Nehar-Belaid Djamel, Mejías Asunción, Xu Zhaohui, Marches Radu, Yerrabelli Rushil, Chen Guo, Mertz Sara, Ye Fang, Sánchez Pablo J, Tsang John S, Aydillo Teresa, Miorin Lisa, Cupic Anastasija, García-Sastre Adolfo, Ucar Duygu, Banchereau Jacques F, Pascual Virginia, Ramilo Octavio
The Jackson Laboratory for Genomic Medicine, Farmington, CT, 06032, USA.
Department of Pediatrics, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH, USA.
Nat Commun. 2025 May 16;16(1):4562. doi: 10.1038/s41467-025-59411-z.
Differences in immune profiles of children and adults with COVID-19 have been previously described. However, no systematic studies have been reported from infants hospitalized with severe disease. We applied a multidimensional approach to decipher the immune responses of SARS-CoV-2 infected infants (n = 26; 10 subacute, 11 moderate and 5 severe disease; median age = 1.6 months) and matched controls (n = 14; median age = 2 months). Single cell (scRNA-seq) profiling of PBMCs revealed substantial alterations in cell composition in SARS-CoV-2 infected infants; with most cell-types switching to an interferon-stimulated gene (ISG) state including: (i) CD14 monocytes co-expressing ISGs and inflammasome-related molecules, (ii) ISG naive CD4 T cells, (iii) ISG proliferating cytotoxic CD8 T cells, and (iv) ISG naive and transitional B cells. We observe increased serum concentrations of both interferons and inflammatory cytokines in infected infants. Antibody responses to SARS-CoV-2 are also consistently detected in the absence of anti-IFN autoantibodies. Compared with infected adults, infants display a similar ISG signature in monocytes but a markedly enhanced ISG signature in T and B cells. These findings provide insights into the distinct immune responses to SARS-CoV-2 in the first year of life and underscore the importance of further defining the unique features of early life immunity.
此前已有关于新冠病毒感染儿童和成人免疫特征差异的描述。然而，尚未有针对重症住院婴儿的系统性研究报告。我们采用多维度方法来解读感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的婴儿（n = 26；10例亚急性期、11例中度和5例重症；中位年龄 = 1.6个月）及匹配对照组（n = 14；中位年龄 = 2个月）的免疫反应。外周血单核细胞（PBMC）的单细胞（scRNA-seq）分析显示，SARS-CoV-2感染婴儿的细胞组成有显著改变；大多数细胞类型转变为干扰素刺激基因（ISG）状态，包括：（i）共表达ISG和炎性小体相关分子的CD14单核细胞，（ii）ISG未成熟CD4 T细胞，（iii）ISG增殖性细胞毒性CD8 T细胞，以及（iv）ISG未成熟和过渡性B细胞。我们观察到感染婴儿血清中干扰素和炎性细胞因子的浓度均升高。在没有抗干扰素自身抗体的情况下，也持续检测到对SARS-CoV-2的抗体反应。与感染成人相比，婴儿单核细胞中的ISG特征相似，但T细胞和B细胞中的ISG特征明显增强。这些发现为生命第一年对SARS-CoV-2的独特免疫反应提供了见解，并强调了进一步明确早期生命免疫独特特征的重要性。
