Summary of Study ST002845

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001780. The data can be accessed directly via it's Project DOI: 10.21228/M8MT5N This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002845
Study TitleMethylprednisolone therapy induces differential metabolic trajectories in severe COVID-19 patients
Study SummaryCorticosteroids have become a choice for managing severe COVID-19, but the molecular mechanisms behind the response after corticosteroid administration remain incompletely understood. In order to unravel this, comparisons between temporal metabolic profiles in the plasma samples of methylprednisolone (MP) - and placebo-treated COVID-19 patients were performed at different time points. The patient plasma samples used were obtained from a double blind, randomized, placebo-controlled Phase IIb clinical trial performed on severe COVID-19 patients in the Brazilian Amazon where the patients received placebo or 0.5 mg/kg MP intravenously twice daily for five days. The MP treatment reduced the number of metabolites in the plasma of patients during follow-up. The longitudinal changes in the MP-group was in eight metabolic pathways related to steroid hormones and eicosanoids. Direct comparison between the two groups, revealed differences at baseline, which peaked five days after initiation of MP treatment. The metabolic pathways differing between the two groups over time included galactose metabolism, glucose and gluconeogenesis, N-glycan metabolism, and prostaglandin formation from arachidonate. Deoxy-galactose, prostaglandin H2, sphingosine, and sphinganine exhibited differential trajectories by day 14 after initiating the MP treatment. Survival of MP-treated COVID-19 patients was associated with modulation of tryptophan metabolism. Network analysis revealed that MP treatment is highly associated with alterations in pathways reflecting eicosanoid metabolism, such as arachidonic acid and prostaglandins. Curiously, there is crosstalk between metabolomics, biochemistry and cytokine components. Treatment of systemic and inflammatory conditions induced by SARS-CoV-2 viral infections with methylprednisolone modulates metabolic activity associated with tryptophan and inflammatory lipids.
Institute
Federal University of Goiás
Last NameGardinassi
First NameLuiz Gustavo
AddressR. 235 s/n - Institute of Tropical Pathology and Public Health - Federal University of Goiás
Emailluizgardinassi@ufg.br
Phone+55 62 3209-6530
Submit Date2023-08-30
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-09-15
Release Version1
Luiz Gustavo Gardinassi Luiz Gustavo Gardinassi
https://dx.doi.org/10.21228/M8MT5N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN004663
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1220 Infinity
Column Agilent Zorbax Eclipse Plus C18 (150 x 4.6mm,3.5um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode POSITIVE
Units intesity

MS:

MS ID:MS004410
Analysis ID:AN004663
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The electrospray ionization was operating with the following settings: spray voltage 3.5 kV; capillary temperature: 269 °C; S-lens RF level 50 V; sheath gas flow rate at 53 L min-1; aux gas flow rate at 14 L min-1; sweep gas flow rate 3 L min-1. The high-resolution mass-spectrometry was obtained under full MS/dd-MS2 mode. The mass range in the full MS scanning experiments was m/z 80-1200. The max IT was set at 200 ms, and AGC target was set at 1 x 106. For fragmentation acquisition, the top 5 (TopN, 5, loop count 5) most abundant precursors were sequentially transferred into the C-Trap (AGC target 1 x 105; max IT 50 ms) for collision. The collision energy for target analytes was 20, 30 and 35 eV. Resolving power was set at 140,000 and 70,000 for full MS and dd-MS2 acquisitions, respectively.
Ion Mode:POSITIVE
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