Van de Garde Martijn D B, Miranda-Bedate Alberto, Nanlohy Nening M, Jacobi Ronald H J, Meijer Adam, Reukers Daphne F M, Van Beek Josine, Van Els Cecile A C M, Van Baarle Debbie, Rots Nynke Y, De Wit Jelle, Pinelli Elena
Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Front Immunol. 2024 Nov 18;15:1359993. doi: 10.3389/fimmu.2024.1359993. eCollection 2024.
To date, it is still not clear why during the COVID-19 pandemic children generally developed no or milder symptoms compared to adults. As innate immune responses are crucial in the early defense against pathogens, we aimed at profiling these responses from both adults and children with a primary SARS-CoV-2 infection.
In the first months of the pandemic, PBMCs and serum were collected from peripheral blood of adults and children at different time points after testing SARS-CoV-2 PCR positive (PCR+). The levels of SARS-CoV-2 Spike-specific IgG were measured in serum. The cells were cultured for 24 hours in medium only, with heat inactivated SARS-CoV-2 (iSARS-CoV-2) or toll-like receptor (TLR) ligands. The levels of secreted cytokines/chemokines as well as monocyte phenotype were determined.
Few days after testing PCR+, PBMCs from PCR+ children secreted higher levels of cytokines/chemokines compared to PCR+ adults, after these cells were incubated either in medium only or after stimulation with iSARS-CoV-2 or TLR ligands. Furthermore, PBMCs from children stimulated with iSARS-CoV-2 secreted significantly higher levels of IL-10 and GM-CSF compared to PBMCs from control children. In contrast, PBMCs from the PCR+ adults secreted lower levels of IL-8 compared to adult controls. Phenotypic analysis of monocytes indicates a smaller proportion non-classical monocytes for adults compared to children. The distinct cytokine profiles, symptom severity, and the proportion of non-classical monocytes correlated to each other. The levels of Spike-specific IgG overtime did not significantly differ between children and adults.
Within the first week after testing PCR+, children showed a stronger inflammatory innate immune profile and experienced less severe symptoms compared to adults. Our data implies correlations between the secretion of cytokines/chemokines, proportion of non-classical monocytes, and symptoms severity. These findings enhance our understanding of the distinct pediatric and adult innate immune profile after SARS-CoV-2 infection and contributes to the knowledge necessary to improve future prevention strategies.
迄今为止，仍不清楚为何在新冠疫情期间，儿童相较于成人通常症状不明显或症状较轻。由于先天免疫反应在早期抵御病原体方面至关重要，我们旨在对初次感染新冠病毒的成人和儿童的这些反应进行分析。
在疫情的最初几个月，在新冠病毒PCR检测呈阳性（PCR+）后的不同时间点，从成人和儿童的外周血中采集外周血单个核细胞（PBMC）和血清。检测血清中新冠病毒刺突蛋白特异性IgG的水平。将细胞仅在培养基中、用热灭活的新冠病毒（iSARS-CoV-2）或 Toll样受体（TLR）配体培养24小时。测定分泌的细胞因子/趋化因子水平以及单核细胞表型。
在PCR检测呈阳性几天后，与PCR+成人相比，PCR+儿童的PBMC在仅在培养基中培养或用iSARS-CoV-2或TLR配体刺激后，分泌的细胞因子/趋化因子水平更高。此外，与对照儿童的PBMC相比，用iSARS-CoV-2刺激的儿童PBMC分泌的IL-10和粒细胞-巨噬细胞集落刺激因子（GM-CSF）水平显著更高。相比之下，PCR+成人的PBMC与成人对照组相比，分泌的IL-8水平更低。单核细胞的表型分析表明，与儿童相比，成人中非经典单核细胞的比例更小。不同的细胞因子谱、症状严重程度和非经典单核细胞的比例相互关联。儿童和成人之间，刺突蛋白特异性IgG随时间的水平没有显著差异。
在PCR检测呈阳性后的第一周内，与成人相比，儿童表现出更强的炎症性先天免疫特征，且症状较轻。我们的数据表明细胞因子/趋化因子的分泌、非经典单核细胞的比例与症状严重程度之间存在相关性。这些发现增进了我们对新冠病毒感染后儿童和成人不同先天免疫特征的理解，并有助于积累改善未来预防策略所需的知识。
