National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Rd, Beijing 102206, China.
Fujian Provincial Key Laboratory of Zoonosis Research (Fujian Center for Disease Control and Prevention); The Practice Base on the School of Public Health, Fujian Medical University, Fuzhou, Fujian 350011, China.
J Infect. 2024 Feb;88(2):158-166. doi: 10.1016/j.jinf.2023.12.003. Epub 2023 Dec 13.
The symptoms of children infected with SARS-CoV-2 are mainly asymptomatic, mild, moderate, and a few severe cases. To understand the immune response characteristics of children infected with SARS-COV-2 who do not develop severe cases, 82 children infected with the SARS-CoV-2 delta strain were recruited in this study. Our results showed that high levels of IgG, IgM, and neutralization antibodies appeared in children infected with SARS-CoV-2. SARS-CoV-2 induced upregulation of both pro-inflammatory factors including TNF-α and anti-inflammatory factors including IL-4 and IL-13 in the children, even IL-10. The expression of INF-α in infected children also showed a significant increase compared to healthy children. However, IL-6, one of the important inflammatory factors, did not show an increase in infected children. It is worth noting that a large number of chemokines reduced in the SARS-CoV-2-infected children. Subsequently, TCR Repertoire, TCRβ bias, and preferential usage were analyzed on data of TCR next-generation sequencing from 8 SARS-CoV-2-infected children and 8 healthy controls. We found a significant decrease in TCR clonal diversity and a significant increase in TCR clonal expansion in SARS-CoV-2-infected children compared to healthy children. The most frequent V and J genes in SARS-CoV-2 children were TRBV28 and TRBJ2-1. The most frequently VβJ gene pairing in SARS-CoV-2 infected children was TRBV20-1-TRBJ2-1. The strong antiviral antibody levels, low expression of key pro-inflammatory factors, significant elevation of anti-inflammatory factors, and downregulation of many chemokines jointly determine that SARS-CoV-2-infected children rarely develop severe cases. Overall, our findings shed a light on the immune response of non-severe children infected with SARS-CoV-2.
儿童感染 SARS-CoV-2 的症状主要为无症状、轻症、中症,少数为重症。为了了解不发展为重症的儿童感染 SARS-CoV-2 的免疫应答特征,本研究招募了 82 名感染 SARS-CoV-2 德尔塔株的儿童。我们的结果表明,儿童感染 SARS-CoV-2 后会出现高水平的 IgG、IgM 和中和抗体。SARS-CoV-2 诱导儿童体内促炎因子(包括 TNF-α)和抗炎因子(包括 IL-4 和 IL-13,甚至 IL-10)的上调。与健康儿童相比,感染儿童 IFN-α的表达也显著增加。然而,作为重要炎症因子之一的 IL-6 在感染儿童中并没有增加。值得注意的是,大量趋化因子在 SARS-CoV-2 感染儿童中减少。随后,我们对 8 名 SARS-CoV-2 感染儿童和 8 名健康对照的 TCR 下一代测序数据进行 TCR repertoire、TCRβ偏向和偏好性使用分析。与健康儿童相比,我们发现 SARS-CoV-2 感染儿童的 TCR 克隆多样性显著降低,TCR 克隆扩增显著增加。SARS-CoV-2 儿童中最常见的 V 和 J 基因是 TRBV28 和 TRBJ2-1。SARS-CoV-2 感染儿童中最常见的 VβJ 基因配对是 TRBV20-1-TRBJ2-1。强烈的抗病毒抗体水平、关键促炎因子表达水平低、抗炎因子显著升高以及许多趋化因子下调共同决定了 SARS-CoV-2 感染儿童很少发展为重症。总之,我们的研究结果阐明了非重症 SARS-CoV-2 感染儿童的免疫应答特征。