多系统炎症综合征和2019冠状病毒病患儿的血清学及细胞因子特征
Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019.
作者信息
Lapp Stacey A, Abrams Joseph, Lu Austin T, Hussaini Laila, Kao Carol M, Hunstad David A, Rosenberg Robert B, Zafferani Marc J, Ede Kaleo C, Ballan Wassim, Laham Federico R, Beltran Yajira, Hsiao Hui-Mien, Sherry Whitney, Jenkins Elan, Jones Kaitlin, Horner Anna, Brooks Alyssa, Bryant Bobbi, Meng Lu, Hammett Teresa A, Oster Matthew E, Bamrah-Morris Sapna, Godfred-Cato Shana, Belay Ermias, Chahroudi Ann, Anderson Evan J, Jaggi Preeti, Rostad Christina A
机构信息
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
出版信息
Open Forum Infect Dis. 2022 Feb 24;9(3):ofac070. doi: 10.1093/ofid/ofac070. eCollection 2022 Mar.
BACKGROUND
The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.
METHODS
We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients.
RESULTS
Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17-9.23]).
CONCLUSIONS
MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.
背景
多系统炎症综合征（MIS-C）患儿与2019冠状病毒病（COVID-19）患儿的血清学和细胞因子反应尚不清楚。
方法
我们对符合美国疾病控制与预防中心MIS-C病例定义（n = 118）、急性COVID-19（n = 88）或同期健康对照（n = 24）的住院儿童进行了一项前瞻性、多中心横断面研究。我们测量了患者体内严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突受体结合域（RBD）免疫球蛋白G（IgG）滴度和细胞因子浓度，并进行多变量分析以确定与MIS-C相关的细胞因子特征。我们还在部分患者亚组中测量了核衣壳IgG和恢复期RBD IgG。
结果
MIS-C患儿的SARS-CoV-2 RBD IgG显著高于急性COVID-19患儿（中位数，2783对146；P <.001），且滴度与核衣壳IgG相关。对于MIS-C患者，恢复期RBD IgG滴度下降（中位数，2783对1135；P = 0.010），而COVID-19患者则相反（中位数，146对4795；P <.001）。MIS-C的特征是短暂的急性促炎性高细胞因子血症，包括白细胞介素（IL）-6、IL-10、IL-17A和干扰素γ（IFN-γ）水平升高。这些细胞因子中至少3种升高与住院时间延长≥8天的患病率显著增加相关（患病率比值，3.29 [95%可信区间，1.17 - 9.23]）。
结论
MIS-C与高滴度的SARS-CoV-2 RBD IgG抗体以及IL-6、IL-10、IL-17A和IFN-γ引起的急性高细胞因子血症相关。
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