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  2. Integrated NMR and MS Analysis of the Plasma Metabolome Reveals Major Changes in One-Carbon, Lipid, and Amino Acid Metabolism in Severe and Fatal Cases of COVID-19

Integrated NMR and MS Analysis of the Plasma Metabolome Reveals Major Changes in One-Carbon, Lipid, and Amino Acid Metabolism in Severe and Fatal Cases of COVID-19

  • Metabolites. 2023 Jul 24;13(7):879. doi: 10.3390/metabo13070879.
Marcos C Gama-Almeida 1 Gabriela D A Pinto 1 Lívia Teixeira 2 Eugenio D Hottz 3 Paula Ivens 4 Hygor Ribeiro 4 5 Rafael Garrett 4 Alexandre G Torres 1 5 Talita I A Carneiro 1 Bianca de O Barbalho 1 Christian Ludwig 6 Claudio J Struchiner 7 8 Iranaia Assunção-Miranda 9 Ana Paula C Valente 10 Fernando A Bozza 11 12 Patrícia T Bozza 2 Gilson C Dos Santos Jr 13 Tatiana El-Bacha 1 5
Affiliations

Affiliations

  • 1 LeBioME-Bioactives, Mitochondrial and Placental Metabolism Core, Institute of Nutrition Josué de Castro, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
  • 2 Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21041-361, Brazil.
  • 3 Laboratory of Immunothrombosis, Department of Biochemistry, Federal University of Juiz de Fora, Juiz de Fora 36936-900, Brazil.
  • 4 LabMeta, Metabolomics Laboratory, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-598, Brazil.
  • 5 Lipid Biochemistry and Lipidomics Laboratory, Department of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-598, Brazil.
  • 6 Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2SQ, UK.
  • 7 School of Applied Mathematics, Fundação Getúlio Vargas, Rio de Janeiro 22231-080, Brazil.
  • 8 Institute of Social Medicine, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-013, Brazil.
  • 9 LaRIV, Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
  • 10 National Center for Nuclear Magnetic Resonance-Jiri Jonas, Institute of Medical Biochemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
  • 11 National Institute of Infectious Disease Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro 21040-360, Brazil.
  • 12 D'Or Institute for Research and Education, Rio de Janeiro 22281-100, Brazil.
  • 13 LabMet-Laboratory of Metabolomics, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Department of Genetics, State University of Rio de Janeiro, Rio de Janeiro 20551-030, Brazil.
Abstract

Brazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients' sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.

Keywords

1H-NMR; SARS-CoV-2; fatal COVID-19; high-resolution mass spectrometry; metabolic alterations; metabolomics; sex differences; virus-host interactions.

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