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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST002845 |
| Study Title | Methylprednisolone therapy induces differential metabolic trajectories in severe COVID-19 patients |
| Study Summary | Corticosteroids 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 Name | Gardinassi |
| First Name | Luiz Gustavo |
| Address | R. 235 s/n - Institute of Tropical Pathology and Public Health - Federal University of Goiás |
| luizgardinassi@ufg.br | |
| Phone | +55 62 3209-6530 |
| Submit Date | 2023-08-30 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-09-15 |
| Release Version | 1 |
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Treatment:
| Treatment ID: | TR002966 |
| Treatment Summary: | The participants were administered with either intravenous sodium succinate MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. As per hospital protocol, all patients meeting acute respiratory distress syndrome criteria also preemptively received intravenous ceftriaxone (1g twice daily for 7 days) plus azithromycin (500 mg once a day for 5 days) or clarithromycin (500 mg twice daily for 7 days), starting on Day 1. At inclusion, adult patients were excluded if they had a history of hypersensitivity to MP, were living with human immunodeficiency virus or AIDS, had a history of chronic use of corticosteroids or immunosuppressive agents, were pregnant or breastfeeding, or had decompensated cirrhosis or chronic renal failure. |
