Multisystem inflammatory syndrome associated with the SARS-CoV-2 pandemic has recently been described in children (MIS-C), partially overlapping with Kawasaki disease (KD). We hypothesized that (a) MIS-C and prepandemic KD cytokine profiles may be unique and justify the clinical differences observed, and (b) SARS-CoV-2–specific immune complexes (ICs) may explain the immunopathology of MIS-C. Seventy-four children were included: 14 with MIS-C, 9 patients positive for SARS-CoV-2 by PCR without MIS-C (COVID), 14 with prepandemic KD, and 37 healthy controls (HCs). Thirty-four circulating cytokines were quantified in pretreatment serum or plasma samples and the presence of circulating SARS-CoV-2 ICs was evaluated in MIS-C patients. Compared with HCs, the MIS-C and KD groups showed most cytokines to be significantly elevated, with IFN-γ–induced response markers (including IFN-γ, IL-18, and IP-10) and inflammatory monocyte activation markers (including MCP-1, IL-1α, and IL-1RA) being the main triggers of inflammation. In linear discriminant analysis, MIS-C and KD profiles overlapped; however, a subgroup of MIS-C patients (MIS-C^plus) differentiated from the remaining MIS-C patients in IFN-γ, IL-18, GM-CSF, RANTES, IP-10, IL-1α, and SDF-1 and incipient signs of macrophage activation syndrome. Circulating SARS-CoV-2 ICs were not detected in MIS-C patients. Our findings suggest a major role for IFN-γ in the pathogenesis of MIS-C, which may be relevant for therapeutic management.

Background: Congenital cytomegalovirus (cCMV) infection is the most frequent mother-to-child transmitted infection worldwide and a prevalent cause of neonatal disease and long-term morbidity. The kidney is a target organ for CMV, which replicates in renal tubules and is excreted in large quantities in urine for years in children with cCMV infection. Nonetheless, kidney disease has rarely been reported in cCMV-infected patients. Objective: We aimed to describe the available data on renal involvement in patients with cCMV infection at the pathologic, functional, anatomical, and/or clinical levels. Methods: A systematic search was performed in the MEDLINE/PubMed, SCOPUS, and Cochrane databases. Studies describing any renal involvement in fetuses or neonates aged ≤3 weeks at diagnosis of microbiologically confirmed cCMV infection were eligible. Results: Twenty-four articles were included, with a very low level of evidence. Pathologic findings in autopsy studies universally described CMV typical inclusion bodies in tubular cells. No functional studies were identified. cCMV infection was not associated with an increased risk of kidney malformations. Congenital nephrotic syndrome was the most common clinical condition associated with cCMV, but a causal relationship cannot be established. Conclusions: Typical pathological features of cCMV infection are very common in renal tissue, but they do not seem to entail significant consequences at the anatomical or clinical levels.

The effectiveness of antimicrobial stewardship programs (ASP) in reducing antimicrobial use (AU) in children has been proved. Many interventions have been described suitable for different institution sizes, priorities, and patients, with surgical wards being one of the areas that may benefit the most. We aimed to describe the results on AU and length of stay (LOS) in a pre-post study during the three years before (2014–2016) and the three years after (2017–2019) implementation of an ASP based on postprescription review with feedback in children and adolescents admitted for appendix-related intraabdominal infections (AR-IAI) in a European Referral Paediatric University Hospital. In the postintervention period, the quality of prescriptions (QP) was also evaluated. Overall, 2021 AR-IAIs admissions were included. Global AU, measured both as days of therapy/100 patient days (DOT/100PD) and length of therapy (LOT), and global LOS remained unchanged in the postintervention period. Phlegmonous appendicitis LOS (p = 0.003) and LOT (p < 0.001) significantly decreased, but not those of other AR-IAI diagnoses. The use of piperacillin–tazobactam decreased by 96% (p = 0.044), with no rebound in the use of other Gram-negative broad-spectrum antimicrobials. A quasisignificant (p = 0.052) increase in QP was observed upon ASP implementation. Readmission and case fatality rates remained stable. ASP interventions were safe, and they reduced LOS and LOT of phlegmonous appendicitis and the use of selected broad-spectrum antimicrobials, while increasing QP in children with AR-IAI.