Backgrounds:

Metabolomic alterations have been identified in adults with SARS-CoV-2 infection, however this approach has not been used in children so far. Children usually have a mild course, although a small percentage may develop severe disease or Multisystem Inflammatory Syndrome (MIS-C).

Methods

We carried out a prospective comparative cohort study (April 2020 to June 2021) enrolling children referred to our COVID-center for symptoms related to acute SARS-CoV-2 infection (positive nasopharyngeal swab) or MIS-C and a cohort of age- and sex-matched children who served as controls. Metabolomic analysis was performed by Gas Chromatography Mass Spectroscopy approach using blood samples collected at admission, acute phase, discharge and a follow-up visit scheduled after negativization. All enrolled patients were hospitalized and classified into mild-to-moderate or severe COVID-19 according to clinical, radiological, and biochemical features.

Results:

A specific metabolomic signature was identified in 92 children (48 males, mean age 3.69±5.1 years) with acute SARS-CoV-2 infection, compared to 41 controls (permutation test statistic p=0.0015, Figure) involving specific pathways, such as: inflammation (spermidine and hypoxanthine), reactive oxygen species pathway (riboflavin) and glicerolipids pathways.

Distinct metabolic signatures were significantly associated with child’s age (mainly > 3 years), clinical and biochemical severity and timing from SARS-CoV-2 infection.

Children with MIS-C (n=9) showed a unique metabolomic signature and different from age- and sex-matched SARS-CoV-2-infected patients or controls characterized by an alteration of spermidine and sphingolipids.

Conclusions/Learning Points:

Pediatric SARS-CoV-2 infection has a characteristic metabolomic signature suggesting a possible involvement of intestinal microbiome, that varies according to patients’ age and disease phenotype. Metabolomic approach may be a useful tool to identify possible early markers of disease and predictors of severe diseases evolution or multi-system inflammatory syndrome.