#METABOLOMICS WORKBENCH gardinassi_20230830_122348 DATATRACK_ID:4268 STUDY_ID:ST002845 ANALYSIS_ID:AN004663 PROJECT_ID:PR001780 VERSION 1 CREATED_ON August 30, 2023, 2:40 pm #PROJECT PR:PROJECT_TITLE Methylprednisolone therapy induces differential metabolic trajectories in severe PR:PROJECT_TITLE COVID-19 patients PR:PROJECT_TYPE Research PR:PROJECT_SUMMARY Corticosteroids have become a choice for managing severe COVID-19, but the PR:PROJECT_SUMMARY molecular mechanisms behind the response after corticosteroid administration PR:PROJECT_SUMMARY remain incompletely understood. In order to unravel this, comparisons between PR:PROJECT_SUMMARY temporal metabolic profiles in the plasma samples of methylprednisolone (MP) - PR:PROJECT_SUMMARY and placebo-treated COVID-19 patients were performed at different time points. PR:PROJECT_SUMMARY The patient plasma samples used were obtained from a double blind, randomized, PR:PROJECT_SUMMARY placebo-controlled Phase IIb clinical trial performed on severe COVID-19 PR:PROJECT_SUMMARY patients in the Brazilian Amazon where the patients received placebo or 0.5 PR:PROJECT_SUMMARY mg/kg MP intravenously twice daily for five days. The MP treatment reduced the PR:PROJECT_SUMMARY number of metabolites in the plasma of patients during follow-up. The PR:PROJECT_SUMMARY longitudinal changes in the MP-group was in eight metabolic pathways related to PR:PROJECT_SUMMARY steroid hormones and eicosanoids. Direct comparison between the two groups, PR:PROJECT_SUMMARY revealed differences at baseline, which peaked five days after initiation of MP PR:PROJECT_SUMMARY treatment. The metabolic pathways differing between the two groups over time PR:PROJECT_SUMMARY included galactose metabolism, glucose and gluconeogenesis, N-glycan metabolism, PR:PROJECT_SUMMARY and prostaglandin formation from arachidonate. Deoxy-galactose, prostaglandin PR:PROJECT_SUMMARY H2, sphingosine, and sphinganine exhibited differential trajectories by day 14 PR:PROJECT_SUMMARY after initiating the MP treatment. Survival of MP-treated COVID-19 patients was PR:PROJECT_SUMMARY associated with modulation of tryptophan metabolism. Network analysis revealed PR:PROJECT_SUMMARY that MP treatment is highly associated with alterations in pathways reflecting PR:PROJECT_SUMMARY eicosanoid metabolism, such as arachidonic acid and prostaglandins. Curiously, PR:PROJECT_SUMMARY there is crosstalk between metabolomics, biochemistry and cytokine components. PR:PROJECT_SUMMARY Treatment of systemic and inflammatory conditions induced by SARS-CoV-2 viral PR:PROJECT_SUMMARY infections with methylprednisolone modulates metabolic activity associated with PR:PROJECT_SUMMARY tryptophan and inflammatory lipids. PR:INSTITUTE Federal University of Goiás PR:LAST_NAME Gardinassi PR:FIRST_NAME Luiz Gustavo PR:ADDRESS R. 235 s/n Institute of Tropical Pathology and Public Health PR:EMAIL luizgardinassi@ufg.br PR:PHONE +55 62 3209-6530 #STUDY ST:STUDY_TITLE Methylprednisolone therapy induces differential metabolic trajectories in severe ST:STUDY_TITLE COVID-19 patients ST:STUDY_SUMMARY Corticosteroids have become a choice for managing severe COVID-19, but the ST:STUDY_SUMMARY molecular mechanisms behind the response after corticosteroid administration ST:STUDY_SUMMARY remain incompletely understood. In order to unravel this, comparisons between ST:STUDY_SUMMARY temporal metabolic profiles in the plasma samples of methylprednisolone (MP) - ST:STUDY_SUMMARY and placebo-treated COVID-19 patients were performed at different time points. ST:STUDY_SUMMARY The patient plasma samples used were obtained from a double blind, randomized, ST:STUDY_SUMMARY placebo-controlled Phase IIb clinical trial performed on severe COVID-19 ST:STUDY_SUMMARY patients in the Brazilian Amazon where the patients received placebo or 0.5 ST:STUDY_SUMMARY mg/kg MP intravenously twice daily for five days. The MP treatment reduced the ST:STUDY_SUMMARY number of metabolites in the plasma of patients during follow-up. The ST:STUDY_SUMMARY longitudinal changes in the MP-group was in eight metabolic pathways related to ST:STUDY_SUMMARY steroid hormones and eicosanoids. Direct comparison between the two groups, ST:STUDY_SUMMARY revealed differences at baseline, which peaked five days after initiation of MP ST:STUDY_SUMMARY treatment. The metabolic pathways differing between the two groups over time ST:STUDY_SUMMARY included galactose metabolism, glucose and gluconeogenesis, N-glycan metabolism, ST:STUDY_SUMMARY and prostaglandin formation from arachidonate. Deoxy-galactose, prostaglandin ST:STUDY_SUMMARY H2, sphingosine, and sphinganine exhibited differential trajectories by day 14 ST:STUDY_SUMMARY after initiating the MP treatment. Survival of MP-treated COVID-19 patients was ST:STUDY_SUMMARY associated with modulation of tryptophan metabolism. Network analysis revealed ST:STUDY_SUMMARY that MP treatment is highly associated with alterations in pathways reflecting ST:STUDY_SUMMARY eicosanoid metabolism, such as arachidonic acid and prostaglandins. Curiously, ST:STUDY_SUMMARY there is crosstalk between metabolomics, biochemistry and cytokine components. ST:STUDY_SUMMARY Treatment of systemic and inflammatory conditions induced by SARS-CoV-2 viral ST:STUDY_SUMMARY infections with methylprednisolone modulates metabolic activity associated with ST:STUDY_SUMMARY tryptophan and inflammatory lipids. ST:INSTITUTE Federal University of Goiás ST:LAST_NAME Gardinassi ST:FIRST_NAME Luiz Gustavo ST:ADDRESS R. 235 s/n - Institute of Tropical Pathology and Public Health - Federal ST:ADDRESS University of Goiás ST:EMAIL luizgardinassi@ufg.br ST:PHONE +55 62 3209-6530 #SUBJECT SU:SUBJECT_TYPE Human SU:SUBJECT_SPECIES Homo sapiens SU:TAXONOMY_ID 9606 SU:GENDER Male and female #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data SUBJECT_SAMPLE_FACTORS C134 ID_1 Time-point:D14 | Treatment:MP | Sex:M Age=69; RAW_FILE_NAME=ID_1.mzML SUBJECT_SAMPLE_FACTORS C118 ID_2 Time-point:D5 | Treatment:Placebo | Sex:M Age=75; RAW_FILE_NAME=ID_2.mzML SUBJECT_SAMPLE_FACTORS C086 ID_3 Time-point:D11 | Treatment:MP | Sex:F Age=55; RAW_FILE_NAME=ID_3.mzML SUBJECT_SAMPLE_FACTORS C027 ID_6 Time-point:D1 | Treatment:Placebo | Sex:F Age=72; RAW_FILE_NAME=ID_6.mzML SUBJECT_SAMPLE_FACTORS C047 ID_7 Time-point:D5 | Treatment:MP | Sex:F Age=41; RAW_FILE_NAME=ID_7.mzML SUBJECT_SAMPLE_FACTORS C100 ID_9 Time-point:D1 | Treatment:Placebo | Sex:M Age=53; RAW_FILE_NAME=ID_9.mzML SUBJECT_SAMPLE_FACTORS C117 ID_11 Time-point:D14 | Treatment:MP | Sex:M Age=23; RAW_FILE_NAME=ID_11.mzML SUBJECT_SAMPLE_FACTORS C108 ID_12 Time-point:D7 | Treatment:MP | Sex:M Age=62; RAW_FILE_NAME=ID_12.mzML SUBJECT_SAMPLE_FACTORS C011 ID_14 Time-point:D11 | Treatment:MP | Sex:M Age=50; RAW_FILE_NAME=ID_14.mzML SUBJECT_SAMPLE_FACTORS C109 ID_16 Time-point:D1 | Treatment:Placebo | Sex:M Age=77; RAW_FILE_NAME=ID_16.mzML SUBJECT_SAMPLE_FACTORS C132 ID_18 Time-point:D5 | Treatment:Placebo | Sex:M Age=79; RAW_FILE_NAME=ID_18.mzML SUBJECT_SAMPLE_FACTORS C059 ID_20 Time-point:D1 | Treatment:MP | Sex:M Age=65; RAW_FILE_NAME=ID_20.mzML SUBJECT_SAMPLE_FACTORS C074 ID_21 Time-point:D11 | Treatment:Placebo | Sex:F Age=51; RAW_FILE_NAME=ID_21.mzML SUBJECT_SAMPLE_FACTORS C123 ID_23 Time-point:D7 | Treatment:MP | Sex:M Age=65; RAW_FILE_NAME=ID_23.mzML SUBJECT_SAMPLE_FACTORS C080 ID_25 Time-point:D1 | Treatment:Placebo | Sex:M Age=62; 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RAW_FILE_NAME=ID_58.mzML SUBJECT_SAMPLE_FACTORS C080 ID_60 Time-point:D7 | Treatment:Placebo | Sex:M Age=62; RAW_FILE_NAME=ID_60.mzML SUBJECT_SAMPLE_FACTORS C054 ID_62 Time-point:D7 | Treatment:MP | Sex:M Age=54; RAW_FILE_NAME=ID_62.mzML SUBJECT_SAMPLE_FACTORS C123 ID_63 Time-point:D11 | Treatment:MP | Sex:M Age=65; RAW_FILE_NAME=ID_63.mzML SUBJECT_SAMPLE_FACTORS C074 ID_66 Time-point:D1 | Treatment:Placebo | Sex:F Age=51; RAW_FILE_NAME=ID_66.mzML SUBJECT_SAMPLE_FACTORS C129 ID_67 Time-point:D11 | Treatment:MP | Sex:F Age=76; RAW_FILE_NAME=ID_67.mzML SUBJECT_SAMPLE_FACTORS C118 ID_69 Time-point:D7 | Treatment:Placebo | Sex:M Age=75; RAW_FILE_NAME=ID_69.mzML SUBJECT_SAMPLE_FACTORS C058 ID_70 Time-point:D5 | Treatment:Placebo | Sex:M Age=60; RAW_FILE_NAME=ID_70.mzML SUBJECT_SAMPLE_FACTORS C011 ID_71 Time-point:D14 | Treatment:MP | Sex:M Age=50; RAW_FILE_NAME=ID_71.mzML SUBJECT_SAMPLE_FACTORS C118 ID_73 Time-point:D1 | Treatment:Placebo | Sex:M Age=75; RAW_FILE_NAME=ID_73.mzML SUBJECT_SAMPLE_FACTORS C034 ID_75 Time-point:D1 | Treatment:Placebo | Sex:F Age=42; RAW_FILE_NAME=ID_75.mzML SUBJECT_SAMPLE_FACTORS C079 ID_77 Time-point:D14 | Treatment:Placebo | Sex:F Age=52; RAW_FILE_NAME=ID_77.mzML SUBJECT_SAMPLE_FACTORS C118 ID_78 Time-point:D11 | Treatment:Placebo | Sex:M Age=75; RAW_FILE_NAME=ID_78.mzML SUBJECT_SAMPLE_FACTORS C101 ID_80 Time-point:D11 | Treatment:MP | Sex:M Age=77; RAW_FILE_NAME=ID_80.mzML SUBJECT_SAMPLE_FACTORS C033 ID_81 Time-point:D5 | Treatment:MP | Sex:M Age=69; RAW_FILE_NAME=ID_81.mzML SUBJECT_SAMPLE_FACTORS C097 ID_83 Time-point:D1 | Treatment:Placebo | Sex:M Age=51; RAW_FILE_NAME=ID_83.mzML SUBJECT_SAMPLE_FACTORS C117 ID_85 Time-point:D1 | Treatment:MP | Sex:M Age=23; RAW_FILE_NAME=ID_85.mzML SUBJECT_SAMPLE_FACTORS C059 ID_86 Time-point:D14 | Treatment:MP | Sex:M Age=65; RAW_FILE_NAME=ID_86.mzML SUBJECT_SAMPLE_FACTORS C086 ID_88 Time-point:D5 | Treatment:MP | Sex:F Age=55; RAW_FILE_NAME=ID_88.mzML SUBJECT_SAMPLE_FACTORS C054 ID_90 Time-point:D1 | Treatment:MP | Sex:M Age=54; RAW_FILE_NAME=ID_90.mzML SUBJECT_SAMPLE_FACTORS C115 ID_91 Time-point:D11 | Treatment:Placebo | Sex:M Age=79; RAW_FILE_NAME=ID_91.mzML SUBJECT_SAMPLE_FACTORS C101 ID_93 Time-point:D5 | Treatment:MP | Sex:M Age=77; RAW_FILE_NAME=ID_93.mzML SUBJECT_SAMPLE_FACTORS C132 ID_94 Time-point:D1 | Treatment:Placebo | Sex:M Age=79; RAW_FILE_NAME=ID_94.mzML SUBJECT_SAMPLE_FACTORS C097 ID_96 Time-point:D14 | Treatment:Placebo | Sex:M Age=51; RAW_FILE_NAME=ID_96.mzML SUBJECT_SAMPLE_FACTORS C098 ID_98 Time-point:D5 | Treatment:MP | Sex:M Age=52; RAW_FILE_NAME=ID_98.mzML SUBJECT_SAMPLE_FACTORS C119 ID_99 Time-point:D11 | Treatment:MP | Sex:M Age=71; RAW_FILE_NAME=ID_99.mzML SUBJECT_SAMPLE_FACTORS C061 ID_100 Time-point:D5 | Treatment:MP | Sex:M Age=60; RAW_FILE_NAME=ID_100.mzML SUBJECT_SAMPLE_FACTORS C134 ID_101 Time-point:D1 | Treatment:MP | Sex:M Age=69; RAW_FILE_NAME=ID_101.mzML SUBJECT_SAMPLE_FACTORS C058 ID_103 Time-point:D7 | Treatment:Placebo | Sex:M Age=60; RAW_FILE_NAME=ID_103.mzML SUBJECT_SAMPLE_FACTORS C100 ID_104 Time-point:D7 | Treatment:Placebo | Sex:M Age=53; RAW_FILE_NAME=ID_104.mzML SUBJECT_SAMPLE_FACTORS C011 ID_105 Time-point:D7 | Treatment:MP | Sex:M Age=50; RAW_FILE_NAME=ID_105.mzML SUBJECT_SAMPLE_FACTORS C061 ID_107 Time-point:D1 | Treatment:MP | Sex:M Age=60; RAW_FILE_NAME=ID_107.mzML SUBJECT_SAMPLE_FACTORS C132 ID_108 Time-point:D11 | Treatment:Placebo | Sex:M Age=79; RAW_FILE_NAME=ID_108.mzML SUBJECT_SAMPLE_FACTORS C086 ID_110 Time-point:D1 | Treatment:MP | Sex:F Age=55; RAW_FILE_NAME=ID_110.mzML SUBJECT_SAMPLE_FACTORS C123 ID_111 Time-point:D5 | Treatment:MP | Sex:M Age=65; RAW_FILE_NAME=ID_111.mzML SUBJECT_SAMPLE_FACTORS C059 ID_113 Time-point:D11 | Treatment:MP | Sex:M Age=65; RAW_FILE_NAME=ID_113.mzML SUBJECT_SAMPLE_FACTORS C129 ID_115 Time-point:D5 | Treatment:MP | Sex:F Age=76; RAW_FILE_NAME=ID_115.mzML SUBJECT_SAMPLE_FACTORS C108 ID_116 Time-point:D11 | Treatment:MP | Sex:M Age=62; RAW_FILE_NAME=ID_116.mzML SUBJECT_SAMPLE_FACTORS C134 ID_118 Time-point:D11 | Treatment:MP | Sex:M Age=69; RAW_FILE_NAME=ID_118.mzML SUBJECT_SAMPLE_FACTORS C011 ID_119 Time-point:D5 | Treatment:MP | Sex:M Age=50; RAW_FILE_NAME=ID_119.mzML SUBJECT_SAMPLE_FACTORS C040 ID_121 Time-point:D5 | Treatment:Placebo | Sex:M Age=78; RAW_FILE_NAME=ID_121.mzML SUBJECT_SAMPLE_FACTORS C059 ID_123 Time-point:D5 | Treatment:MP | Sex:M Age=65; RAW_FILE_NAME=ID_123.mzML SUBJECT_SAMPLE_FACTORS C115 ID_124 Time-point:D14 | Treatment:Placebo | Sex:M Age=79; RAW_FILE_NAME=ID_124.mzML SUBJECT_SAMPLE_FACTORS C125 ID_126 Time-point:D7 | Treatment:MP | Sex:F Age=57; RAW_FILE_NAME=ID_126.mzML SUBJECT_SAMPLE_FACTORS C033 ID_127 Time-point:D1 | Treatment:MP | Sex:M Age=69; RAW_FILE_NAME=ID_127.mzML SUBJECT_SAMPLE_FACTORS C059 ID_129 Time-point:D7 | Treatment:MP | Sex:M Age=65; RAW_FILE_NAME=ID_129.mzML SUBJECT_SAMPLE_FACTORS C079 ID_131 Time-point:D5 | Treatment:Placebo | Sex:F Age=52; RAW_FILE_NAME=ID_131.mzML SUBJECT_SAMPLE_FACTORS C109 ID_132 Time-point:D14 | Treatment:Placebo | Sex:M Age=77; RAW_FILE_NAME=ID_132.mzML SUBJECT_SAMPLE_FACTORS C117 ID_134 Time-point:D7 | Treatment:MP | Sex:M Age=23; RAW_FILE_NAME=ID_134.mzML SUBJECT_SAMPLE_FACTORS C041 ID_135 Time-point:D1 | Treatment:Placebo | Sex:M Age=67; RAW_FILE_NAME=ID_135.mzML SUBJECT_SAMPLE_FACTORS C079 ID_137 Time-point:D11 | Treatment:Placebo | Sex:F Age=52; RAW_FILE_NAME=ID_137.mzML SUBJECT_SAMPLE_FACTORS C109 ID_138 Time-point:D7 | Treatment:Placebo | Sex:M Age=77; RAW_FILE_NAME=ID_138.mzML SUBJECT_SAMPLE_FACTORS C058 ID_139 Time-point:D1 | Treatment:Placebo | Sex:M Age=60; RAW_FILE_NAME=ID_139.mzML SUBJECT_SAMPLE_FACTORS C061 ID_141 Time-point:D14 | Treatment:MP | Sex:M Age=60; RAW_FILE_NAME=ID_141.mzML SUBJECT_SAMPLE_FACTORS C129 ID_143 Time-point:D7 | Treatment:MP | Sex:F Age=76; RAW_FILE_NAME=ID_143.mzML SUBJECT_SAMPLE_FACTORS C101 ID_145 Time-point:D1 | Treatment:MP | Sex:M Age=77; RAW_FILE_NAME=ID_145.mzML SUBJECT_SAMPLE_FACTORS C129 ID_146 Time-point:D14 | Treatment:MP | Sex:F Age=76; RAW_FILE_NAME=ID_146.mzML SUBJECT_SAMPLE_FACTORS C079 ID_148 Time-point:D1 | Treatment:Placebo | Sex:F Age=52; RAW_FILE_NAME=ID_148.mzML SUBJECT_SAMPLE_FACTORS C098 ID_150 Time-point:D7 | Treatment:MP | Sex:M Age=52; RAW_FILE_NAME=ID_150.mzML SUBJECT_SAMPLE_FACTORS C108 ID_151 Time-point:D1 | Treatment:MP | Sex:M Age=62; RAW_FILE_NAME=ID_151.mzML SUBJECT_SAMPLE_FACTORS C034 ID_153 Time-point:D5 | Treatment:Placebo | Sex:F Age=42; RAW_FILE_NAME=ID_153.mzML SUBJECT_SAMPLE_FACTORS C098 ID_155 Time-point:D1 | Treatment:MP | Sex:M Age=52; RAW_FILE_NAME=ID_155.mzML SUBJECT_SAMPLE_FACTORS C100 ID_156 Time-point:D14 | Treatment:Placebo | Sex:M Age=53; RAW_FILE_NAME=ID_156.mzML SUBJECT_SAMPLE_FACTORS C119 ID_158 Time-point:D7 | Treatment:MP | Sex:M Age=71; RAW_FILE_NAME=ID_158.mzML SUBJECT_SAMPLE_FACTORS C061 ID_159 Time-point:D11 | Treatment:MP | Sex:M Age=60; RAW_FILE_NAME=ID_159.mzML SUBJECT_SAMPLE_FACTORS C115 ID_161 Time-point:D1 | Treatment:Placebo | Sex:M Age=79; RAW_FILE_NAME=ID_161.mzML SUBJECT_SAMPLE_FACTORS C134 ID_163 Time-point:D5 | Treatment:MP | Sex:M Age=69; RAW_FILE_NAME=ID_163.mzML SUBJECT_SAMPLE_FACTORS C047 ID_165 Time-point:D14 | Treatment:MP | Sex:F Age=41; RAW_FILE_NAME=ID_165.mzML SUBJECT_SAMPLE_FACTORS C100 ID_166 Time-point:D5 | Treatment:Placebo | Sex:M Age=53; RAW_FILE_NAME=ID_166.mzML SUBJECT_SAMPLE_FACTORS C074 ID_167 Time-point:D14 | Treatment:Placebo | Sex:F Age=51; RAW_FILE_NAME=ID_167.mzML SUBJECT_SAMPLE_FACTORS C125 ID_169 Time-point:D5 | Treatment:MP | Sex:F Age=57; RAW_FILE_NAME=ID_169.mzML SUBJECT_SAMPLE_FACTORS C129 ID_172 Time-point:D1 | Treatment:MP | Sex:F Age=76; RAW_FILE_NAME=ID_172.mzML SUBJECT_SAMPLE_FACTORS C080 ID_173 Time-point:D11 | Treatment:Placebo | Sex:M Age=62; RAW_FILE_NAME=ID_173.mzML SUBJECT_SAMPLE_FACTORS C108 ID_174 Time-point:D5 | Treatment:MP | Sex:M Age=62; RAW_FILE_NAME=ID_174.mzML SUBJECT_SAMPLE_FACTORS C123 ID_176 Time-point:D1 | Treatment:MP | Sex:M Age=65; RAW_FILE_NAME=ID_176.mzML SUBJECT_SAMPLE_FACTORS C132 ID_177 Time-point:D14 | Treatment:Placebo | Sex:M Age=79; RAW_FILE_NAME=ID_177.mzML SUBJECT_SAMPLE_FACTORS C109 ID_179 Time-point:D5 | Treatment:Placebo | Sex:M Age=77; RAW_FILE_NAME=ID_179.mzML SUBJECT_SAMPLE_FACTORS C097 ID_180 Time-point:D11 | Treatment:Placebo | Sex:M Age=51; RAW_FILE_NAME=ID_180.mzML SUBJECT_SAMPLE_FACTORS C047 ID_181 Time-point:D1 | Treatment:MP | Sex:F Age=41; RAW_FILE_NAME=ID_181.mzML SUBJECT_SAMPLE_FACTORS C054 ID_183 Time-point:D5 | Treatment:MP | Sex:M Age=54; RAW_FILE_NAME=ID_183.mzML SUBJECT_SAMPLE_FACTORS C080 ID_185 Time-point:D5 | Treatment:Placebo | Sex:M Age=62; RAW_FILE_NAME=ID_185.mzML SUBJECT_SAMPLE_FACTORS C097 ID_187 Time-point:D7 | Treatment:Placebo | Sex:M Age=51; RAW_FILE_NAME=ID_187.mzML SUBJECT_SAMPLE_FACTORS C101 ID_188 Time-point:D14 | Treatment:MP | Sex:M Age=77; RAW_FILE_NAME=ID_188.mzML SUBJECT_SAMPLE_FACTORS C041 ID_190 Time-point:D5 | Treatment:Placebo | Sex:M Age=67; RAW_FILE_NAME=ID_190.mzML SUBJECT_SAMPLE_FACTORS C119 ID_191 Time-point:D14 | Treatment:MP | Sex:M Age=71; RAW_FILE_NAME=ID_191.mzML SUBJECT_SAMPLE_FACTORS C047 ID_193 Time-point:D7 | Treatment:MP | Sex:F Age=41; RAW_FILE_NAME=ID_193.mzML SUBJECT_SAMPLE_FACTORS C119 ID_194 Time-point:D5 | Treatment:MP | Sex:M Age=71; RAW_FILE_NAME=ID_194.mzML SUBJECT_SAMPLE_FACTORS C074 ID_196 Time-point:D7 | Treatment:Placebo | Sex:F Age=51; RAW_FILE_NAME=ID_196.mzML SUBJECT_SAMPLE_FACTORS C117 ID_198 Time-point:D11 | Treatment:MP | Sex:M Age=23; RAW_FILE_NAME=ID_198.mzML SUBJECT_SAMPLE_FACTORS C079 ID_199 Time-point:D7 | Treatment:Placebo | Sex:F Age=52; RAW_FILE_NAME=ID_199.mzML SUBJECT_SAMPLE_FACTORS C054 ID_201 Time-point:D11 | Treatment:MP | Sex:M Age=54; RAW_FILE_NAME=ID_201.mzML SUBJECT_SAMPLE_FACTORS C101 ID_202 Time-point:D7 | Treatment:MP | Sex:M Age=77; RAW_FILE_NAME=ID_202.mzML SUBJECT_SAMPLE_FACTORS C100 ID_204 Time-point:D11 | Treatment:Placebo | Sex:M Age=53; RAW_FILE_NAME=ID_204.mzML SUBJECT_SAMPLE_FACTORS C086 ID_206 Time-point:D7 | Treatment:MP | Sex:F Age=55; RAW_FILE_NAME=ID_206.mzML SUBJECT_SAMPLE_FACTORS C109 ID_208 Time-point:D11 | Treatment:Placebo | Sex:M Age=77; RAW_FILE_NAME=ID_208.mzML SUBJECT_SAMPLE_FACTORS C117 ID_209 Time-point:D5 | Treatment:MP | Sex:M Age=23; RAW_FILE_NAME=ID_209.mzML #COLLECTION CO:COLLECTION_SUMMARY The COVID-19 infected participants in this study were drawn from the MetCOVID CO:COLLECTION_SUMMARY study, a parallel, double blind, randomized, placebo-controlled Phase IIb CO:COLLECTION_SUMMARY clinical trial, that assessed the efficacy of MP in treating hospitalized CO:COLLECTION_SUMMARY patients with suspected SARS-CoV-2 infection. Individuals with COVID-19 were CO:COLLECTION_SUMMARY admitted at the Hospital e Pronto-Socorro Delphina Rinaldi Abdel Aziz, in CO:COLLECTION_SUMMARY Manaus, Western Brazilian Amazon. The hospital was the largest public reference CO:COLLECTION_SUMMARY unit for the treatment of severe COVID-19 cases in the city. After confirmation CO:COLLECTION_SUMMARY of SARS-CoV-2 infection by RT-qPCR testing of nasopharyngeal swabs, blood was CO:COLLECTION_SUMMARY collected from patients and the separated plasma was stored at -80oC. The plasma CO:COLLECTION_SUMMARY samples were collected at the day of inclusion (D1) before treatment, and day CO:COLLECTION_SUMMARY five (D5), day seven (D7), day eleven (D11), and day fourteen (D14) after the CO:COLLECTION_SUMMARY start of treatment for metabolomic analysis. CO:SAMPLE_TYPE Blood (plasma) #TREATMENT TR:TREATMENT_SUMMARY The participants were administered with either intravenous sodium succinate MP TR:TREATMENT_SUMMARY (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. As per hospital TR:TREATMENT_SUMMARY protocol, all patients meeting acute respiratory distress syndrome criteria also TR:TREATMENT_SUMMARY preemptively received intravenous ceftriaxone (1g twice daily for 7 days) plus TR:TREATMENT_SUMMARY azithromycin (500 mg once a day for 5 days) or clarithromycin (500 mg twice TR:TREATMENT_SUMMARY daily for 7 days), starting on Day 1. At inclusion, adult patients were excluded TR:TREATMENT_SUMMARY if they had a history of hypersensitivity to MP, were living with human TR:TREATMENT_SUMMARY immunodeficiency virus or AIDS, had a history of chronic use of corticosteroids TR:TREATMENT_SUMMARY or immunosuppressive agents, were pregnant or breastfeeding, or had TR:TREATMENT_SUMMARY decompensated cirrhosis or chronic renal failure. #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Metabolites were extracted from plasma samples using acetonitrile (2:1, v/v). SP:SAMPLEPREP_SUMMARY Stable isotopes caffeine-¹³C3 and progesterone-d9 were used as internal SP:SAMPLEPREP_SUMMARY standards. #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY The binary mobile phases were water 0.5% formic acid with 5 mM of ammonium CH:CHROMATOGRAPHY_SUMMARY formate (A), and acetonitrile (B). Their gradient elution started with 20% (B) CH:CHROMATOGRAPHY_SUMMARY for 5 min, then linearly increased to 100% (B) in 30 min and kept constant for 8 CH:CHROMATOGRAPHY_SUMMARY min in 100% (B). The eluent was restored to the initial conditions in 4 minutes CH:CHROMATOGRAPHY_SUMMARY to re-equilibrate the column and held for the remaining 8 minutes. The flow rate CH:CHROMATOGRAPHY_SUMMARY was kept at 0.5 mL min-1. The injection volume for analysis was 3 μL, and the CH:CHROMATOGRAPHY_SUMMARY column temperature was set at 35 °C. CH:CHROMATOGRAPHY_TYPE Reversed phase CH:INSTRUMENT_NAME Agilent 1220 Infinity CH:COLUMN_NAME Agilent Zorbax Eclipse Plus C18 (150 x 4.6mm,3.5um) CH:SOLVENT_A 100% water; 0.5% formic acid; 5 mM of ammonium formate CH:SOLVENT_B 100% acetonitrile CH:FLOW_GRADIENT gradient elution started with 20% (B) for 5 min, then linearly increased to 100% CH:FLOW_GRADIENT (B) in 30 min and kept constant for 8 min in 100% (B). The eluent was restored CH:FLOW_GRADIENT to the initial conditions in 4 minutes to re-equilibrate the column and held for CH:FLOW_GRADIENT the remaining 8 minutes. CH:FLOW_RATE 0.5 mL/min CH:COLUMN_TEMPERATURE 35 #ANALYSIS AN:ANALYSIS_TYPE MS #MS MS:INSTRUMENT_NAME Thermo Q Exactive Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:ION_MODE POSITIVE MS:MS_COMMENTS The electrospray ionization was operating with the following settings: spray MS:MS_COMMENTS voltage 3.5 kV; capillary temperature: 269 °C; S-lens RF level 50 V; sheath gas MS:MS_COMMENTS flow rate at 53 L min-1; aux gas flow rate at 14 L min-1; sweep gas flow rate 3 MS:MS_COMMENTS L min-1. The high-resolution mass-spectrometry was obtained under full MS/dd-MS2 MS:MS_COMMENTS mode. The mass range in the full MS scanning experiments was m/z 80-1200. The MS:MS_COMMENTS max IT was set at 200 ms, and AGC target was set at 1 x 106. For fragmentation MS:MS_COMMENTS acquisition, the top 5 (TopN, 5, loop count 5) most abundant precursors were MS:MS_COMMENTS sequentially transferred into the C-Trap (AGC target 1 x 105; max IT 50 ms) for MS:MS_COMMENTS collision. The collision energy for target analytes was 20, 30 and 35 eV. MS:MS_COMMENTS Resolving power was set at 140,000 and 70,000 for full MS and dd-MS2 MS:MS_COMMENTS acquisitions, respectively. MS:MS_RESULTS_FILE ST002845_AN004663_Results.txt UNITS:intesity Has m/z:Yes Has RT:Yes RT units:Minutes #END