SARS-CoV-2-Specific T Cell Responses Are Stronger in Children With Multisystem Inflammatory Syndrome Compared to Children With Uncomplicated SARS-CoV-2 Infection.
SARS-CoV-2-Specific T Cell Responses Are Stronger in Children With Multisystem Inflammatory Syndrome Compared to Children With Uncomplicated SARS-CoV-2 Infection.
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DOI：
10.3389/fimmu.2021.793197
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发表时间：
2021
影响因子：
7.3
通讯作者：
Bollard CM
中科院分区：
文献类型：
--
作者：
Conway SR;Lazarski CA;Field NE;Jensen-Wachspress M;Lang H;Kankate V;Durkee-Shock J;Kinoshita H;Suslovic W;Webber K;Smith K;Cohen JI;Burbelo PD;Zhang A;Teach SJ;Ibeh T;Delaney M;DeBiasi RL;Keller MD;Bollard CM
尽管成人和儿童的感染率相似，但与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）相关的发病率和死亡率明显不同。与成人相比，儿童很少有严重的急性感染表现，但在感染后发生罕见且通常严重的儿童多系统炎症综合征（MIS-C）的风险很高。我们假设这些差异与成人和儿童之间SARS-CoV-2特异性T细胞（CST）反应的幅度和/或抗原特异性差异有关。因此，我们着手测量恢复期成人与儿童在SARS-CoV-2感染后有或无MIS-C的CST反应。从SARS-CoV-2感染后恢复期儿童和成人的血液中扩增CST，并通过细胞内流式细胞术、表面标记物和SARS-CoV-2特异性肽刺激后的细胞因子产生进行评估。使用荧光素酶免疫沉淀系统（LIPS）试验测定血清/血浆中是否存在加标抗体和核衣壳抗体。27例MIS-C患者中有26例，8例非MIS-C恢复期儿童中有7例，14例成人中有13例血清棘突和核衣壳抗体阳性。MIS-C患者的CST反应显著高于无并发症的SARS-CoV-2感染儿童，但弱于恢复期成人的CST反应。CST反应的幅度与疾病相关的差异表明，与成人无并发症感染后相比，儿童对SARS-CoV-2的感染后免疫力不同。尽管血清阳性率几乎一致，但患有MIS-C的儿童的CST反应比患有简单SARS-CoV-2感染的儿童更强，而比恢复期成年人更弱。
Despite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. We hypothesized that these differences in presentation are related to differences in the magnitude and/or antigen specificity of SARS-CoV-2-specific T cell (CST) responses between adults and children. We therefore set out to measure the CST response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection. CSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay. Twenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses in MIS-C patients were significantly higher than children with uncomplicated SARS-CoV-2 infection, but weaker than CST responses in convalescent adults. Age-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults post uncomplicated infection. Children with MIS-C have CST responses that are stronger than children with uncomplicated SARS-CoV-2 infection and weaker than convalescent adults, despite near uniform seropositivity.