Advancing pediatric critical care: Sepsis, immune dysregulation, and precision therapies

Pediatric critical care remains a pivotal frontier in modern medicine, confronting unique challenges shaped by the dynamic physiology and developmental vulnerabilities of children. Sepsis, a leading cause of morbidity and mortality in pediatric intensive care units (PICUs), accounts for over 20% of global childhood deaths, yet age-specific diagnostic criteria and therapies remain underdeveloped. Emerging evidence highlights the distinct immune dysregulation patterns in pediatric sepsis compared to adults, necessitating tailored therapeutic strategies. Despite advancements in supportive therapies, the underlying pathophysiology of sepsis-induced hyperinflammation, immune paralysis, and organ crosstalk remains poorly understood, particularly in developing organ systems. Emerging evidence suggests that dysregulated immune responses—ranging from cytokine storms to immunosuppressive states—drive heterogeneous clinical trajectories, complicating risk stratification and targeted interventions. Furthermore, the interplay between sepsis, multi-organ failure (MOF), and chronic critical illness in children is underexplored, hindering the development of precision therapies. This Research Topic seeks to dissect these complexities by integrating novel biomarkers, omics-driven insights, and innovative therapeutic strategies tailored to the unique needs of critically ill children.

This Research Topic aims to consolidate cutting-edge research on the mechanisms, prediction, and management of life-threatening conditions in pediatric critical care, with a focus on sepsis, MOF, and immune dysregulation. We seek to bridge critical knowledge gaps in understanding age-specific inflammatory pathways, organ cross-talk, and long-term outcomes while fostering multidisciplinary collaborations to translate mechanistic discoveries into clinically actionable solutions. By highlighting pediatric-specific data, this collection will challenge current paradigms and accelerate the development of precision medicine approaches to improve survival and functional recovery.

We invite original research, reviews, and clinical trials addressing, but not limited to, the following themes:

• Molecular mechanisms of sepsis-induced immune dysregulation (e.g., NLRP3 inflammasome activity, T-cell exhaustion) in pediatric populations.

• Biomarkers and multi-omics signatures for early prediction of sepsis progression or MOF.

• Age-stratified immunomodulatory therapies (e.g., IFN-γ, IL-7, or corticosteroid protocols).

• Organ-specific crosstalk in MOF: gut-lung axis, endothelial dysfunction, or mitochondrial failure.

• Long-term neurodevelopmental, metabolic, or immunological outcomes post-critical illness.

• Novel technologies: AI-driven risk models, extracorporeal immunoadsorption, or single-cell profiling in pediatric sepsis.

• Ethical considerations in end-of-life care and resource allocation for refractory MOF.

• Translational studies bridging preclinical models (e.g., age-specific murine systems) to clinical trials.

Submissions must emphasize pediatric-specific data and avoid extrapolations from adult cohorts without validation. Interdisciplinary studies integrating immunology, critical care, and systems biology are strongly encouraged.