ABSTRACT
Background: The mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why unvaccinated individuals remain uninfected despite high-risk exposures. Objective: to understand lipid and metabolite profiles related with COVID-19 susceptibility and disease progression. Methods: we collected samples from an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 but not infected (‘non-susceptible’) and subjects who became infected during the follow-up (‘susceptible’), including non-hospitalized and hospitalized patients with different disease severity providing samples at early disease stages. Then, we analyzed their plasma metabolomic profiles using mass spectrometry coupled with liquid and gas chromatography. Results:we show specific lipids profiles and metabolites that could explain SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, non-susceptible individuals show a unique lipidomic pattern characterized by the upregulation of most lipids, especially ceramides and sphingomyelin, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. Conclusion: this study strengthens the findings of other researchers about the importance of studying lipid profiles as relevant markers of SARS-CoV-2 pathogenesis.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Despite of 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 early after symptom onset who were prospectively followed and 29 healthcare workers heavily exposed to SARS-CoV-2 but with low susceptibility to infection ( nonsusceptible). We found that the metabolite profile was predictive of the study group. We identified a total of 55 metabolites as biomarkers 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, citrate, and BAIBA), energy production and amino acid catabolism (L-glycine, L-alanine, L-serine, L-proline, L-aspartic acid and L-histidine), endothelial dysfunction and thrombosis (citrulline, L-ADMA, 2-AB, and Neu5Ac), and we found interconnections between these pathways. In summary, in this first report of the metabolomic profile of individuals with severe COVID-19 and SARS-CoV-2 susceptibility by CE-MS, we define several metabolic pathways implicated in SARS-CoV-2 susceptibility and COVID-19 clinical progression that could be developed as biomarkers of COVID-19.