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.
Vecchio et al. (Fri,) studied this question.