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.

Backgrounds:

Before the COVID-19 pandemic, we described an increase in tuberculosis (TB) notification rates at the Campania Region’s paediatric Reference Centre (CRRC). Since 2020, we observed a reduction in the incidence of TB, hence, we decided to compare TB incidence rates and disease severity in the period 2020-2021 to 2011-2019.

Methods

We conducted a prospective cohort study (Jan 1st 2011 to Dec 31st 2021) enrolling children <18 years who received diagnosis of TB at the CRRC. Yearly TB incidence rates were calculated dividing the number of new cases with the number of residents < 18 years in Campania. Disease severity was based on the need of oxygen support and the score proposed by Wiseman et al. according to localization (pulmonary and extrapulmonary) and/or cavitation.

Results:

Overall 154 children (48.1% male, median age 63 months, IQR 101.76) received diagnosis of TB, 142 in the period 2011-2019 with a significant increase in notification rates overtime (Fig). In 2020-2021, 12 new diagnoses were notified with a drop from 1.46/100.000 (95%CI, 0.84-2.37) in 2019 to 0.38 (95%CI, 0.1-0.96) in 2021. Two (17%) needed oxygen support. The number of cases classified as severe according to clinical score, was higher in the period 2020-2021 (5/12, 42%) compared with 2011-2019 (22/142, 15%), with 2/12 (17%) extrapulmonary and 2/12 (17%) cavitation.

Conclusions/Learning Points:

During 2020-2021 the CRRC registered a decrease in TB notification rates and an increase in the severity of the disease, compared with 2011-2019. The Stop TB Partnership suggested that COVID-19 could cause an excess of TB cases globally between 2020 and 2025. That rebound, in Campania, has not yet occurred likely because of the shift in medical attention from TB and the reallocation of human resources towards the pandemic effort.