A longitudinal comparative analysis of serum metabolomic signatures in children with SARS-CoV-2 infection and MIS-C

SARS-CoV-2 infection usually has a mild course in childhood, yet few children develop a Multisystem Inflammatory Syndrome (MIS-C). Several metabolic pathways have been found to be dysregulated in adults with COVID-19, yet data are lacking in children. Here we investigate serum metabolomic features of children with COVID-19 in relation to age, sex and both clinical and biochemical severity. We carried out a prospective observational comparative cohort study enrolling 92 children (48 M, mean age 3.69 ± 5.1 years) with acute SARS-CoV-2 infection and 7 with MIS-C along with 41 age- and sex-matched controls. Sera collected at admission, acute phase, discharge and remission were analyzed by Gas Chromatography Mass Spectroscopy. Here we identify a distinct signature featuring inflammation, reactive oxygen species and glicerolipids pathways in children with acute SARS-CoV-2 infection compared to controls (permutation test p = 0.0015). Metabolomic profile changes are associated with age, disease status and disease severity, while a normalization of these changes is observed at disease resolution. MIS-C children showed a unique signature compared to age-/sex-matched COVID-19 patients or controls. Pediatric COVID-19 has a characteristic metabolomic signature featuring glucose and aminoacid metabolism, that varies with age and disease phenotype. Our study supports the value of metabolomics to unveil pathways related to host-viral interaction that may also help identify early predictors of disease evolution. Lo Vecchio, Discepolo et al., characterize the serum metabolomic profiles of children with acute SARS-CoV-2 infection and multisystem inflammatory syndrome (MIS-C). Distinct metabolic signatures involving inflammation, oxidative stress, and lipid metabolism correlate with age and disease severity, associate with MIS-C as a unique metabolic phenotype and reverse upon recovery. After the COVID-19 pandemic, despite the wide-spread vaccination campaigns, we have been witnessing multiple surges of SARS-CoV-2 epidemics around the globe that, albeit less severe, are still contributing significantly to morbidity in the general population. Children are frequently affected, and in rare cases may develop a complication known as Multisystem Inflammatory Syndrome that may have a critical course. In this study we have investigated changes in blood metabolites resulting from the interaction between the SARS-CoV-2 and children, revealing that their variations are associated with age and disease severity. Our study could help identifying early markers that may predict disease evolution.