Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Department of Hematology and Oncology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Front Immunol. 2024 Aug 1;15:1358725. doi: 10.3389/fimmu.2024.1358725. eCollection 2024.
The immunological characteristics that could protect children with coronavirus disease 2019 (COVID-19) from severe or fatal illnesses have not been fully understood yet.
Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on peripheral blood samples of 15 children (8 with COVID-19) and compared them to 18 adults (13 with COVID-19).
The child-adult integrated single cell data indicated that children with the disease presented a restrained response to type I interferon in most of the major immune cell types, along with suppression of upstream interferon regulatory factor and toll-like receptor expression in monocytes, which was confirmed by interferon stimulation assays. Unlike adult patients, children with COVID-19 showed lower frequencies of activated proinflammatory CD14+ monocytes, possibly explaining the rareness of cytokine storm in them. Notably, natural killer (NK) cells in pediatric patients displayed potent cytotoxicity with a rich expression of cytotoxic molecules and upregulated cytotoxic pathways, whereas the cellular senescence, along with the Notch signaling pathway, was significantly downregulated in NK cells, all suggesting more robust cytotoxicity in NK cells of children than adult patients that was further confirmed by CD107a degranulation assays. Lastly, a modest adaptive immune response was evident with more naïve T cells but less activated and proliferated T cells while less naïve B cells but more activated B cells in children over adult patients.
Conclusively, this preliminary study revealed distinct cell frequency and activation status of major immune cell types, particularly more robust NK cell cytotoxicity in PBMC that might help protect children from severe COVID-19.
保护儿童免受 2019 年冠状病毒病（COVID-19）严重或致命疾病影响的免疫特征尚未完全了解。
在这里，我们对 15 名儿童（8 名患有 COVID-19）的外周血样本进行了单细胞 RNA 测序（scRNA-seq）分析，并将其与 18 名成人（13 名患有 COVID-19）进行了比较。
儿童-成人整合的单细胞数据表明，患有该病的儿童在大多数主要免疫细胞类型中对 I 型干扰素表现出受抑制的反应，同时在单核细胞中抑制了干扰素调节因子和 Toll 样受体的表达，这通过干扰素刺激测定得到了证实。与成人患者不同，患有 COVID-19 的儿童表现出激活的促炎 CD14+单核细胞频率较低，这可能解释了他们中细胞因子风暴的罕见性。值得注意的是，儿科患者的自然杀伤（NK）细胞具有丰富的细胞毒性分子表达和上调的细胞毒性途径，表现出强大的细胞毒性，而细胞衰老以及 Notch 信号通路在 NK 细胞中显著下调，所有这些都表明 NK 细胞在儿童中的细胞毒性比成人患者更强，这通过 CD107a 脱颗粒测定得到了进一步证实。最后，与成人患者相比，儿童患者中幼稚 T 细胞较多，而激活和增殖的 T 细胞较少，幼稚 B 细胞较少，而激活的 B 细胞较多，这表明适应性免疫反应较弱。
总之，这项初步研究揭示了主要免疫细胞类型的细胞频率和激活状态的明显差异，特别是 PBMC 中更强大的 NK 细胞细胞毒性，这可能有助于保护儿童免受严重的 COVID-19 影响。
