新型冠状病毒感染相关儿童多系统炎症综合征的病例对照研究

Multisystem inflammatory syndrome in children associated with novel coronavirus infection:A case-control study

背景儿童多系统炎症综合征(MIS-C)与新型冠状病毒(SARS-CoV-2)感染相关,既往文献研究多为病例报告或综述,难治性MIS-C仅为个案报告。目的探讨难治性MIS-C与非难治性MIS-C的区别,提高对MIS-C的疾病认识。设计病例对照研究。方法收集浙江地区6家医院的MIS-C连续病例,将一线治疗后持续发热和/或终末器官受累定义为难治性MIS-C(病例组),余为非难治性MIS-C(对照组),总结两组患儿的基本信息、临床表现、实验室检查、影像学检查、治疗药物及疗效等临床资料,并行单因素分析。主要结局指标MIS-C临床特征。结果23例MIS-C患儿进入本文分析,发病年龄(4.8±3.4)岁,SARS-CoV-2感染或接触史与诊断MIS-C间隔时间(30±9)d。病例组4例,男女各2例;对照组19例,男10例,女9例。两组基本信息、临床表现和严重并发症[颅内出血、巨噬细胞活化综合征(MAS)、冠脉扩张、脑炎]差异均无统计学意义。影像学表现中,病例组≥2个浆膜腔受累(75%vs 16%)比例和心包积液(75%vs 11%)比例均高于对照组;实验室检查中,病例组PLT计数低于对照,PCT、D-二聚体、IL-6、IL-10和INF-γ均高于对照组;差异均有统计学意义。对照组单用IVIG治疗8例(42%),单用糖皮质激素治疗4例(21%),IVIG+糖皮质激素治疗6例(32%),病例组4例在糖皮质激素+IVIG二联用药加用托珠单抗治疗。23例均好转出院,无死亡病例。对照组1例并发严重颅内出血患儿,出院时、6月随访时遗留偏瘫,6月后失访;1例并发冠脉扩张患儿出院后1个月随访时恢复正常。结论MIS-C可导致颅内出血、MAS、冠脉扩张等严重并发症,预后相对较好,难治性MIS-C患儿炎症反应更重,多系统受累更明显,托珠单抗治疗有效。

Background Multisystem inflammatory syndrome in children(MIS-C)is associated with SARS-CoV-2 infection.Most previous studies on MIS-C are case reports or reviews,with refractory MIS-C only documented in individual case reports.Objective To explore the differences between refractory MIS-C and non-refractory MIS-C and to enhance understanding of the disease.Design Case-control study.Methods Consecutive cases of MIS-C from six hospitals in Zhejiang Province were collected.Refractory MIS-C was defined as persistent fever and/or terminal organ involvement after first-line treatment(case group),while the remaining cases were classified as non-refractory MIS-C(control group).The basic information,clinical manifestations,laboratory tests,imaging findings,treatment,and efficacy of the two groups were summarized and analyzed using univariate analysis.Main outcome measures Clinical characteristics of MIS-C.Results A total of 23 children with MIS-C were included in this analysis,with an average onset age of 4.8±3.4 years.The interval between SARS-CoV-2 infection or exposure and MIS-C diagnosis was 30±9 days.The case group included 4 children(2 males and 2 females),while the control group included 19 children(10 males and 9 females).There were no statistically significant differences between the two groups in terms of basic information,clinical manifestations,or severe complications.In imaging findings,the case group had higher proportions of involvement in≥2 serous cavities(75%vs.16%)and pericardial effusion(75%vs.11%)compared to the control group.In laboratory tests,the case group showed lower platelet(PLT)counts,higher procalcitonin(PCT),and D-dimer levels,as well as elevated levels of IL-6,IL-10,and IFN-γ,all of which were statistically significant.In the control group,8 cases(42%)were treated with IVIG alone,4 cases(21%)with corticosteroids alone,and 6 cases(32%)with a combination of IVIG and corticosteroids.In the case group,all 4 children received additional tocilizumab treatment on top of corticosteroids and IVIG.All 23 children improved and were discharged,with no fatalities.One child in the control group experienced severe intracranial hemorrhage and was left with hemiplegia at discharge and during a 6-month follow-up,but was lost to follow-up thereafter.Another child with coronary artery dilation returned to normal after 1 month of post-discharge follow-up.Conclusion MIS-C can lead to severe complications such as intracranial hemorrhage,macrophage activation syndrome(MAS),and coronary artery dilation,but generally has a relatively good prognosis.Children with refractory MIS-C exhibit more intense inflammatory responses and more significant multisystem involvement.Tocilizumab is effective in treatment.