

Okamoto

Jubishi

et al. 2022

Clinical & Translational Med

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Background A heterogeneous clinical phenotype is a characteristic of coronavirus disease 2019 (COVID‐19). Therefore, investigating biomarkers associated with disease severity is important for understanding the mechanisms responsible for this heterogeneity and for developing novel agents to prevent critical conditions. This study aimed to elucidate the modulations of sphingolipids and glycerophospholipids, which have been shown to possess potent biological properties. Methods We measured the serum sphingolipid and glycerophospholipid levels in a total of 887 samples from 215 COVID‐19 subjects, plus 115 control subjects without infectious diseases and 109 subjects with infectious diseases other than COVID‐19. Results We observed the dynamic modulations of sphingolipids and glycerophospholipids in the serum of COVID‐19 subjects, depending on the time course and severity. The elevation of C16:0 ceramide and lysophosphatidylinositol and decreases in C18:1 ceramide, dihydrosphingosine, lysophosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol were specific to COVID‐19. Regarding the association with maximum severity, phosphatidylinositol and phosphatidylcholine species with long unsaturated acyl chains were negatively associated, while lysophosphatidylethanolamine and phosphatidylethanolamine were positively associated with maximum severity during the early phase. Lysophosphatidylcholine and phosphatidylcholine had strong negative correlations with CRP, while phosphatidylethanolamine had strong positive ones. C16:0 ceramide, lysophosphatidylcholine, phosphatidylcholine and phosphatidylethanolamine species with long unsaturated acyl chains had negative correlations with D‐dimer, while phosphatidylethanolamine species with short acyl chains and phosphatidylinositol had positive ones. Several species of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin might serve as better biomarkers for predicting severe COVID‐19 during the early phase than CRP and D‐dimer. Compared with the lipid modulations seen in mice treated with lipopolysaccharide, tissue factor, or histone, the lipid modulations observed in severe COVID‐19 were most akin to those in mice administered lipopolysaccharide. Conclusion A better understanding of the disturbances in sphingolipids and glycerophospholipids observed in this study will prompt further investigation to develop laboratory testing for predicting maximum severity and/or novel agents to suppress the aggravation of COVID‐19.

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Section: Discussionmentioning

confidence: 99%

Dynamic modulations of sphingolipids and glycerophospholipids in COVID‐19

Kurano

Okamoto

Jubishi

et al. 2022

Clinical & Translational Med

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“…The COVID-19 infection has been associated with alterations in amino acid serum levels, and also with lipids involved in glycerol metabolism, particularly triglycerides [ 10 , 11 , 12 ]. Bile acids have been shown to be dysregulated in COVID-19-positive patients and concentrations have been reported as decreased compared to negative patients [ 13 ]. There are a number of proteomic studies of COVID-19 patients showing some agreement between proteins identified as modulated due to this disease [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment

Spick

Campbell

Baričević-Jones

et al. 2022

IJMS

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Treatments for COVID-19 infections have improved dramatically since the beginning of the pandemic, and glucocorticoids have been a key tool in improving mortality rates. The UK’s National Institute for Health and Care Excellence guidance is for treatment to be targeted only at those requiring oxygen supplementation, however, and the interactions between glucocorticoids and COVID-19 are not completely understood. In this work, a multi-omic analysis of 98 inpatient-recruited participants was performed by quantitative metabolomics (using targeted liquid chromatography-mass spectrometry) and data-independent acquisition proteomics. Both ‘omics datasets were analysed for statistically significant features and pathways differentiating participants whose treatment regimens did or did not include glucocorticoids. Metabolomic differences in glucocorticoid-treated patients included the modulation of cortisol and bile acid concentrations in serum, but no alleviation of serum dyslipidemia or increased amino acid concentrations (including tyrosine and arginine) in the glucocorticoid-treated cohort relative to the untreated cohort. Proteomic pathway analysis indicated neutrophil and platelet degranulation as influenced by glucocorticoid treatment. These results are in keeping with the key role of platelet-associated pathways and neutrophils in COVID-19 pathogenesis and provide opportunity for further understanding of glucocorticoid action. The findings also, however, highlight that glucocorticoids are not fully effective across the wide range of ‘omics dysregulation caused by COVID-19 infections.

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“…The results of pathway enrichment analysis also showed that biosynthesis of unsaturated fatty acids, alpha-linolenic acid metabolism, and arachidonic acid metabolism were significantly changed in serum and lung tissue after QFPDD treatment. In a recent study, fatty acid biosynthesis, arachidonic acid metabolism, and alpha-linolenic acid and linoleic acid metabolism were also found to be altered in COVID-19positive or COVID-19-negative patients compared with healthy controls (Castane et al, 2022). Among the metabolites related to the efficacy of QFPDD, inosine, a nucleotide metabolite, has a significantly positive correlation with inflammatory factors (IL-6 and TNF-a).…”

Section: Discussionmentioning

confidence: 95%

Integrated microbiome and metabolome analysis reveals the potential therapeutic mechanism of Qing-Fei-Pai-Du decoction in mice with coronavirus-induced pneumonia

Zhang

Zheng

et al. 2022

Front. Cell. Infect. Microbiol.

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Current studies have shown that gut microbiota may be closely related to the severity of coronavirus disease 2019 (COVID-19) by regulating the host immune response. Qing-Fei-Pai-Du decoction (QFPDD) is the recommended drug for clinical treatment of patients with COVID-19 in China, but whether it exerts a therapeutic effect by modulating the immune response through gut microbiota remains unclear. In this study, we evaluated the therapeutic effects of QFPDD in pneumonia model mice and performed 16S rRNA sequencing and serum and lung tissue metabolomic analysis to explore the underlying mechanisms during the treatment. Then, Spearman correlation analysis was performed on gut microbiome, serum metabolome, and immune-inflammation-related indicators. Our results suggest that QFPDD can restore the richness and diversity of gut microbiota, and multiple gut microbiota (including Alistipes, Odoribacter, Staphylococcus, Lachnospiraceae_NK4A136_group Enterorhabdus, and unclassified_f_Lachnospiraceae) are significantly associated with immune-inflammation-related indicators. In addition, various types of lipid metabolism changes were observed in serum and lung tissue metabolome, especially glycerophospholipids and fatty acids. A total of 27 differential metabolites (DMs) were significantly correlated with immune-inflammation-related indicators, including 9 glycerophospholipids, 7 fatty acids, 3 linoleic acid, 2 eicosanoids, 2 amino acids, 2 bile acids, and 2 others. Interestingly, these DMs showed a good correlation with the gut microbiota affected by QFPDD. The above results suggest that QFPDD can improve the immune function and reduce inflammation in pneumonia model mice by remodeling gut microbiota and host metabolism.

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Machine learning and semi-targeted lipidomics identify distinct serum lipid signatures in hospitalized COVID-19-positive and COVID-19-negative patients

Cited by 46 publications

References 59 publications

Dynamic modulations of sphingolipids and glycerophospholipids in COVID‐19

Dynamic modulations of sphingolipids and glycerophospholipids in COVID‐19

Multi-Omics Reveals Mechanisms of Partial Modulation of COVID-19 Dysregulation by Glucocorticoid Treatment

Integrated microbiome and metabolome analysis reveals the potential therapeutic mechanism of Qing-Fei-Pai-Du decoction in mice with coronavirus-induced pneumonia

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