{ "METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002829","ANALYSIS_ID":"AN004620","VERSION":"1","CREATED_ON":"August 25, 2023, 8:53 am"}, "PROJECT":{"PROJECT_TITLE":"Nucleotide, phospholipid, and kynurenine metabolites are robustly associated with COVID-19 severity and time of plasma sample collection in a prospective cohort study","PROJECT_SUMMARY":"Introduction: 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","DEPARTMENT":"Division of Preclinical Innovation - National Center for Advancing Translational Sciences","LABORATORY":"Informatics Core","LAST_NAME":"Chatelaine","FIRST_NAME":"Haley","ADDRESS":"9800 Medical Center Drive","EMAIL":"haley.chatelaine@nih.gov","PHONE":"952-738-2061"}, "STUDY":{"STUDY_TITLE":"Nucleotide, phospholipid, and kynurenine metabolites are robustly associated with COVID-19 severity and time of plasma sample collection in a prospective cohort study","STUDY_SUMMARY":"Introduction: 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","DEPARTMENT":"Division of Preclinical Innovation - National Center for Advancing Translational Sciences","LABORATORY":"Informatics Core - Division of Preclinical Innovation","LAST_NAME":"Chatelaine","FIRST_NAME":"Haley","ADDRESS":"9800 Medical Center Drive","EMAIL":"haley.chatelaine@nih.gov","PHONE":"952-738-2061","NUM_GROUPS":"4","TOTAL_SUBJECTS":"609","NUM_MALES":"232","NUM_FEMALES":"377"}, "SUBJECT":{"SUBJECT_TYPE":"Human","SUBJECT_SPECIES":"Homo sapiens","TAXONOMY_ID":"9606","AGE_OR_AGE_RANGE":"35 - 69","GENDER":"Male and female","HUMAN_RACE":"Black, White, Other","HUMAN_ETHNICITY":"Hispanic, Non-Hispanic","HUMAN_SMOKING_STATUS":"Yes or No","HUMAN_INCLUSION_CRITERIA":"positive COVID-19 diagnosis and plasma sample available"}, "SUBJECT_SAMPLE_FACTORS":[ { "Subject ID":"-", "Sample ID":"NATS-00260", "Factors":{"Sex":"Female","Severity_Scale":"3","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"52","BMIBeforeCOVID-19MedianValue":"46.59","collection_date":"10/18/10","COVID-19_confirm_date":"4/6/20","days_btwn_diagnosis":"-3458"} }, { "Subject ID":"-", "Sample ID":"NATS-00261", "Factors":{"Sex":"Male","Severity_Scale":"0","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"53","BMIBeforeCOVID-19MedianValue":"35.96","collection_date":"1/7/11","COVID-19_confirm_date":"5/11/20","days_btwn_diagnosis":"-3412"} }, { "Subject ID":"-", "Sample ID":"NATS-00262", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"62","BMIBeforeCOVID-19MedianValue":"41.9","collection_date":"1/11/11","COVID-19_confirm_date":"3/28/20","days_btwn_diagnosis":"-3364"} }, { "Subject ID":"-", "Sample ID":"NATS-00263", "Factors":{"Sex":"Female","Severity_Scale":"1","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"63","BMIBeforeCOVID-19MedianValue":"38.58","collection_date":"3/11/11","COVID-19_confirm_date":"4/3/20","days_btwn_diagnosis":"-3311"} }, { "Subject ID":"-", "Sample ID":"NATS-00264", "Factors":{"Sex":"Female","Severity_Scale":"1","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"68","BMIBeforeCOVID-19MedianValue":"25.87","collection_date":"3/11/11","COVID-19_confirm_date":"9/24/20","days_btwn_diagnosis":"-3485"} }, { "Subject ID":"-", "Sample ID":"NATS-00265", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"58","BMIBeforeCOVID-19MedianValue":"37.94","collection_date":"11/16/12","COVID-19_confirm_date":"4/15/20","days_btwn_diagnosis":"-2707"} }, { "Subject ID":"-", "Sample ID":"NATS-00266", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"58","BMIBeforeCOVID-19MedianValue":"28.04","collection_date":"9/12/12","COVID-19_confirm_date":"4/16/20","days_btwn_diagnosis":"-2773"} }, { "Subject ID":"-", "Sample ID":"NATS-00267", "Factors":{"Sex":"Female","Severity_Scale":"1","Race":"Other","Ethnicity":"Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"39","BMIBeforeCOVID-19MedianValue":"31.53","collection_date":"12/17/12","COVID-19_confirm_date":"9/3/20","days_btwn_diagnosis":"-2817"} }, { "Subject ID":"-", "Sample ID":"NATS-00268", "Factors":{"Sex":"Male","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"49","BMIBeforeCOVID-19MedianValue":"35.58","collection_date":"8/29/12","COVID-19_confirm_date":"3/30/20","days_btwn_diagnosis":"-2770"} }, { "Subject ID":"-", "Sample ID":"NATS-00269", "Factors":{"Sex":"Female","Severity_Scale":"3","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"66","BMIBeforeCOVID-19MedianValue":"41.5","collection_date":"8/29/12","COVID-19_confirm_date":"4/17/20","days_btwn_diagnosis":"-2788"} }, { "Subject ID":"-", "Sample ID":"NATS-00270", "Factors":{"Sex":"Male","Severity_Scale":"3","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"81","BMIBeforeCOVID-19MedianValue":"39.75","collection_date":"2/12/13","COVID-19_confirm_date":"4/20/20","days_btwn_diagnosis":"-2624"} }, { "Subject ID":"-", "Sample ID":"NATS-00271", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"81","BMIBeforeCOVID-19MedianValue":"28.91","collection_date":"8/10/12","COVID-19_confirm_date":"4/5/20","days_btwn_diagnosis":"-2795"} }, { "Subject ID":"-", "Sample ID":"NATS-00272", "Factors":{"Sex":"Female","Severity_Scale":"3","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"57","BMIBeforeCOVID-19MedianValue":"33.3","collection_date":"9/4/12","COVID-19_confirm_date":"4/5/20","days_btwn_diagnosis":"-2770"} }, { "Subject ID":"-", "Sample ID":"NATS-00273", "Factors":{"Sex":"Female","Severity_Scale":"2","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"70","BMIBeforeCOVID-19MedianValue":"32.19","collection_date":"7/16/12","COVID-19_confirm_date":"4/5/20","days_btwn_diagnosis":"-2820"} }, { "Subject ID":"-", "Sample ID":"NATS-00274", "Factors":{"Sex":"Male","Severity_Scale":"0","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"37","BMIBeforeCOVID-19MedianValue":"32.03","collection_date":"1/31/12","COVID-19_confirm_date":"4/25/20","days_btwn_diagnosis":"-3007"} }, { "Subject ID":"-", "Sample ID":"NATS-00275", "Factors":{"Sex":"Female","Severity_Scale":"1","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"42","BMIBeforeCOVID-19MedianValue":"22.83","collection_date":"10/11/11","COVID-19_confirm_date":"4/3/20","days_btwn_diagnosis":"-3097"} }, { "Subject ID":"-", "Sample ID":"NATS-00276", "Factors":{"Sex":"Female","Severity_Scale":"3","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"64","BMIBeforeCOVID-19MedianValue":"29.79","collection_date":"7/13/11","COVID-19_confirm_date":"7/7/20","days_btwn_diagnosis":"-3282"} }, { "Subject ID":"-", "Sample ID":"NATS-00277", "Factors":{"Sex":"Male","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"51","BMIBeforeCOVID-19MedianValue":"25.015","collection_date":"7/5/11","COVID-19_confirm_date":"7/24/20","days_btwn_diagnosis":"-3307"} }, { "Subject ID":"-", "Sample ID":"NATS-00278", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Other","Ethnicity":"Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"62","BMIBeforeCOVID-19MedianValue":"34.935","collection_date":"6/29/11","COVID-19_confirm_date":"4/30/20","days_btwn_diagnosis":"-3228"} }, { "Subject ID":"-", "Sample ID":"NATS-00279", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Other","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"43","BMIBeforeCOVID-19MedianValue":"32.785","collection_date":"8/10/11","COVID-19_confirm_date":"4/6/20","days_btwn_diagnosis":"-3162"} }, { "Subject ID":"-", "Sample ID":"NATS-00280", "Factors":{"Sex":"Female","Severity_Scale":"1","Race":"Other","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"62","BMIBeforeCOVID-19MedianValue":"38.08","collection_date":"1/19/11","COVID-19_confirm_date":"6/8/20","days_btwn_diagnosis":"-3428"} }, { "Subject ID":"-", "Sample ID":"NATS-00281", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"41","BMIBeforeCOVID-19MedianValue":"26.91","collection_date":"9/21/11","COVID-19_confirm_date":"4/10/20","days_btwn_diagnosis":"-3124"} }, { "Subject ID":"-", "Sample ID":"NATS-00282", "Factors":{"Sex":"Male","Severity_Scale":"3","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"52","BMIBeforeCOVID-19MedianValue":"34.72","collection_date":"10/5/11","COVID-19_confirm_date":"3/14/20","days_btwn_diagnosis":"-3083"} }, { "Subject ID":"-", "Sample ID":"NATS-00283", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Other","Ethnicity":"Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"50","BMIBeforeCOVID-19MedianValue":"38.98","collection_date":"10/14/11","COVID-19_confirm_date":"3/27/20","days_btwn_diagnosis":"-3087"} }, { "Subject ID":"-", "Sample ID":"NATS-00284", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Other","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"36","BMIBeforeCOVID-19MedianValue":"36.465","collection_date":"11/9/11","COVID-19_confirm_date":"9/23/20","days_btwn_diagnosis":"-3241"} }, { "Subject ID":"-", "Sample ID":"NATS-00285", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"43","BMIBeforeCOVID-19MedianValue":"50.5","collection_date":"1/25/12","COVID-19_confirm_date":"8/2/20","days_btwn_diagnosis":"-3112"} }, { "Subject ID":"-", "Sample ID":"NATS-00286", "Factors":{"Sex":"Female","Severity_Scale":"2","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"52","BMIBeforeCOVID-19MedianValue":"19.835","collection_date":"4/4/12","COVID-19_confirm_date":"4/17/20","days_btwn_diagnosis":"-2935"} }, { "Subject ID":"-", "Sample ID":"NATS-00287", "Factors":{"Sex":"Female","Severity_Scale":"3","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"71","BMIBeforeCOVID-19MedianValue":"26.85","collection_date":"5/31/11","COVID-19_confirm_date":"5/4/20","days_btwn_diagnosis":"-3261"} }, { "Subject ID":"-", "Sample ID":"NATS-00288", "Factors":{"Sex":"Male","Severity_Scale":"1","Race":"Other","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"53","BMIBeforeCOVID-19MedianValue":"39.78","collection_date":"5/9/11","COVID-19_confirm_date":"4/28/20","days_btwn_diagnosis":"-3277"} }, { "Subject ID":"-", "Sample ID":"NATS-00289", "Factors":{"Sex":"Male","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"35","BMIBeforeCOVID-19MedianValue":"33.2","collection_date":"2/14/11","COVID-19_confirm_date":"3/20/20","days_btwn_diagnosis":"-3322"} }, { "Subject ID":"-", "Sample ID":"NATS-00290", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"41","BMIBeforeCOVID-19MedianValue":"31.41","collection_date":"4/13/11","COVID-19_confirm_date":"8/22/20","days_btwn_diagnosis":"-3419"} }, { "Subject ID":"-", "Sample ID":"NATS-00291", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Other","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"46","BMIBeforeCOVID-19MedianValue":"34.1","collection_date":"1/21/11","COVID-19_confirm_date":"8/5/20","days_btwn_diagnosis":"-3484"} }, { "Subject ID":"-", "Sample ID":"NATS-00295", "Factors":{"Sex":"Male","Severity_Scale":"0","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"65","BMIBeforeCOVID-19MedianValue":"26.7","collection_date":"5/29/13","COVID-19_confirm_date":"4/9/20","days_btwn_diagnosis":"-2507"} }, { "Subject ID":"-", "Sample ID":"NATS-00296", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"30","BMIBeforeCOVID-19MedianValue":"34.83","collection_date":"6/13/13","COVID-19_confirm_date":"6/6/20","days_btwn_diagnosis":"-2550"} }, { "Subject ID":"-", "Sample ID":"NATS-00297", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"45","BMIBeforeCOVID-19MedianValue":"32.93","collection_date":"1/15/13","COVID-19_confirm_date":"4/28/20","days_btwn_diagnosis":"-2660"} }, { "Subject ID":"-", "Sample ID":"NATS-00298", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"45","BMIBeforeCOVID-19MedianValue":"36.89","collection_date":"2/15/13","COVID-19_confirm_date":"9/27/20","days_btwn_diagnosis":"-2781"} }, { "Subject ID":"-", "Sample ID":"NATS-00299", "Factors":{"Sex":"Male","Severity_Scale":"0","Race":"Other","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"64","BMIBeforeCOVID-19MedianValue":"32.97","collection_date":"9/19/13","COVID-19_confirm_date":"4/1/20","days_btwn_diagnosis":"-2386"} }, { "Subject ID":"-", "Sample ID":"NATS-00300", "Factors":{"Sex":"Male","Severity_Scale":"3","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"77","BMIBeforeCOVID-19MedianValue":"34.345","collection_date":"1/7/13","COVID-19_confirm_date":"5/2/20","days_btwn_diagnosis":"-2672"} }, { "Subject ID":"-", "Sample ID":"NATS-00301", "Factors":{"Sex":"Female","Severity_Scale":"1","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"53","BMIBeforeCOVID-19MedianValue":"27.97","collection_date":"4/12/13","COVID-19_confirm_date":"4/28/20","days_btwn_diagnosis":"-2573"} }, { "Subject ID":"-", "Sample ID":"NATS-00302", "Factors":{"Sex":"Female","Severity_Scale":"3","Race":"Other","Ethnicity":"Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"58","BMIBeforeCOVID-19MedianValue":"30.16","collection_date":"7/29/13","COVID-19_confirm_date":"3/27/20","days_btwn_diagnosis":"-2433"} }, { "Subject ID":"-", "Sample ID":"NATS-00303", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"22","BMIBeforeCOVID-19MedianValue":"24.21","collection_date":"7/22/13","COVID-19_confirm_date":"6/4/20","days_btwn_diagnosis":"-2509"} }, { "Subject ID":"-", "Sample ID":"NATS-00304", "Factors":{"Sex":"Male","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"72","BMIBeforeCOVID-19MedianValue":"35.235","collection_date":"7/22/13","COVID-19_confirm_date":"4/29/20","days_btwn_diagnosis":"-2473"} }, { "Subject ID":"-", "Sample ID":"NATS-00305", "Factors":{"Sex":"Male","Severity_Scale":"3","Race":"Other","Ethnicity":"Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"62","BMIBeforeCOVID-19MedianValue":"26.9","collection_date":"10/7/13","COVID-19_confirm_date":"5/7/20","days_btwn_diagnosis":"-2404"} }, { "Subject ID":"-", "Sample ID":"NATS-00306", "Factors":{"Sex":"Male","Severity_Scale":"1","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"41","BMIBeforeCOVID-19MedianValue":"34.18","collection_date":"8/12/13","COVID-19_confirm_date":"4/30/20","days_btwn_diagnosis":"-2453"} }, { "Subject ID":"-", "Sample ID":"NATS-00307", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"53","BMIBeforeCOVID-19MedianValue":"32.34","collection_date":"8/7/13","COVID-19_confirm_date":"4/25/20","days_btwn_diagnosis":"-2453"} }, { "Subject ID":"-", "Sample ID":"NATS-00308", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"59","BMIBeforeCOVID-19MedianValue":"29.645","collection_date":"11/28/16","COVID-19_confirm_date":"3/25/20","days_btwn_diagnosis":"-1213"} }, { "Subject ID":"-", "Sample ID":"NATS-00309", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"47","BMIBeforeCOVID-19MedianValue":"25.45","collection_date":"9/23/13","COVID-19_confirm_date":"5/2/20","days_btwn_diagnosis":"-2413"} }, { "Subject ID":"-", "Sample ID":"NATS-00310", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"57","BMIBeforeCOVID-19MedianValue":"36.28","collection_date":"7/26/13","COVID-19_confirm_date":"4/27/20","days_btwn_diagnosis":"-2467"} }, { "Subject ID":"-", "Sample ID":"NATS-00311", "Factors":{"Sex":"Male","Severity_Scale":"1","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"69","BMIBeforeCOVID-19MedianValue":"29.69","collection_date":"6/13/13","COVID-19_confirm_date":"6/19/20","days_btwn_diagnosis":"-2563"} }, { "Subject ID":"-", "Sample ID":"NATS-00313", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"pre-COVID-19"}, "Additional sample data":{"Plasma_Age":"54","BMIBeforeCOVID-19MedianValue":"35.29","collection_date":"9/26/13","COVID-19_confirm_date":"4/16/20","days_btwn_diagnosis":"-2394"} }, { "Subject ID":"-", "Sample ID":"NATS-00314", 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data":{"Plasma_Age":"42","BMIBeforeCOVID-19MedianValue":"24.21","collection_date":"6/18/20","COVID-19_confirm_date":"3/11/20","days_btwn_diagnosis":"99"} }, { "Subject ID":"-", "Sample ID":"NATS-01134", "Factors":{"Sex":"Male","Severity_Scale":"2","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"1","Time":"post-COVID-19"}, "Additional sample data":{"Plasma_Age":"62","BMIBeforeCOVID-19MedianValue":"32.08","collection_date":"7/30/20","COVID-19_confirm_date":"5/22/20","days_btwn_diagnosis":"69"} }, { "Subject ID":"-", "Sample ID":"NATS-01160", "Factors":{"Sex":"Female","Severity_Scale":"1","Race":"Black","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"post-COVID-19"}, "Additional sample data":{"Plasma_Age":"24","BMIBeforeCOVID-19MedianValue":"21.305","collection_date":"9/11/20","COVID-19_confirm_date":"5/22/20","days_btwn_diagnosis":"112"} }, { "Subject ID":"-", "Sample ID":"NATS-01161", "Factors":{"Sex":"Female","Severity_Scale":"3","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"post-COVID-19"}, "Additional sample data":{"Plasma_Age":"43","BMIBeforeCOVID-19MedianValue":"43.575","collection_date":"7/29/20","COVID-19_confirm_date":"5/15/20","days_btwn_diagnosis":"75"} }, { "Subject ID":"-", "Sample ID":"NATS-01163", "Factors":{"Sex":"Male","Severity_Scale":"2","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"post-COVID-19"}, "Additional sample data":{"Plasma_Age":"71","BMIBeforeCOVID-19MedianValue":"39.27","collection_date":"6/16/20","COVID-19_confirm_date":"5/17/20","days_btwn_diagnosis":"30"} }, { "Subject ID":"-", "Sample ID":"NATS-01171", "Factors":{"Sex":"Female","Severity_Scale":"2","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"post-COVID-19"}, "Additional sample data":{"Plasma_Age":"49","BMIBeforeCOVID-19MedianValue":"38.44","collection_date":"8/28/20","COVID-19_confirm_date":"3/31/20","days_btwn_diagnosis":"150"} }, { "Subject ID":"-", "Sample ID":"NATS-01174", "Factors":{"Sex":"Female","Severity_Scale":"0","Race":"White","Ethnicity":"Non-Hispanic","hasSmokingBeforeCOVID-19":"0","Time":"post-COVID-19"}, "Additional sample data":{"Plasma_Age":"36","BMIBeforeCOVID-19MedianValue":"35.34","collection_date":"8/24/20","COVID-19_confirm_date":"3/28/20","days_btwn_diagnosis":"149"} } ], "COLLECTION":{"COLLECTION_SUMMARY":"The Mass General Brigham (MGB) Biobank contains ~100,000 banked plasma, serum, and DNA samples from >100,000 consented patients. Electronic Medical Record (EMR) data and lifestyle, environment, and family history surveys can also be linked to the banked samples. The Longitudinal EMR and Omics COVID-19 Cohort (LEOCC) consists of a subset of individuals with prospective plasma samples from the MGB Biobank. Patients with a positive COVID-19 diagnosis (defined as a COVID-19 positive infection control flag, COVID-19 presumed infection control flag, or SARS-CoV-2 RNA positive test result) and available plasma samples prior to COVID-19 (up to October 27, 2020) were included. No additional exclusion criteria were applied. Clinical data relevant to COVID-19 infection, including clinical measures, disease diagnoses, and COVID-19 severity were also extracted from EMR data for use in statistical models. This study was approved by the Brigham and Women’s Institutional Review Board (IRB: 2014P001109). A total of 940 plasma samples from 661 individuals were collected from consented patients and were stored at –80 C. These samples are categorized by the time point of collection relative to a positive COVID-19 diagnosis, including 474 pre-COVID-19 samples (date of collection < date of diagnosis), 282 during COVID-19 samples (collected within 28 days of diagnosis), and 182 post-COVID-19 samples (collected more than 28 days after COVID-19 diagnosis). For patients with multiple during and/or post-COVID-19 samples, only the sample collected at the date closest to diagnosis was retained for during-COVID-19, and only the sample collected at the date furthest from diagnosis was retained for post-COVID-19. Patients without BMI data were also excluded from the sample sets, yielding a total of n = 441 pre-COVID-19, n = 86 during COVID-19, and n = 82 post-COVID-19 samples used for analysis.","SAMPLE_TYPE":"Blood (plasma)"}, "TREATMENT":{"TREATMENT_SUMMARY":"The COVID-19 severity level was determined according to WHO guidelines (16) as 0 = ambulatory mild disease (no hospitalization), 1 = hospitalized moderate disease (hospitalized without ventilation), 2 = hospitalized severe disease (hospitalized with ventilation), or 3 = death. Further demographic, risk factor, and comorbidity covariables were defined before COVID-19 diagnosis for all patients as follows: age is the numerical patient age; race is categorical (black, other, white); ethnicity (Hispanic/non-Hispanic), sex (female/male), and smoking (yes/no) are binary; BMI is the numerical median body mass index (BMI) for each patient; and comorbidity level is a binary “mild” or “severe” factor based on a Charlson index < 5 or ≥ 5, respectively."}, "SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Plasma samples were sent to Metabolon for comprehensive metabolomic profiling of polar and nonpolar metabolite classes in plasma extracts. Samples were extracted and prepared according to methods published previously (19)."}, "CHROMATOGRAPHY":{"CHROMATOGRAPHY_SUMMARY":"Low pH Lipophilic (LC/MS Pos late)","CHROMATOGRAPHY_TYPE":"Reversed phase","INSTRUMENT_NAME":"Waters Acquity","COLUMN_NAME":"Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)","SOLVENT_A":"-","SOLVENT_B":"-","FLOW_GRADIENT":"-","FLOW_RATE":"-","COLUMN_TEMPERATURE":"-"}, "ANALYSIS":{"ANALYSIS_TYPE":"MS","ANALYSIS_PROTOCOL_FILE":"Metabolon_Data_Filtering_and_Normalization_LEOCC.pdf"}, "MS":{"INSTRUMENT_NAME":"Thermo Q Exactive Orbitrap","INSTRUMENT_TYPE":"Orbitrap","MS_TYPE":"Other","ION_MODE":"POSITIVE","MS_COMMENTS":"Metabolon (LC/MS Pos late)"}, "MS_METABOLITE_DATA":{ "Units":"log transformed data", 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