Summary of Study ST001849

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 PR001166. The data can be accessed directly via it's Project DOI: 10.21228/M80981 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.

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Study IDST001849
Study TitleLongitudinal Metabolomics of Human Plasma Reveals Robust Prognostic Markers of COVID-19 Disease Severity (part I)
Study SummaryThere is an urgent need to identify which COVID-19 patients will develop life-threatening illness so that medical resources can be optimally allocated and rapid treatment can be administered early in the disease course, when clinical management is most effective. To aid in the prognostic classification of disease severity, we perform untargeted metabolomics on plasma from 339 patients, with samples collected at six longitudinal time points. Using the temporal metabolic profiles and machine learning, we build a predictive model of disease severity. We discover that a panel of metabolites measured at the time of study entry successfully determine disease severity. Through analysis of longitudinal samples, we confirm that the majority of these markers are directly related to disease progression and that their levels are restored to baseline upon disease recovery. Finally, we validate that these metabolites are also altered in a hamster model of COVID-19. Our results indicate that metabolic changes associated with COVID-19 severity can be effectively used to stratify patients and inform resource allocation during the pandemic.
Institute
Washington University in St. Louis
DepartmentChemistry
LaboratoryPatti
Last NamePatti
First NameGary
AddressMcMillen Chemistry Laboratory Washington University 1 Brookings Dr @ Throop Drive Rm 102 St. Louis, MO 63130-4899
Emailgjpattij@wustl.edu
Phone314-935-3512
Submit Date2021-01-29
Num Groups3
Total Subjects339
Num Males184
Num Females155
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2021-06-30
Release Version1
Gary Patti Gary Patti
https://dx.doi.org/10.21228/M80981
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001166
Project DOI:doi: 10.21228/M80981
Project Title:Longitudinal Metabolomics of Human Plasma Reveals Robust Prognostic Markers of COVID-19 Disease Severity
Project Summary:There is an urgent need to identify which COVID-19 patients will develop life-threatening illness so that medical resources can be optimally allocated and rapid treatment can be administered early in the disease course, when clinical management is most effective. To aid in the prognostic classification of disease severity, we perform untargeted metabolomics on plasma from 339 patients, with samples collected at six longitudinal time points. Using the temporal metabolic profiles and machine learning, we build a predictive model of disease severity. We discover that a panel of metabolites measured at the time of study entry successfully determine disease severity. Through analysis of longitudinal samples, we confirm that the majority of these markers are directly related to disease progression and that their levels are restored to baseline upon disease recovery. Finally, we validate that these metabolites are also altered in a hamster model of COVID-19. Our results indicate that metabolic changes associated with COVID-19 severity can be effectively used to stratify patients and inform resource allocation during the pandemic.
Institute:Washington University in St. Louis
Department:Chemistry
Laboratory:Patti
Last Name:Patti
First Name:Gary
Address:McMillen Chemistry Laboratory, Washington University, 1 Brookings Dr @ Throop Drive, Rm 102, St. Louis, MO 63130-4899
Email:gjpattij@wustl.edu
Phone:314-935-3512

Subject:

Subject ID:SU001926
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id batch WU day of presentation SARS-CoV-2 Positive Admitted to the ICU REMDESIVIR on DEXAMETHOSONE on
SA172004B1_WU350-014_d01 d0 Yes Yes - -
SA172005B1_WU350-013_d01 d0 Yes Yes - -
SA172006B1_WU350-029_d01 d0 Yes Yes - -
SA172007B1_WU350-065_d01 d0 Yes Yes - -
SA172008B1_WU350-021_d01 d0 Yes Yes - -
SA172009B1_WU350-041_d01 d0 Yes Yes - -
SA172010B1_WU350-047_d01 d0 Yes Yes - -
SA172011B1_WU350-031_d01 d0 Yes Yes - -
SA172012B1_WU350-050_d01 d0 Yes Yes - -
SA172013B1_WU350-055_d01 d0 Yes Yes - -
SA172014B1_WU350-008_d141 d14 Yes No - -
SA172015B1_WU350-050_d141 d14 Yes Yes - -
SA172016B1_WU350-055_d141 d14 Yes Yes - -
SA172017B1_WU350-009_d141 d14 Yes Yes - -
SA172018B1_WU350-029_d141 d14 Yes Yes - -
SA172019B1_WU350-005_d141 d14 Yes Yes - -
SA172020B1_WU350-065_d141 d14 Yes Yes - -
SA172021B1_WU350-011_d141 d14 Yes Yes - -
SA172022B1_WU350-031_d141 d14 Yes Yes - -
SA172023B1_WU350-041_d141 d14 Yes Yes - -
SA172024B1_WU350-047_d141 d14 Yes Yes - -
SA172025B1_WU350-006_d141 d14 Yes Yes - -
SA172026B1_WU350-021_d141 d14 Yes Yes - -
SA172027B1_WU350-014_d141 d14 Yes Yes - -
SA172028B1_WU350-007_d141 d14 Yes Yes - -
SA172029B1_WU350-013_d141 d14 Yes Yes - -
SA172030B1_WU350-009_d31 d3 Yes Yes - -
SA172031B1_WU350-047_d31 d3 Yes Yes - -
SA172032B1_WU350-065_d31 d3 Yes Yes - -
SA172033B1_WU350-050_d31 d3 Yes Yes - -
SA172034B1_WU350-055_d31 d3 Yes Yes - -
SA172035B1_WU350-014_d31 d3 Yes Yes - -
SA172036B1_WU350-021_d31 d3 Yes Yes - -
SA172037B1_WU350-013_d31 d3 Yes Yes - -
SA172038B1_WU350-011_d31 d3 Yes Yes - -
SA172039B1_WU350-006_d31 d3 Yes Yes - -
SA172040B1_WU350-007_d31 d3 Yes Yes - -
SA172041B1_WU350-029_d31 d3 Yes Yes - -
SA172042B1_WU350-031_d31 d3 Yes Yes - -
SA172043B1_WU350-041_d31 d3 Yes Yes - -
SA172044B1_WU350-041_d71 d7 Yes Yes - -
SA172045B1_WU350-031_d71 d7 Yes Yes - -
SA172046B1_WU350-047_d71 d7 Yes Yes - -
SA172047B1_WU350-021_d71 d7 Yes Yes - -
SA172048B1_WU350-009_d71 d7 Yes Yes - -
SA172049B1_WU350-065_d71 d7 Yes Yes - -
SA172050B1_WU350-055_d71 d7 Yes Yes - -
SA172051B1_WU350-050_d71 d7 Yes Yes - -
SA172052B1_WU350-013_d71 d7 Yes Yes - -
SA172053B1_WU350-004_d71 d7 Yes Yes - -
SA172054B1_WU350-005_d71 d7 Yes Yes - -
SA172055B1_WU350-029_d71 d7 Yes Yes - -
SA172056B1_WU350-006_d71 d7 Yes Yes - -
SA172057B1_WU350-007_d71 d7 Yes Yes - -
SA172058B1_WU350-014_d71 d7 Yes Yes - -
SA172059B1_WU350-011_d71 d7 Yes Yes - -
SA172063B2_WU350-026_d02 d0 No None - -
SA172064B2_WU350-024_d02 d0 No None - -
SA172065B2_WU350-058_d02 d0 No None - -
SA172060B2_WU350-017_d02 d0 No No - -
SA172061B2_WU350-044_d02 d0 No No - -
SA172062B2_WU350-045_d02 d0 No No - -
SA172066B2_WU350-040_d02 d0 No Yes - -
SA172067B2_WU350-020_d02 d0 No Yes - -
SA172068B2_WU350-022_d02 d0 No Yes - -
SA172069B2_WU350-019_d02 d0 No Yes - -
SA172084B2_WU350-063_d02 d0 Yes None - -
SA172085B2_WU350-036_d02 d0 Yes None - -
SA172086B2_WU350-016_d02 d0 Yes None - -
SA172087B2_WU350-035_d02 d0 Yes None - -
SA172070B2_WU350-051_d02 d0 Yes No - -
SA172071B2_WU350-052_d02 d0 Yes No - -
SA172072B2_WU350-057_d02 d0 Yes No - -
SA172073B2_WU350-059_d02 d0 Yes No - -
SA172074B2_WU350-060_d02 d0 Yes No - -
SA172075B2_WU350-061_d02 d0 Yes No - -
SA172076B2_WU350-043_d02 d0 Yes No - -
SA172077B2_WU350-054_d02 d0 Yes No - -
SA172078B2_WU350-032_d02 d0 Yes No - -
SA172079B2_WU350-025_d02 d0 Yes No - -
SA172080B2_WU350-042_d02 d0 Yes No - -
SA172081B2_WU350-030_d02 d0 Yes No - -
SA172082B2_WU350-039_d02 d0 Yes No - -
SA172083B2_WU350-038_d02 d0 Yes No - -
SA172088B2_WU350-084_d02 d0 Yes Yes - -
SA172089B2_WU350-097_d02 d0 Yes Yes - -
SA172090B2_WU350-098_d02 d0 Yes Yes - -
SA172091B2_WU350-062_d02 d0 Yes Yes - -
SA172092B2_WU350-027_d02 d0 Yes Yes - -
SA172093B2_WU350-015_d02 d0 Yes Yes - -
SA172094B2_WU350-028_d02 d0 Yes Yes - -
SA172095B2_WU350-037_d02 d0 Yes Yes - -
SA172096B2_WU350-053_d02 d0 Yes Yes - -
SA172097B2_WU350-048_d02 d0 Yes Yes - -
SA172098B2_WU350-080_d02 d0 Yes Yes - -
SA172099B2_WU350-099_d02 d0 Yes Yes - -
SA172100B2_WU350-023_d02 d0 Yes Yes - -
SA172101B2_WU350-079_d02 d0 Yes Yes - -
SA172102B2_WU350-018_d02 d0 Yes Yes - -
SA172103B2_WU350-079_d142 d14 Yes Yes - -
Showing page 1 of 7     Results:    1  2  3  4  5  Next  Last     Showing results 1 to 100 of 700

Collection:

Collection ID:CO001919
Collection Summary:Over the period of March to August of 2020, blood specimens of 341 individuals who presented at Barnes Jewish Hospital or Christian Hospital located in Saint Louis, Missouri, USA were collected. Inclusion criteria were a physician-ordered SARS-CoV-2 nasopharyngeal swab polymerase chain reaction (PCR) test with a positive or negative outcome, availability of gender and age information, and an age greater than 18. Informed consent was obtained from all study participants. The clinical cohort consisted of 155 female and 186 184 male participants. Out of the 341 339 patients, 274 272 were considered SARS-CoV-2 positive (COV+) and 67 were considered SARS-CoV-2 negative (COV-). Two individuals included in the COV+ group were later determined to be infected with other coronaviruses (NL63, HKu1). Samples were collected at the time of enrollment (d0) to the study, and 3, 7, 14, 28, or 84 days post study entry. Clinically relevant medical information (e.g., patient-reported symptoms, date of symptom-onset, age, race, and BMI) was collected at the time of enrollment from the subject or the medical record. Participant plasma was stored at -80°C upon collection.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR001938
Treatment Summary:This observational study did not evaluate or apply any treatments or therapeutics.

Sample Preparation:

Sampleprep ID:SP001932
Sampleprep Summary:Participant plasma, which had been stored at -80°C upon collection, was thawed on ice. A 50 µL aliquot was transferred onto the solid-phase-extraction (SPE)-system CAPTIVA-EMR Lipid 96-wellplate (Agilent Technologies) before addition of 250 µL of acetonitrile containing 1% formic acid (v/v) and 10 µM internal standard (consisting of uniformly 13C and 15N labeled amino acids from Cambridge Isotope Laboratories, Inc). The samples were mixed for 1 min at 360 rpm on an orbital shaker at room temperature prior to a 10 min incubation period at 4°C. Afterwards, 200 µL 80% acetonitrile in water (v/v) were added to the samples. The samples were mixed on an orbital shaker (360 rpm) for an additional 10 min at room temperature. The samples were then eluted into a 96-deepwell collection plate by centrifugation (10 min, 57 x g, 4°C followed by 2 min, 1000 x g, 4°C). Polar eluates were stored at -80°C until the day of LC/MS analysis. The SPE-plates were then washed twice with 500 µL 80% acetonitrile in water (v/v). Lipids still bound to the SPE-material were then released into a second elution plate, in two elution steps applying 2x 500 µL 1:1 methyl tert-butyl ether:methanol (v/v) onto the SPE cartridge and centrifuging for 2 min at 1000 g and 4°C. The combined eluates were dried under a stream of nitrogen (Biotage SPE Dry Evaporation System) at room temperature and reconstituted with 100 µL 1:1 2-propanol:methanol (v/v) prior to LC/MS analysis.
Processing Storage Conditions:Described in summary
Extract Storage:Described in summary

Combined analysis:

Analysis ID AN002993 AN002994 AN002995 AN002996
Analysis type MS MS MS MS
Chromatography type HILIC HILIC Reversed phase Reversed phase
Chromatography system Agilent 1290 Infinity II Agilent 1290 Infinity II Agilent 1290 Infinity II Agilent 1290 Infinity II
Column SeQuant ZIC-pHILIC (100 x 2.1mm,5um) SeQuant ZIC-pHILIC (100 x 2.1mm,5um) Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um) Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um)
MS Type ESI ESI ESI ESI
MS instrument type QTOF QTOF QTOF QTOF
MS instrument name Agilent 6540 QTOF Agilent 6540 QTOF Agilent 6545 QTOF Agilent 6545 QTOF
Ion Mode POSITIVE NEGATIVE POSITIVE NEGATIVE
Units Relative Intensity Relative Intensity Relative Intensity Relative Intensity

Chromatography:

Chromatography ID:CH002220
Chromatography Summary:An aliquot of 2 µL of polar metabolite extract was subjected to LC/MS analysis by using an Agilent 1290 Infinity II liquid-chromatography (LC) system coupled to an Agilent 6540 Quadrupole-Time-of-Flight (Q-TOF) mass spectrometer with a dual Agilent Jet Stream electrospray ionization source. Polar metabolites were separated on a SeQuant® ZIC®-pHILIC column (100 x 2.1 mm, 5 µm, polymer, Merck-Millipore) including a ZIC®-pHILIC guard column (2.1 mm x 20 mm, 5 µm). The column compartment temperature was maintained at 40°C and the flow rate was set to 250 µL/min. The mobile phases consisted of A: 95% water, 5% acetonitrile, 20 mM ammonium bicarbonate, 0.1% ammonium hydroxide solution (25% ammonia in water), 2.5 µM medronic acid, and B: 95% acetonitrile, 5% water, 2.5 µM medronic acid. The following linear gradient was applied: 0 to 1 min, 90% B; 12 min, 35% B; 12.5 to 14.5 min, 25% B; 15 min, 90% B followed by a re-equilibration phase of 4 min at 400µL/min and 2 min at 250µL/min.
Instrument Name:Agilent 1290 Infinity II
Column Name:SeQuant ZIC-pHILIC (100 x 2.1mm,5um)
Column Temperature:40
Flow Gradient:0 to 1 min, 90% B; 12 min, 35% B; 12.5 to 14.5 min, 25% B; 15 min, 90% B followed by a re-equilibration phase of 4 min
Flow Rate:250ul/min
Solvent A:95% water/5% acetonitrile; 20 mM ammonium bicarbonate; 0.1% ammonium hydroxide; 2.5 µM medronic acid
Solvent B:95% acetonitrile/5% water; 2.5 µM medronic acid
Chromatography Type:HILIC
  
Chromatography ID:CH002221
Chromatography Summary:An aliquot of 2 µL of lipid extract was subjected to LC/MS analysis by using an Agilent 1290 Infinity II LC-system coupled to an Agilent 6545 Q-TOF mass spectrometer with a dual Agilent Jet Stream electrospray ionization source. Lipids were separated on an Acquity UPLC® HSS T3 column (2.1 x 150 mm, 1.8 µm) including an Acquity UPLC® HSS T3 VanGuard Pre-Column (2.1 x 5mm, 1.8 µm) at a temperature of 60°C and a flow rate of 250 µL/min. The mobile phases consisted of A: 60% acetonitrile, 40% water, 0.1% formic acid, 10 mM ammonium formate, 2.5 µM medronic acid, and B: 90% 2-propanol, 10% acetonitrile, 0.1% formic acid, 10 mM ammonium formate (dissolved in 1 mL water). The following linear gradient was used: 0-2 min, 30% B; 17 min, 75% B; 20 min, 85%; 23-26 min, 100% B; 26, 30% B followed by a re-equilibration phase of 5 min.
Instrument Name:Agilent 1290 Infinity II
Column Name:Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um)
Column Temperature:60
Flow Gradient:The following linear gradient was used: 0-2 min, 30% B; 17 min, 75% B; 20 min, 85%; 23-26 min, 100% B; 26, 30% B followed by a re-equilibration phase of 5 min.
Flow Rate:0.25ml/min
Solvent A:60% acetonitrile/40% water; 0.1% formic acid; 10mM ammonium formate; 2.5uM medronic acid
Solvent B:90% isopropanol/10% acetonitrile; 0.1% formic acid; 10 mM ammonium formate
Chromatography Type:Reversed phase

MS:

MS ID:MS002782
Analysis ID:AN002993
Instrument Name:Agilent 6540 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:gas temperature 200°C, drying gas flow 10 L/min, nebulizer pressure 44 psi, sheath gas temperature 300°C, sheath gas flow 12 L/min, VCap 3000 V, nozzle voltage 2000 V, Fragmentor 100 V, Skimmer 65 V, Oct 1 RF Vpp 750 V, and m/z range 50-1700. Data were acquired under continuous reference mass correction at m/z 121.0509 and 922.0890 for positive ion mode and m/z 119.0363 and 966.0007 for negative ion mode. Polar metabolite identifications were supported by matching the retention time, accurate mass, and MS/MS fragmentation data to our in-house retention time and MS/MS library created from authentic reference standards (Mass Spectrometry Metabolite Library supplied by IROA Technologies, Millipore Sigma, St. Louis, MO, USA) and online MS/MS libraries (Human Metabolome Database (HMDB, https://hmdb.ca), Mass Bank of North America (MoNA, https://mona.fiehnlab.ucdavis.edu/), and mzCloud (https://mzcloud.org). Lipid iterative MS/MS data were annotated with the Agilent Lipid Annotator software. All data files were then analyzed in Skyline (Version 20.1.0.155) to obtain peak areas. m/z values of the metabolite and lipid target lists obtained from the metabolite identification workflow, which had at least an MS/MS match to an online library, were extracted under consideration of retention times.
Ion Mode:POSITIVE
  
MS ID:MS002783
Analysis ID:AN002994
Instrument Name:Agilent 6540 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:gas temperature 200°C, drying gas flow 10 L/min, nebulizer pressure 44 psi, sheath gas temperature 300°C, sheath gas flow 12 L/min, VCap 3000 V, nozzle voltage 2000 V, Fragmentor 100 V, Skimmer 65 V, Oct 1 RF Vpp 750 V, and m/z range 50-1700. Data were acquired under continuous reference mass correction at m/z 121.0509 and 922.0890 for positive ion mode and m/z 119.0363 and 966.0007 for negative ion mode. Polar metabolite identifications were supported by matching the retention time, accurate mass, and MS/MS fragmentation data to our in-house retention time and MS/MS library created from authentic reference standards (Mass Spectrometry Metabolite Library supplied by IROA Technologies, Millipore Sigma, St. Louis, MO, USA) and online MS/MS libraries (Human Metabolome Database (HMDB, https://hmdb.ca), Mass Bank of North America (MoNA, https://mona.fiehnlab.ucdavis.edu/), and mzCloud (https://mzcloud.org). Lipid iterative MS/MS data were annotated with the Agilent Lipid Annotator software. All data files were then analyzed in Skyline (Version 20.1.0.155) to obtain peak areas. m/z values of the metabolite and lipid target lists obtained from the metabolite identification workflow, which had at least an MS/MS match to an online library, were extracted under consideration of retention times
Ion Mode:NEGATIVE
  
MS ID:MS002784
Analysis ID:AN002995
Instrument Name:Agilent 6545 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:Lipids were detected in positive and negative ion mode with the following source parameters: gas temperature 250°C, drying gas flow 11 L/min, nebulizer pressure 35 psi, sheath gas temperature 300°C, sheath gas flow 12 L/min, VCap 3000 V, nozzle voltage 500 V, Fragmentor 160 V, Skimmer 65 V, Oct 1 RF Vpp 750 V, and m/z range 50-1700. Data were acquired under continuous reference mass correction at m/z 121.0509 and 922.0890 in positive ion mode and m/z 119.0363 and 966.0007 in negative ion mode. Polar metabolite identifications were supported by matching the retention time, accurate mass, and MS/MS fragmentation data to our in-house retention time and MS/MS library created from authentic reference standards (Mass Spectrometry Metabolite Library supplied by IROA Technologies, Millipore Sigma, St. Louis, MO, USA) and online MS/MS libraries (Human Metabolome Database (HMDB, https://hmdb.ca), Mass Bank of North America (MoNA, https://mona.fiehnlab.ucdavis.edu/), and mzCloud (https://mzcloud.org). Lipid iterative MS/MS data were annotated with the Agilent Lipid Annotator software. All data files were then analyzed in Skyline (Version 20.1.0.155) to obtain peak areas. m/z values of the metabolite and lipid target lists obtained from the metabolite identification workflow, which had at least an MS/MS match to an online library, were extracted under consideration of retention times
Ion Mode:POSITIVE
  
MS ID:MS002785
Analysis ID:AN002996
Instrument Name:Agilent 6545 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:Lipids were detected in positive and negative ion mode with the following source parameters: gas temperature 250°C, drying gas flow 11 L/min, nebulizer pressure 35 psi, sheath gas temperature 300°C, sheath gas flow 12 L/min, VCap 3000 V, nozzle voltage 500 V, Fragmentor 160 V, Skimmer 65 V, Oct 1 RF Vpp 750 V, and m/z range 50-1700. Data were acquired under continuous reference mass correction at m/z 121.0509 and 922.0890 in positive ion mode and m/z 119.0363 and 966.0007 in negative ion mode. Polar metabolite identifications were supported by matching the retention time, accurate mass, and MS/MS fragmentation data to our in-house retention time and MS/MS library created from authentic reference standards (Mass Spectrometry Metabolite Library supplied by IROA Technologies, Millipore Sigma, St. Louis, MO, USA) and online MS/MS libraries (Human Metabolome Database (HMDB, https://hmdb.ca), Mass Bank of North America (MoNA, https://mona.fiehnlab.ucdavis.edu/), and mzCloud (https://mzcloud.org). Lipid iterative MS/MS data were annotated with the Agilent Lipid Annotator software. All data files were then analyzed in Skyline (Version 20.1.0.155) to obtain peak areas. m/z values of the metabolite and lipid target lists obtained from the metabolite identification workflow, which had at least an MS/MS match to an online library, were extracted under consideration of retention times
Ion Mode:NEGATIVE
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