Summary of Study ST002291

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 PR001469. The data can be accessed directly via it's Project DOI: 10.21228/M8V134 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 IDST002291
Study TitleIntegrated metabolic and inflammatory signatures associated with severity, fatality, and recovery of COVID-19
Study TypeResearch
Study SummarySevere manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed-up after hospital discharge and recovery of acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, tryptophan and oxoproline; and lipids, including progesterone, phosphocholine and lysophosphatidylcholines (lysoPCs). Individuals that recovered from severe disease displayed persistent alterations enriched for metabolism of purines, phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19.
Institute
Federal University of Goiás
DepartmentInstitute of Tropical Pathology and Public Health
Last NameGardinassi
First NameLuiz Gustavo
AddressR. 235 s/n - Institute of Tropical Pathology and Public Health - Federal University of Goiás
Emailluizgardinassi@ufg.br
Phone+55 62 3209-6530
Submit Date2022-09-08
Raw Data AvailableYes
Raw Data File Type(s)mzXML, raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-10-19
Release Version1
Luiz Gustavo Gardinassi Luiz Gustavo Gardinassi
https://dx.doi.org/10.21228/M8V134
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001469
Project DOI:doi: 10.21228/M8V134
Project Title:Integrated metabolic and inflammatory signatures associated with severity, fatality, and recovery of COVID-19
Project Type:Research
Project Summary:Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed-up after hospital discharge and recovery of acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, tryptophan and oxoproline; and lipids, including progesterone, phosphocholine and lysophosphatidylcholines (lysoPCs). Individuals that recovered from severe disease displayed persistent alterations enriched for metabolism of purines, phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19.
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
Email:luizgardinassi@ufg.br
Phone:+55 62 3209-6530

Subject:

Subject ID:SU002377
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 Group
SA220034ID_196Control donor
SA220035ID_195Control donor
SA220036ID_194Control donor
SA220037ID_197Control donor
SA220038ID_198Control donor
SA220039ID_200Control donor
SA220040ID_199Control donor
SA220041ID_193Control donor
SA220042ID_192Control donor
SA220043ID_186Control donor
SA220044ID_182Control donor
SA220045ID_188Control donor
SA220046ID_189Control donor
SA220047ID_191Control donor
SA220048ID_190Control donor
SA220049ID_201Control donor
SA220050ID_187Control donor
SA220051ID_212Control donor
SA220052ID_211Control donor
SA220053ID_213Control donor
SA220054ID_214Control donor
SA220055ID_202Control donor
SA220056ID_240Control donor
SA220057ID_210Control donor
SA220058ID_215Control donor
SA220059ID_203Control donor
SA220060ID_204Control donor
SA220061ID_209Control donor
SA220062ID_205Control donor
SA220063ID_208Control donor
SA220064ID_206Control donor
SA220065ID_207Control donor
SA220066ID_110Fatal
SA220067ID_109Fatal
SA220068ID_108Fatal
SA220069ID_114Fatal
SA220070ID_115Fatal
SA220071ID_113Fatal
SA220072ID_112Fatal
SA220073ID_103Fatal
SA220074ID_116Fatal
SA220075ID_100Fatal
SA220076ID_101Fatal
SA220077ID_102Fatal
SA220078ID_106Fatal
SA220079ID_105Fatal
SA220080ID_107Fatal
SA220081ID_128Fatal
SA220082ID_131Fatal
SA220083ID_130Fatal
SA220084ID_132Fatal
SA220085ID_133Fatal
SA220086ID_99Fatal
SA220087ID_134Fatal
SA220088ID_129Fatal
SA220089ID_127Fatal
SA220090ID_119Fatal
SA220091ID_118Fatal
SA220092ID_120Fatal
SA220093ID_124Fatal
SA220094ID_126Fatal
SA220095ID_125Fatal
SA220096ID_117Fatal
SA220097ID_111Fatal
SA220098ID_21Fatal
SA220099ID_25Fatal
SA220100ID_7Fatal
SA220101ID_145Mild
SA220102ID_146Mild
SA220103ID_148Mild
SA220104ID_144Mild
SA220105ID_147Mild
SA220106ID_142Mild
SA220107ID_139Mild
SA220108ID_138Mild
SA220109ID_140Mild
SA220110ID_141Mild
SA220111ID_150Mild
SA220112ID_143Mild
SA220113ID_152Mild
SA220114ID_172Mild
SA220115ID_171Mild
SA220116ID_176Mild
SA220117ID_179Mild
SA220118ID_181Mild
SA220119ID_168Mild
SA220120ID_167Mild
SA220121ID_154Mild
SA220122ID_153Mild
SA220123ID_155Mild
SA220124ID_156Mild
SA220125ID_166Mild
SA220126ID_151Mild
SA220127ID_149Mild
SA220128ID_81Mild
SA220129ID_82Mild
SA220130ID_83Mild
SA220131ID_75Moderated
SA220132ID_76Moderated
SA220133ID_72Moderated
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Collection:

Collection ID:CO002370
Collection Summary:Individuals with COVID-19 were admitted to the Hospital das Clínicas and Hospital das Clínicas de Campanha or recruited at the Laboratório Profª Margarida Dobler Komma at the Federal University of Goiás, Goiânia, Brazil between June 2020 to February 2021, before vaccination rollout. Blood samples were collected in EDTA tubes from 150 individuals who had confirmed SARS-CoV-2 infection by RT-qPCR test from nasopharyngeal swabs or by serological assays to detect specific IgM/IgG antibodies (Eco diagnostics); and control donors (n=27), who were negative for SARS-CoV-2 infection confirmed by RT-qPCR from nasopharyngeal swabs and serological IgM/IgG tests.
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR002389
Treatment Summary:The criteria defined on COVID-19 Treatment Guidelines (National Institute of Health, USA) and World Health Organization [21,22] were used to stratify individuals with COVID-19 into mild disease (individuals presenting various signs and symptoms without shortness of breath, dyspnea, or abnormal chest imaging), moderate disease (individuals presenting radiologically confirmed pneumonitis, hospitalization and oxygen therapy), severe disease (dyspnea, respiratory frequency ≥30 breaths/min, saturation of oxygen [SpO2] ≤ 93%, and/or lung infiltrates >50% within 24 to 48 hours, including individuals that required monitoring and treatment in Intensive Care Unit and mechanical ventilation), or fatal COVID-19.

Sample Preparation:

Sampleprep ID:SP002383
Sampleprep Summary:For metabolomics analyses, cold acetonitrile was added to plasma samples (2:1, v/v) vortexed and centrifuged (10 min, 10000 rpm at 4 °C) for protein precipitation. Stable isotopes caffeine-¹³C3, tyrosine-15N and progesterone-d9 were used as internal standards.

Combined analysis:

Analysis ID AN003743
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1220 Infinity
Column Agilent Zorbax Eclipse Plus C18 (150 x 4.6mm,3.5um)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode POSITIVE
Units peak area

Chromatography:

Chromatography ID:CH002773
Chromatography Summary:The binary mobile phases were water 0.5% formic acid with 5 mM of ammonium formate (A), and acetonitrile (B). Their gradient elution started with 20% (B) for 5 min, then linearly increased to 100% (B) in 30 min and kept constant for 8 min in 100% (B). The eluent was restored to the initial conditions in 4 minutes to re-equilibrate the column and held for the remaining 8 minutes. The flow rate was kept at 0.5 mL min-1. The injection volume for analysis was 3 μL, and the column temperature was set at 35 °C.
Instrument Name:Agilent 1220 Infinity
Column Name:Agilent Zorbax Eclipse Plus C18 (150 x 4.6mm,3.5um)
Column Temperature:35
Flow Gradient:gradient elution started with 20% (B) for 5 min, then linearly increased to 100% (B) in 30 min and kept constant for 8 min in 100% (B). The eluent was restored to the initial conditions in 4 minutes to re-equilibrate the column and held for the remaining 8 minutes.
Flow Rate:0.5 mL/min
Solvent A:100% water; 0.5% formic acid; 5 mM of ammonium formate
Solvent B:100% acetonitrile
Chromatography Type:Reversed phase

MS:

MS ID:MS003490
Analysis ID:AN003743
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:The electrospray ionization was operating with the following settings: spray voltage 3.5 kV; capillary temperature: 269 °C; S-lens RF level 50 V; sheath gas flow rate at 53 L min-1; aux gas flow rate at 14 L min-1; sweep gas flow rate 3 L min-1. The high-resolution mass-spectrometry was obtained under full MS/dd-MS2 mode. The mass range in the full MS scanning experiments was m/z 80-1200. The max IT was set at 200 ms, and AGC target was set at 1 x 106. For fragmentation acquisition, the top 5 (TopN, 5, loop count 5) most abundant precursors were sequentially transferred into the C-Trap (AGC target 1 x 105; max IT 50 ms) for collision. The collision energy for target analytes was 20, 30 and 35 eV. Resolving power was set at 140,000 and 70,000 for full MS and dd-MS2 acquisitions, respectively. Proteowizard software was used to convert .raw files into mzXML format and apLCMS software was used to perform peak deconvolution and detection, to filter noise, to align mass-to-charge ratio (m/z) and retention time and to quantify metabolite features, which are defined by a specific m/z, retention time and intensity values for each sample.
Ion Mode:POSITIVE
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