Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation

Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytok...

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Detalhes bibliográficos
Autores: Ceballos, Francisco C, Virseda-Berdices, Ana, Resino, Salvador, Ryan, Pablo, Martínez-González, Oscar, Perez-Garcia, Felipe, Martin-Vicente, Maria, Brochado-Kith, Oscar, Blancas, Rafael, Bartolomé-Sánchez, Sofía, Vidal-Alcántara, Erick Joan, Albóniga-Díez, Oihane Elena, Cuadros-González, Juan, Blanca-López, Natalia, Martinez, Isidoro, Ramirez Martinez-Acitores, Ignacio, Barbas, Coral, Fernandez-Rodriguez, Amanda, Jimenez-Sousa, Maria Angeles
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/15186
Acesso em linha:http://hdl.handle.net/20.500.12105/15186
Access Level:acceso abierto
Palavra-chave:COVID-19
Cross-Sectional Studies
Cytokines
Disease Progression
Female
Humans
Kynurenine
Male
Retrospective Studies
SARS-CoV-2
Severity of Illness Index
Tryptophan
Descrição
Resumo:Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.