Multisystem inflammatory syndrome in children (MIS-C) serum proteomics

While fewer cases of severe Coronavirus Disease 2019 (COVID-19) are reported globally in children, a small proportion of SARS-CoV-2 infected children develop a novel pediatric febrile entity called multisystem inflammatory syndrome in children (MIS-C) that develops 2 to 5 weeks after initial SARS-CoV-2 exposure. MIS-C primarily effects male children and children of Hispanic or black descent. MIS-C manifests as a severe and uncontrolled inflammatory response with multiorgan involvement. A hyperinflammatory state is evidenced by clinical makers of inflammation including high levels of C-reactive protein (CRP), ferritin, and D-dimers, and an increased expression of pro-inflammatory cytokines. Children often present with persistent fever, severe gastrointestinal symptoms, cardiovascular manifestations, respiratory symptoms and neurological symptoms6-11,13. Cardiovascular manifestations include hypotension, shock, cardiac dysfunction, myocarditis and pericardial effusion. In the united states, admission to the intensive care unit occurs in approximately 58% of cases. To understand disease pathogenesis of MIS-C and proteins associated with the severe form of disease we performed proteomics analysis of serum or plasma samples. We collected serum from healthy children (SARS-CoV-2 negative, n=20), mild MIS-C (non-ICU, n=5) and severe MIS-C (ICU, n = 20) patients. MIS-C definition and diagnosis was performed according to CDC guidelines. Healthy adult serum (n = 4) was also used for reference ranges quality control and we obtained plasma samples from Kawasaki Disease (KD; n=7) patients that were recruited before the Coronavirus Disease 2019 (COVID-19) pandemic.

全球范围内报告的儿童重症新型冠状病毒肺炎（Coronavirus Disease 2019, COVID-19）病例较少，但仍有小部分感染严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的儿童会出现一种新型儿童发热性病症——儿童多系统炎症综合征（Multisystem Inflammatory Syndrome in Children, MIS-C），该病症通常在初次暴露于SARS-CoV-2后2至5周发作。MIS-C主要累及男性儿童以及西班牙裔或黑人血统的儿童。其表现为伴随多器官受累的重度失控性炎症反应。高炎症状态可通过炎症临床标志物得以证实，包括C反应蛋白（C-reactive protein, CRP）、铁蛋白和D-二聚体水平升高，以及促炎细胞因子表达上调。患儿常表现为持续发热、重度胃肠道症状、心血管表现、呼吸道症状及神经系统症状6-11,13。心血管表现包括低血压、休克、心功能不全、心肌炎及心包积液。在美国，约58%的病例需要入住重症监护病房。为阐明MIS-C的发病机制以及与重症病例相关的蛋白，我们对血清或血浆样本开展了蛋白质组学分析。我们收集了健康儿童（SARS-CoV-2核酸阴性，n=20）、轻症MIS-C（非重症监护病房收治，n=5）及重症MIS-C（重症监护病房收治，n=20）患者的血清。MIS-C的定义与诊断遵循美国疾病控制与预防中心（Centers for Disease Control and Prevention, CDC）指南。我们还收集了4份健康成人血清用于参考范围质量控制，并获取了新型冠状病毒肺炎（COVID-19）大流行前招募的川崎病（Kawasaki Disease, KD）患者的血浆样本（n=7）。