Division of Neonatal and Pediatric Intensive Care, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva Switzerland.
J Pediatric Infect Dis Soc. 2021 Aug 14;10(6):706-713. doi: 10.1093/jpids/piaa142.
Recently, cases of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) have been reported worldwide. Negative polymerase chain reaction (RT-PCR) testing associated with positive serology in most of the cases suggests a postinfectious syndrome. Because the pathophysiology of this syndrome is still poorly understood, extensive virological and immunological investigations are needed.
We report a series of 4 pediatric patients admitted to Geneva University Hospitals with persistent fever and laboratory evidence of inflammation meeting the published definition of MIS-C related to COVID-19, to whom an extensive virological and immunological workup was performed.
RT-PCRs on multiple anatomical compartments were negative, whereas anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin A (IgA) and immunoglobulin G (IgG) were strongly positive by enzyme-linked immunosorbent assay and immunofluorescence. Both pseudoneutralization and full virus neutralization assays showed the presence of neutralizing antibodies in all children, confirming a recent infection with SARS-CoV-2. The analyses of cytokine profiles revealed an elevation in all cytokines, as reported in adults with severe COVID-19. Although differing in clinical presentation, some features of MIS-C show phenotypic overlap with hemophagocytic lymphohistiocytosis (HLH). In contrast to patients with primary HLH, our patients showed normal perforin expression and natural killer (NK) cell degranulation. The levels of soluble interleukin (IL)-2 receptor (sIL-2R) correlated with the severity of disease, reflecting recent T-cell activation.
Our findings suggest that MIS-C related to COVID-19 is caused by a postinfectious inflammatory syndrome associated with an elevation in all cytokines, and markers of recent T-cell activation (sIL-2R) occurring despite a strong and specific humoral response to SARS-CoV-2. Further functional and genetic analyses are essential to better understand the mechanisms of host-pathogen interactions.
最近，全球范围内有报道称与 2019 年冠状病毒病（COVID-19）相关的儿童多系统炎症综合征（MIS-C）病例。大多数情况下，聚合酶链反应（RT-PCR）检测为阴性，而血清学检测为阳性，这表明存在感染后综合征。由于该综合征的病理生理学仍知之甚少，因此需要进行广泛的病毒学和免疫学研究。
我们报告了日内瓦大学附属医院收治的 4 例符合 COVID-19 相关 MIS-C 发布定义的持续性发热和炎症实验室证据的儿科患者，对其进行了广泛的病毒学和免疫学检查。
多个解剖部位的 RT-PCR 检测均为阴性，而酶联免疫吸附试验和免疫荧光法检测抗严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）免疫球蛋白 A（IgA）和免疫球蛋白 G（IgG）均为强阳性。所有患儿的假中和和全病毒中和试验均显示存在中和抗体，证实了 SARS-CoV-2 的近期感染。细胞因子谱分析显示，所有患儿的细胞因子均升高，与成人重症 COVID-19 相似。虽然临床表现不同，但 MIS-C 的一些特征与噬血细胞性淋巴组织细胞增多症（HLH）有表型重叠。与原发性 HLH 患者不同，我们的患者表现出正常的穿孔素表达和自然杀伤（NK）细胞脱颗粒。可溶性白细胞介素（IL）-2 受体（sIL-2R）水平与疾病严重程度相关，反映了近期 T 细胞激活。
我们的研究结果表明，与 COVID-19 相关的 MIS-C 是由感染后炎症综合征引起的，伴有所有细胞因子升高，以及尽管对 SARS-CoV-2 有强烈和特异性的体液反应，但仍存在近期 T 细胞激活的标志物（sIL-2R）。进一步的功能和遗传分析对于更好地理解宿主-病原体相互作用的机制至关重要。
