2aec0a15a1b062cf51bda77df1e74165 pmc_33946479.pdf 062f3e20e41b1516b4aab4b2c647d98e068aea8f pmc_33946479.pdf 99a5b581df8b751df917ce684521892f044ca10f7666f90431bf9f036a6c58be pmc_33946479.pdf Title: Metabolic Signatures Associated with Severity in Hospitalized COVID-19 Patients Subject: The clinical evolution of COVID-19 pneumonia is poorly understood. Identifying the metabolic pathways that are altered early with viral infection and their association with disease severity is crucial to understand COVID-19 pathophysiology, and guide clinical decisions. This study aimed at assessing the critical metabolic pathways altered with disease severity in hospitalized COVID-19 patients. Forty-nine hospitalized patients with COVID-19 pneumonia were enrolled in a prospective, observational, single-center study in Barcelona, Spain. Demographic, clinical, and analytical data at admission were registered. Plasma samples were collected within the first 48 h following hospitalization. Patients were stratified based on the severity of their evolution as moderate (N = 13), severe (N = 10), or critical (N = 26). A panel of 221 biomarkers was measured by targeted metabolomics in order to evaluate metabolic changes associated with subsequent disease severity. Our results show that obesity, respiratory rate, blood pressure, and oxygen saturation, as well as some analytical parameters and radiological findings, were all associated with disease severity. Additionally, ceramide metabolism, tryptophan degradation, and reductions in several metabolic reactions involving nicotinamide adenine nucleotide (NAD) at inclusion were significantly associated with respiratory severity and correlated with inflammation. In summary, assessment of the metabolomic profile of COVID-19 patients could assist in disease severity stratification and even in guiding clinical decisions. Keywords: COVID-19; metabolomics; severity; kynurenine; ceramides Author: Judith Marín-Corral, Jose Rodríguez-Morató, Alex Gomez-Gomez, Sergi Pascual-Guardia, Rosana Muñoz-Bermúdez, Anna Salazar-Degracia, Purificación Pérez-Terán, Marcos I. Restrepo, Olha Khymenets, Noemí Haro, Joan Ramon Masclans and Oscar J. Pozo Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sun May 2 03:55:57 2021 CEST ModDate: Sat May 8 13:14:53 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2529938 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MZCZTZ+VnURWPalladioL Type 1 Custom yes yes no 10 0 MFXOJV+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 RJBSQB+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 UAFCPO+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 DGBDNV+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 36 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 61 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 65 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 69 0 IBIKHZ+CMSY10 Type 1 Builtin yes yes no 85 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 92 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 96 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 100 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 104 0 VVSYYB+EURM10 Type 1 Builtin yes yes no 120 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 131 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 135 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 139 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 143 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 158 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 162 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 166 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 170 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 187 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 191 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 195 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 199 0 ABCDEE+Palatino Linotype,Bold TrueType WinAnsi yes yes no 216 0 ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 220 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 224 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 228 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-10-21 02:38:18 CEST RepresentationInformation: pmc_33946479.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:09:54 CEST Size: 2529938 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 372 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Characteristics of Patients Based on Severity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Metabolomics Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Children: Item: Title: Study Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Patients and Selection Criteria Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Variables Analyzed Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Study Groups Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Sample Collection and Metabolomics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Info: Title: Metabolic Signatures Associated with Severity in Hospitalized COVID-19 Patients Author: Judith Marín-Corral, Jose Rodríguez-Morató, Alex Gomez-Gomez, Sergi Pascual-Guardia, Rosana Muñoz-Bermúdez, Anna Salazar-Degracia, Purificación Pérez-Terán, Marcos I. Restrepo, Olha Khymenets, Noemí Haro, Joan Ramon Masclans and Oscar J. Pozo Subject: The clinical evolution of COVID-19 pneumonia is poorly understood. Identifying the metabolic pathways that are altered early with viral infection and their association with disease severity is crucial to understand COVID-19 pathophysiology, and guide clinical decisions. This study aimed at assessing the critical metabolic pathways altered with disease severity in hospitalized COVID-19 patients. Forty-nine hospitalized patients with COVID-19 pneumonia were enrolled in a prospective, observational, single-center study in Barcelona, Spain. Demographic, clinical, and analytical data at admission were registered. Plasma samples were collected within the first 48 h following hospitalization. Patients were stratified based on the severity of their evolution as moderate (N = 13), severe (N = 10), or critical (N = 26). A panel of 221 biomarkers was measured by targeted metabolomics in order to evaluate metabolic changes associated with subsequent disease severity. Our results show that obesity, respiratory rate, blood pressure, and oxygen saturation, as well as some analytical parameters and radiological findings, were all associated with disease severity. Additionally, ceramide metabolism, tryptophan degradation, and reductions in several metabolic reactions involving nicotinamide adenine nucleotide (NAD) at inclusion were significantly associated with respiratory severity and correlated with inflammation. In summary, assessment of the metabolomic profile of COVID-19 patients could assist in disease severity stratification and even in guiding clinical decisions. 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