Metabolic Snapshot of Plasma Samples Reveals New Pathways Implicated in SARS-CoV-2 Pathogenesis

Oihane E. Albóniga, Daniel Jiménez, Matilde Sánchez-Conde, Pilar Vizcarra, Raquel Ron, Sabina Herrera, Javier Martínez-Sanz, Elena Moreno, Santiago Moreno, Coral Barbas, Sergio Serrano-Villar

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Despite the scientific and human efforts to understand COVID-19, there are questions still unanswered. Variations in the metabolic reaction to SARS-CoV-2 infection could explain the striking differences in the susceptibility to infection and the risk of severe disease. Here, we used untargeted metabolomics to examine novel metabolic pathways related to SARS-CoV-2 susceptibility and COVID-19 clinical severity using capillary electrophoresis coupled to a time-of-flight mass spectrometer (CE-TOF-MS) in plasma samples. We included 27 patients with confirmed COVID-19 and 29 healthcare workers heavily exposed to SARS-CoV-2 but with low susceptibility to infection (“nonsusceptible”). We found a total of 42 metabolites of SARS-CoV-2 susceptibility or COVID-19 clinical severity. We report the discovery of new plasma biomarkers for COVID-19 that provide mechanistic explanations for the clinical consequences of SARS-CoV-2, including mitochondrial and liver dysfunction as a consequence of hypoxemia (citrulline, citric acid, and 3-aminoisobutyric acid (BAIBA)), energy production and amino acid catabolism (phenylalanine and histidine), and endothelial dysfunction and thrombosis (citrulline, asymmetric dimethylarginine (ADMA), and 2-aminobutyric acid (2-AB)), and we found interconnections between these pathways. In summary, in this first report several metabolic pathways implicated in SARS-CoV-2 susceptibility and COVID-19 clinical progression were found by CE-MS based metabolomics that could be developed as biomarkers of COVID-19.

Original languageEnglish
Pages (from-to)623-634
Number of pages12
JournalJournal of Proteome Research
Volume21
Issue number3
DOIs
StatePublished - 4 Mar 2022
Externally publishedYes

Keywords

  • COVID-19
  • SARS-CoV-2
  • biomarkers
  • clinical progression
  • disease susceptibility
  • metabolites
  • metabolomics
  • oxidative stress response

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