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白细胞介素6多态性和炎症标志物在儿童新冠病毒肺炎患者预后中的作用

Role of interleukin 6 polymorphism and inflammatory markers in outcome of pediatric Covid- 19 patients.

作者信息

AbdelAziz Reem A, Abd-Allah Samir Tamer, Moness Hend M, Anwar Ahmed M, Mohamed Zamzam Hassan

机构信息

Pediatric Department, Faculty of Medicine, Minia University, Minia, Egypt.

Clinical Pathology Department, Faculty of Medicine, Minia University, Minia, Egypt.

出版信息

BMC Pediatr. 2024 Oct 1;24(1):625. doi: 10.1186/s12887-024-05071-9.

DOI:10.1186/s12887-024-05071-9
PMID:39354444
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11443869/
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.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c9/11443869/191a5ca07808/12887_2024_5071_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c9/11443869/5be9742fea73/12887_2024_5071_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c9/11443869/191a5ca07808/12887_2024_5071_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c9/11443869/5be9742fea73/12887_2024_5071_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9c9/11443869/191a5ca07808/12887_2024_5071_Fig2_HTML.jpg
摘要

背景

白细胞介素-6(IL-6)基因多态性通过影响IL-6的产生与病毒感染结局相关,且它是组织损伤和全身炎症反应的早期指标。本研究旨在确定IL-6基因多态性、血清白细胞介素-6水平及炎症标志物(可溶性髓系细胞触发受体-1、CXC趋化因子配体10、补体C3和C4)是否与儿童新型冠状病毒肺炎(COVID-19)患者疾病严重程度的预测相关,以及其作为住院儿童患者预后工具的可能性。

方法

对150例COVID-19患儿进行了这项前瞻性队列研究。根据感染严重程度将患者分为四组:I组(轻度)67例;II组(中度)53例,III组(重度)17例,IV组(危重症)14例。对所有患者评估血清白细胞介素6、CXC趋化因子配体10、可溶性髓系细胞触发受体-1、肾肝功能、电解质、C3、C4、铁蛋白和D-二聚体血清水平。采用Kruskal Wallis检验比较研究组间的参数定量数据,每组间采用Mann Whitney检验。使用单因素方差分析比较研究组间的非参数定量数据,并对每组进行事后Bonferroni分析。

结果

I组:35例男性和32例女性,中位年龄16个月。II组:17例男性和35例女性,中位年龄13个月。III组:6例男性和11例女性,中位年龄12个月,IV组:3例男性和11例女性,中位年龄12个月。研究组间在性别和年龄方面无统计学差异。重度和危重症组的血清IL-6、血清铁蛋白、D-二聚体、可溶性髓系细胞触发受体-1和CXC趋化因子配体10水平均显著高于其他两组(轻度和中度)。ROC曲线分析表明,白细胞介素-6和可溶性髓系细胞触发受体-1是患病儿童中预测COVID-19严重程度的良好标志物。对于重症病例,白细胞介素-6的敏感性为76.47% , 特异性为92.31%。对于危重症病例,白细胞介素-6的敏感性为71.43% , 特异性为82.35%。可溶性髓系细胞触发受体-1在重症病例中的敏感性为76.47% , 特异性为88.46%。对于危重症病例,可溶性髓系细胞触发受体-1的敏感性为78.57% , 特异性为91.2%。中度病例中IL-6 572等位基因存在显著差异,基因型(GC)最常见,占42.3%;重度病例中IL-6等位基因存在显著差异,基因型(GC)最常见,占47.1%。危重症病例中IL-6 174等位基因存在显著差异,基因型(CC)最常见,占78.6%。

结论

携带IL6(-572G>C)多态性GC基因型的儿童患重症疾病的风险显著更高。重度组儿童的这种风险明显高于携带IL6(-174 G>C)多态性GC基因型的危重症儿童。而IL6(-597G>A)多态性在儿童COVID-19严重程度中不起作用。

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