Division of Pediatric Infectious Diseases, Children's National Hospital, Washington, DC; Division of Cardiology, Children's National Hospital, Washington, DC; Department of Pediatrics, Immunology and Tropical Medicine, Washington, DC; Department of Microbiology, Immunology and Tropical Medicine, Washington, DC.
Division of Cardiology, Children's National Hospital, Washington, DC; Department of Pediatrics, Immunology and Tropical Medicine, Washington, DC.
J Pediatr. 2021 Oct;237:125-135.e18. doi: 10.1016/j.jpeds.2021.06.002. Epub 2021 Jun 25.
To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences.
We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls).
Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died.
This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.
评估区分儿童多系统炎症综合征（MIS-C）患者的人口统计学、临床和生物标志物特征；比较 MIS-C 亚型；确定细胞因子生物标志物；并描述病毒基因组序列。
我们对 2020 年 3 月至 9 月期间在华盛顿特区的一家四级独立儿童医院儿童国家（Children's National）根据机构 MIS-C 工作组方案住院治疗的 124 名患儿进行了前瞻性观察队列研究。在该队列中，63 名患儿被诊断为 MIS-C（39 例确诊，24 例可能），61 名患儿来自同一入院患儿队列，随后诊断为其他疾病（对照组）。
MIS-C 组和对照组的中位年龄和性别相似。黑人（46%）和拉丁裔（35%）患儿在 MIS-C 组中占比过高，黑人患儿风险最大（OR 4.62，95%CI 1.151-14.10；P=0.007）。患有 MIS-C 的危重症患儿更常出现心脏并发症（55% vs 28%；P=0.04），包括收缩性心肌功能障碍（39% vs 3%；P=0.001）和瓣膜反流（33% vs 7%；P=0.01）。MIS-C 病例的中位循环阈值为 31.8（27.95-35.1 IQR），显著高于（表明病毒载量较低）原发性严重急性呼吸综合征冠状病毒 2 感染。与对照组相比，细胞因子可溶性白细胞介素 2 受体、白细胞介素 [IL]-10 和 IL-6 在 MIS-C 患者中更高。细胞因子分析显示，危重症与非危重症（白细胞介素 2、可溶性白细胞介素 2 受体、IL-10、IL-6）、聚合酶链反应阳性与阴性（肿瘤坏死因子-α、IL-10、IL-6）以及存在与不存在心脏异常（白细胞介素-17）之间存在亚表型差异。病毒基因组序列的系统发生分析显示，起源于欧洲的 GH 分支占主导地位，MIS-C 患者与原发性冠状病毒病 19 患者相比没有差异。治疗耐受性良好，没有患儿死亡。
本研究建立了一个特征明确的大型 MIS-C 队列，该队列按照标准化方案进行评估和治疗，并确定了关键的临床、生物标志物、细胞因子、病毒载量和测序特征。长期随访将为 MIS-C 及其后遗症提供未来的见解。
