#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; RAW_FILE_NAME=ID_25.mzML
SUBJECT_SAMPLE_FACTORS           	C034	ID_26	Time-point:D7 | Treatment:Placebo | Sex:F	Age=42; RAW_FILE_NAME=ID_26.mzML
SUBJECT_SAMPLE_FACTORS           	C123	ID_27	Time-point:D14 | Treatment:MP | Sex:M	Age=65; RAW_FILE_NAME=ID_27.mzML
SUBJECT_SAMPLE_FACTORS           	C040	ID_29	Time-point:D1 | Treatment:Placebo | Sex:M	Age=78; RAW_FILE_NAME=ID_29.mzML
SUBJECT_SAMPLE_FACTORS           	C098	ID_31	Time-point:D11 | Treatment:MP | Sex:M	Age=52; RAW_FILE_NAME=ID_31.mzML
SUBJECT_SAMPLE_FACTORS           	C125	ID_32	Time-point:D1 | Treatment:MP | Sex:F	Age=57; RAW_FILE_NAME=ID_32.mzML
SUBJECT_SAMPLE_FACTORS           	C047	ID_34	Time-point:D11 | Treatment:MP | Sex:F	Age=41; RAW_FILE_NAME=ID_34.mzML
SUBJECT_SAMPLE_FACTORS           	C061	ID_35	Time-point:D7 | Treatment:MP | Sex:M	Age=60; RAW_FILE_NAME=ID_35.mzML
SUBJECT_SAMPLE_FACTORS           	C119	ID_37	Time-point:D1 | Treatment:MP | Sex:M	Age=71; RAW_FILE_NAME=ID_37.mzML
SUBJECT_SAMPLE_FACTORS           	C057	ID_39	Time-point:D5 | Treatment:Placebo | Sex:M	Age=63; RAW_FILE_NAME=ID_39.mzML
SUBJECT_SAMPLE_FACTORS           	C132	ID_40	Time-point:D7 | Treatment:Placebo | Sex:M	Age=79; RAW_FILE_NAME=ID_40.mzML
SUBJECT_SAMPLE_FACTORS           	C074	ID_42	Time-point:D5 | Treatment:Placebo | Sex:F	Age=51; RAW_FILE_NAME=ID_42.mzML
SUBJECT_SAMPLE_FACTORS           	C027	ID_43	Time-point:D5 | Treatment:Placebo | Sex:F	Age=72; RAW_FILE_NAME=ID_43.mzML
SUBJECT_SAMPLE_FACTORS           	C097	ID_45	Time-point:D5 | Treatment:Placebo | Sex:M	Age=51; RAW_FILE_NAME=ID_45.mzML
SUBJECT_SAMPLE_FACTORS           	C115	ID_47	Time-point:D7 | Treatment:Placebo | Sex:M	Age=79; RAW_FILE_NAME=ID_47.mzML
SUBJECT_SAMPLE_FACTORS           	C011	ID_49	Time-point:D1 | Treatment:MP | Sex:M	Age=50; RAW_FILE_NAME=ID_49.mzML
SUBJECT_SAMPLE_FACTORS           	C108	ID_51	Time-point:D14 | Treatment:MP | Sex:M	Age=62; RAW_FILE_NAME=ID_51.mzML
SUBJECT_SAMPLE_FACTORS           	C134	ID_53	Time-point:D7 | Treatment:MP | Sex:M	Age=69; RAW_FILE_NAME=ID_53.mzML
SUBJECT_SAMPLE_FACTORS           	C115	ID_55	Time-point:D5 | Treatment:Placebo | Sex:M	Age=79; RAW_FILE_NAME=ID_55.mzML
SUBJECT_SAMPLE_FACTORS           	C054	ID_56	Time-point:D14 | Treatment:MP | Sex:M	Age=54; RAW_FILE_NAME=ID_56.mzML
SUBJECT_SAMPLE_FACTORS           	C057	ID_58	Time-point:D1 | Treatment:Placebo | Sex:M	Age=63; 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