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

Federal University of Rio de Janeiro. Institute of Nutrition Josué de Castro. LeBioME-Bioactives. Mitochondrial and Placental Metabolism Core. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Nutrition Josué de Castro. LeBioME-Bioactives. Mitochondrial and Placental Metabolism Core. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Immunopharmacology. Rio de Janeiro, RJ, Brazil.
Federal University of Juiz de Fora. Department of Biochemistry. Laboratory of Immunothrombosis. Juiz de Fora, Brazil.
Federal University of Rio de Janeiro. Institute of Chemistry. Metabolomics Laboratory. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Chemistry. Metabolomics Laboratory. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Department of Chemistry. Lipid Biochemistry and Lipidomics Laboratory. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Chemistry. Metabolomics Laboratory. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Nutrition Josué de Castro. LeBioME-Bioactives. Mitochondrial and Placental Metabolism Core. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Department of Chemistry. Lipid Biochemistry and Lipidomics Laboratory. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Nutrition Josué de Castro. LeBioME-Bioactives. Mitochondrial and Placental Metabolism Core. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Nutrition Josué de Castro. LeBioME-Bioactives. Mitochondrial and Placental Metabolism Core. Rio de Janeiro, RJ, Brazil.
University of Birmingham. Institute of Metabolism and Systems Research. Birmingham, UK.
Getúlio Vargas Foundation. School of Applied Mathematics. Rio de Janeiro, RJ, Brazil / State University of Rio de Janeiro. Institute of Social Medicine. Rio de Janeiro, RJ, Brazil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Goes. Rio de Janeiro, RJ, Brasil.
Federal University of Rio de Janeiro. Institute of Medical Biochemistry. National Center for Nuclear Magnetic Resonance—Jiri Jonas. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. National Institute of Infectious Disease Evandro Chagas. Rio de Janeiro, RJ, Brazil / D’Or Institute for Research and Education. Rio de Janeiro, RJ, Brazil.
Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Immunopharmacology. Rio de Janeiro, RJ, Brazil.
State University of Rio de Janeiro. Roberto Alcantara Gomes Biology Institute. Department of Genetics. Laboratory of Metabolomics. Rio de Janeiro, RJ, Brazil.
Federal University of Rio de Janeiro. Institute of Nutrition Josué de Castro. LeBioME-Bioactives. Mitochondrial and Placental Metabolism Core. Rio de Janeiro, RJ, Brazil / Federal University of Rio de Janeiro. Department of Chemistry. Lipid Biochemistry and Lipidomics Laboratory. Rio de Janeiro, RJ, 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

SARS-CoV-2
Metabolomics
High-resolution mass spectrometry
Fatal COVID-19
Virus-host interactions
Metabolic alterations
Sex differences

Publisher

MDPI

Citation

GAMA-ALMEIDA, Marcos C. et al. 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, v. 13, n. 7, p. 1-23, Jul. 2023.

DOI

10.3390/metabo13070879

ISSN

2218-1989

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/61575

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Copyright

Open access

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