Summary of Study ST002829

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 PR001771. The data can be accessed directly via it's Project DOI: 10.21228/M8SM6H 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 IDST002829
Study TitleNucleotide, phospholipid, and kynurenine metabolites are robustly associated with COVID-19 severity and time of plasma sample collection in a prospective cohort study
Study SummaryIntroduction: A deep understanding of the molecular underpinnings of disease severity and progression in large human studies is necessary to develop metabolism-related preventive strategies of severe disease outcomes, particularly in viral pandemics like that of COVID-19. The use of samples collected before disease diagnosis, however, is limited and thus metabolites and metabolic pathways that predispose to severe disease are not well understood. Further, current studies are limited in sample size, number of metabolites evaluated, and/or do not adjust for comorbidities. Methods: We generated comprehensive plasma metabolomic profiles in more than 600 patients from the Longitudinal EMR and Omics COVID-19 Cohort (LEOCC). Samples were collected before (n = 441), during (n = 86), and after (n = 82) COVID-19 diagnosis. Regression models were used to determine (1) metabolites associated with predisposition to and/or persistent effects of COVID-19 severity within each time of sample collection, using logistic regression and (2) metabolites associated with time of sample collection, using linear regression, to better understand transient or lingering metabolic alterations over the disease course. All models were controlled for demographic (age, sex, race, ethnicity), risk (smoking status, BMI), and comorbidities (Charlson Index). Metabolites with an FDR-adjusted p-value < 0.05 were considered significant. Results: Of the 1,546 metabolites measured, 506 were associated with disease severity or time of sample collection. Among these, sphingolipids and phospholipids were negatively associated with severity and exhibited lingering elevations after disease, while modified nucleotides were positively associated with severity and had lingering decreases after disease. Cytidine and uridine metabolites, which were positively and negatively associated with COVID-19 severity, respectively, were transiently elevated in active disease, reflecting particular importance of pyrimidine metabolism in active COVID-19. Conclusions: We identified novel metabolites reflecting predisposition to severe disease and changes to global metabolism from before to during and after COVID-19 diagnosis. This is the first large metabolomics study using COVID-19 plasma samples before, during, and/or after disease. This study lays the groundwork for identifying putative clinical biomarkers and identifying preventative strategies for severe disease outcomes.
Institute
National Institutes of Health
DepartmentDivision of Preclinical Innovation - National Center for Advancing Translational Sciences
LaboratoryInformatics Core - Division of Preclinical Innovation
Last NameChatelaine
First NameHaley
Address9800 Medical Center Drive
Emailhaley.chatelaine@nih.gov
Phone952-738-2061
Submit Date2023-08-24
Num Groups4
Total Subjects609
Num Males232
Num Females377
Analysis Type DetailOther
Release Date2023-09-19
Release Version1
Haley Chatelaine Haley Chatelaine
https://dx.doi.org/10.21228/M8SM6H
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN004619 AN004620 AN004621 AN004622
Analysis type MS MS MS MS
Chromatography type Reversed phase Reversed phase Reversed phase HILIC
Chromatography system Waters Acquity Waters Acquity Waters Acquity Waters Acquity
Column Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) Waters Acquity BEH Amide (150 x 2.1mm, 1.7um)
MS Type ESI ESI ESI ESI
MS instrument type Orbitrap Orbitrap Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE POSITIVE NEGATIVE NEGATIVE
Units log transformed data log transformed data log transformed data log transformed data

Chromatography:

Chromatography ID:CH003475
Chromatography Summary:Low pH polar (LC/MS Pos early)
Instrument Name:Waters Acquity
Column Name:Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
Column Temperature:-
Flow Gradient:-
Flow Rate:-
Solvent A:-
Solvent B:-
Chromatography Type:Reversed phase
  
Chromatography ID:CH003476
Chromatography Summary:Low pH Lipophilic (LC/MS Pos late)
Instrument Name:Waters Acquity
Column Name:Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
Column Temperature:-
Flow Gradient:-
Flow Rate:-
Solvent A:-
Solvent B:-
Chromatography Type:Reversed phase
  
Chromatography ID:CH003477
Chromatography Summary:High pH (LC/MS Neg)
Instrument Name:Waters Acquity
Column Name:Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
Column Temperature:-
Flow Gradient:-
Flow Rate:-
Solvent A:-
Solvent B:-
Chromatography Type:Reversed phase
  
Chromatography ID:CH003478
Chromatography Summary:HILIC (LC/MS Polar Neg)
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH Amide (150 x 2.1mm, 1.7um)
Column Temperature:-
Flow Gradient:-
Flow Rate:-
Solvent A:-
Solvent B:-
Chromatography Type:HILIC
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