Diaz Franco, Bustos B Raúl, Yagnam Felipe, Karsies Todd J, Vásquez-Hoyos Pablo, Jaramillo-Bustamante Juan-Camilo, Gonzalez-Dambrauskas Sebastián, Drago Michelle, Cruces Pablo
Unidad de Paciente Crítico Pediátrico, Hospital El Carmen de Maipú, Santiago, Chile.
Escuela de Medicina, Universidad Finis Terrae, Santiago, Chile.
Front Pediatr. 2021 Nov 15;9:756083. doi: 10.3389/fped.2021.756083. eCollection 2021.
Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection is thought to be driven by a post-viral dysregulated immune response, where interleukin 6 (IL-6) might have a central role. In this setting, IL-6 inhibitors are prescribed as immunomodulation in cases refractory to standard therapy. To compare plasma IL-6 concentration between critically ill children with MIS-C and sepsis. A retrospective cohort study from previously collected data. Individual patient data were gathered from three different international datasets. Critically ill children between 1 month-old and 18 years old, with an IL-6 level measured within 48 h of admission to intensive care. Septic patients were diagnosed according to Surviving Sepsis Campaign definition and MIS-C cases by CDC criteria. We excluded children with immunodeficiency or immunosuppressive therapy. None. The primary outcome was IL-6 plasma concentration in MIS-C and sepsis group at admission to the intensive care unit. We described demographics, inflammatory biomarkers, and clinical outcomes for both groups. A subgroup analysis for shock in each group was done. We analyzed 66 patients with MIS-C and 44 patients with sepsis. MIS-C cases were older [96 (48, 144) vs. 20 (5, 132) months old, < 0.01], but no differences in sex (41 vs. 43% female, = 0.8) compared to septic group. Mechanical ventilation use was 48.5 vs. 93% ( < 0.001), vasoactive drug use 79 vs. 66% ( = 0.13), and mortality 4.6 vs. 34.1% ( < 0.01) in MIS-C group compared to sepsis. IL-6 was 156 (36, 579) ng/dl in MIS-C and 1,432 (122, 6,886) ng/dl in sepsis ( < 0.01), while no significant differences were observed in procalcitonin (PCT) and c-reactive protein (CRP). 52/66 (78.8%) patients had shock in MIS-C group, and 29/44 (65.9%) had septic shock in sepsis group. Septic shock had a significantly higher plasma IL-6 concentration than the three other sub-groups. Differences in IL-6, CRP, and PCT were not statistically different between MIS-C with and without shock. IL-6 plasma concentration was elevated in critically ill MIS-C patients but at levels much lower than those of sepsis. Furthermore, IL-6 levels don't discriminate between MIS-C cases with and without shock. These results lead us to question the role of IL-6 in the pathobiology of MIS-C, its diagnosis, clinical outcomes, and, more importantly, the off-label use of IL-6 inhibitors for these cases.
与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染相关的儿童多系统炎症综合征（MIS-C）被认为是由病毒后免疫反应失调驱动的，其中白细胞介素6（IL-6）可能起核心作用。在这种情况下，IL-6抑制剂被用作标准治疗难治性病例的免疫调节药物。为比较重症MIS-C患儿和脓毒症患儿的血浆IL-6浓度。一项基于先前收集数据的回顾性队列研究。从三个不同的国际数据集中收集个体患者数据。年龄在1个月至18岁之间的重症患儿，其IL-6水平在重症监护入院后48小时内测量。脓毒症患者根据拯救脓毒症运动定义进行诊断，MIS-C病例根据美国疾病控制与预防中心（CDC）标准诊断。我们排除了免疫缺陷或接受免疫抑制治疗的儿童。无。主要结局是重症监护病房入院时MIS-C组和脓毒症组的IL-6血浆浓度。我们描述了两组的人口统计学、炎症生物标志物和临床结局。对每组休克情况进行了亚组分析。我们分析了66例MIS-C患者和44例脓毒症患者。MIS-C病例年龄更大[96（48，144）个月对20（5，132）个月，P<0.01]，但与脓毒症组相比，性别无差异（女性分别为41%对43%，P = 0.8）。MIS-C组机械通气使用率为48.5%对93%（P<0.001），血管活性药物使用率为79%对66%（P = 0.13），死亡率为4.6%对34.1%（P<0.01）。MIS-C组IL-6为156（36，579）ng/dl，脓毒症组为1432（122，6886）ng/dl（P<0.01），而降钙素原（PCT）和C反应蛋白（CRP）无显著差异。MIS-C组52/66（78.8%）患者发生休克，脓毒症组29/44（65.9%）患者发生脓毒症休克。脓毒症休克患者的血浆IL-6浓度显著高于其他三个亚组。有休克和无休克的MIS-C患者在IL-6、CRP和PCT方面的差异无统计学意义。重症MIS-C患者的IL-6血浆浓度升高，但水平远低于脓毒症患者。此外，IL-6水平无法区分有休克和无休克的MIS-C病例。这些结果使我们质疑IL-6在MIS-C病理生物学、诊断、临床结局中的作用，更重要的是，质疑IL-6抑制剂在这些病例中的超说明书使用情况。
