Neutrophil Extracellular Traps in Pediatric Infections: A Systematic Review.

Abstract

<h4>Background</h4>Neutrophil extracellular traps (NETs) are granule- and nucleus-derived structures that support innate immunity. While the contribution of NETs to adult infections and autoimmune diseases is well studied, evidence in children is still inconsistent. This review aimed to summarize current findings on NETs in pediatric infections.<h4>Methods</h4>This study followed the Cochrane Handbook for Systematic Reviews of Interventions and adhered to the PRISMA guidelines. A search was conducted in major databases (MEDLINE/PubMed and Scopus) from inception until 5 September 2025. The study quality was evaluated using the modified Newcastle-Ottawa Scale.<h4>Results</h4>Eleven studies were included in the systematic review. In respiratory disease, the role of NETs was well described and their formation correlated with severity. Patients with febrile urinary tract infections showed elevated urinary NET-associated markers. In COVID-19 infection, NET levels were unchanged in uncomplicated cases but elevated in multisystem inflammatory syndrome in children. Findings in sepsis were inconsistent.<h4>Conclusions</h4>This systematic review presents the published evidence on NET formation in the pediatric population, assessing the current knowledge and identifying the gaps to guide research. Future studies should aim to standardize NET detection methods, evaluate their prognostic value in large prospective cohorts, and explore the various NET-associated mechanisms in children.