Role of interleukin 6 polymorphism and inflammatory markers in outcome of pediatric Covid- 19 patients
Authors: AbdelAziz Reem A. , Abd-Allah Samir Tamer , Moness Hend M. , Anwar Ahmed M. , Mohamed Zamzam Hassan 
Published: October 2024

Abstract
Background
IL-6 polymorphisms were associated to viral infection outcomes through affection of IL-6 production and it is an early indicator of tissue injury and systemic inflammatory response. The study aimed to determine whether genetic IL-6 polymorphisms, serum interleukin-6 level and inflammatory markers (Presepsin, CXCL-10, C3, and C4) are associated with the prediction of disease severity in pediatric COVID-19 patients and its possible use as a prognostic tool in pediatric patients admitted to hospital.

Methods
This prospective cohort study was conducted on 150 children with COVID-19. Patients were divided according to the severity of infection into four groups: group I (mild) 67 cases; group II (moderate) 53 cases, group III (severe) 17 cases and group IV (critical) 14 cases. Serum Interleukin 6, CXCL-10, Presepsin, renal and liver functions, electrolytes, C3, C4, ferritin, and D dimer serum levels were assessed in all patients. The Kruskal Wallis test used to compare parametric quantitative data between studied groups and Mann Whitney test for each pair of groups. Non-parametric quantitative data was compared between studied groups using a one-way ANOVA test and post-hoc Bonferroni analysis for each pair of groups.

Results
Group I: 35 males and 32 females with a median age of 16 months. Group II: 17 males and 35 females with a median age of 13 months. Group III: 6 males and 11 females with a median age of 12 months and group IV: 3 males and 11 females with a median age of 12 months. There was no statistical difference between the studied groups regarding gender and age. Serum levels of IL- 6, serum ferritin; D-dimer, Presepsin and CXCL 10 were significantly higher in both severe and critical groups than the other 2 groups (mild and moderate). ROC curve analysis showed that interleukin-6 and Presepsin were good markers for prediction of severity of COVID-19 among the diseased children. For severe cases, the sensitivity of interleukin-6 was 76.47% and specificity was 92.31%. For critical cases, the sensitivity of interleukin-6 was 71.43% and specificity was 82.35%. The sensitivity of Presepsin was 76.47% and specificity was 88.46% in severe cases. For critical cases, the sensitivity of Presepsin was 78.57% and specificity of 91.2%. There was significant difference in IL-6 572 allelic among moderate cases with the most frequent 42.3% for genotype (GC) and allelic among severe cases with the most frequent 47.1% for genotype (GC). Significant difference in IL-6 174 allelic among critical cases with the most frequent 78.6% for genotype (CC).

Conclusions
Children whom expressed GC genotypes of IL6 (-572G > C) polymorphism are at a considerably higher risk of developing a severe disease. This risk is significantly larger in the severe group of children than in children in critical condition who have GC genotypes of IL6 (-174 G > C) polymorphism. While IL6 (-597G > A) polymorphism has no role in COVID 19 severity in children.