Severe pediatric COVID‑19:a review from the clinical and immunopathophysiological perspectives

Background Coronavirus disease 2019(COVID-19)tends to have mild presentations in children.However,severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times,meriting further attention from clinicians.Meanwhile,the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood.Data sources A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed,Embase,and Wanfang databases.Searched keywords included“COVID-19 in children”,“severe pediatric COVID-19”,and“critical illness in children with COVID-19”.Results Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status.Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations,while various forms of cardiovascular and neurological involvement may also be seen.Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways,whose dysregulation in severe and critical diseases translates into adverse clinical manifestations.Multisystem inflammatory syndrome in children(MIS-C),a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure,denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity.Despite the considerable dissimilarities between the pediatric and adult immune systems,clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines.Conclusions Severe pediatric COVID-19 can affect multiple organ systems.The dysregulated immune pathways in severe COVID-19 shape the disease course,epitomize the vast functional diversity of the pediatric immune system and highlight the immunophenotypical differences between children and adults.Consequently,further research may be warranted to adequately address them in pediatric-specific clinical practice guidelines.

Autoimmmune hepatitis

Autoimmune hepatitis(AIH)is a T-cell mediated,inflammatory liver disease affecting all ages and characterized by female preponderance,elevated serum transaminase and immunoglobulin G levels,positive circulating autoantibodies,and presence of interface hepatitis at liver histology.AIH type 1,affecting both adults and children,is defined by positive anti-nuclear and/or antismooth muscle antibodies,while type 2 AIH,affecting mostly children,is defined by positive anti-liver-kidney microsomal type 1 and/or anti-liver cytosol type 1 antibody.While the autoantigens of type 2 AIH are well defined,being the cytochrome P4502D6(CYP2D6)and the formiminotransferase cyclodeaminase(FTCD),in type 1 AIH they remain to be identified.AIH-1 predisposition is conferred by possession of the MHC class II HLA DRB1*03 at all ages,while DRB1*04 predisposes to late onset disease;AIH-2 is associated with possession of DRB1*07 and DRB1*03.The majority of patients responds well to standard immunosuppressive treatment,based on steroid and azathioprine;second-and third-line drugs should be considered in case of intolerance or insufficient response.This review offers a comprehensive overview of pathophysiological and clinical aspects of AIH.