From cells to antibodies: age-specific immune shifts in children during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic and associated containment measures could have influenced children's immune system development through reduced microbial exposure and lifestyle changes. Hematological parameters and immunoglobulin E (IgE) are key indicators for immune status, but large-scale, age-stratified studies are lacking. METHODS: Children under 18 years were enrolled during the first two weeks of December each year from 2017 to 2024 at Tianjin Children's hospital. Data from 2019 and 2022 were excluded to minimize COVID-19 pandemic effects. Cases with missing age/sex or IgE values outside the linear range were removed. Complete blood count (CBC) data were obtained from emergency department patients (n=126, 617), and IgE levels from inpatient admissions patients (n=6, 055). General linear models (GLM) adjusted for sex and age were used to compare pre-pandemic (2017 and 2018) and post-pandemic groups (2023 and 2024). Effect sizes (η²) were calculated. Age-stratified analyses were performed in five subgroups: ≤1 year, 2-3 years, 4-6 years, 7-12 years, and 13-18 years. Baseline characteristics were compared between cohorts using chi-square test for sex and Mann-Whitney U test for age. RESULTS: Baseline comparison showed no significant sex difference between the CBC and IgE cohorts (χ² = 3.111, p = 0.078; Fisher's exact test p = 0.079), but age differed significantly (Mann-Whitney U = 3, 535, 702.5, Z = -130.805, p < 0.001). In the whole-age model, only basophils showed a significant difference (η²=0.038, p < 0.001); other CBC parameters had η²≤0.001. Age-stratified analysis revealed an inverted U-shaped trend for basophils, with the largest effect in children aged 4-6 years (η² = 0.051). For IgE, the whole-age model showed a small increase post-pandemic (η² = 0.013, p < 0.001). Age-stratified analysis demonstrated that the difference was confined to children aged 7-18 years (η² = 0.017-0.018, p < 0.01), with no significant changes in younger age groups. CONCLUSIONS: The COVID-19 pandemic was associated with modest increases in basophils and IgE in children, with distinct age-dependent patterns: basophils peaked in preschool children (4-6 years), while IgE increased only in adolescents (7-18 years). These findings support the hygiene hypothesis and suggest the age stratified pattern of Th2-skewed immune shifts across childhood. However, all effect sizes were small, indicating that routine CBC and IgE are not sensitive markers for individual monitoring.