Immunological Mechanisms Underlying Allergy Predisposition After SARS-CoV-2 Infection in Children

儿童感染SARS-CoV-2后过敏易感性的免疫机制

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Abstract

As the pediatric COVID-19 landscape evolves, it is essential to evaluate whether SARS-CoV-2 infection predisposes children to allergic disorders. This narrative review synthesizes current epidemiological and immunological evidence linking pediatric COVID-19 with new-onset atopy. Epidemiological data remain heterogeneous: large Korean and multinational cohorts report increased risks of asthma and allergic rhinitis following COVID-19, whereas U.S. cohorts show neutral or protective associations, highlighting geographic and methodological variability. Mechanistic insights provide biological plausibility: epithelial injury and the release of alarmin cytokines (IL-33, IL-25, TSLP) promote Th2 polarization and ILC2 expansion, while epigenetic "scars" (e.g., LMAN2 methylation changes) and hematopoietic stem cell reprogramming may sustain long-term Th2 bias. Cytokine memory involving IL-7 and IL-15 contributes to altered T- and B-cell homeostasis, whereas disrupted regulatory T-cell function may reduce tolerance thresholds. Paradoxical trade-offs exist, such as ACE2 downregulation in allergic airways, which may lower viral entry but simultaneously amplify type-2 inflammation. Together, these processes suggest that SARS-CoV-2 infection could foster a pro-allergic milieu in susceptible children. Although current evidence is inconclusive, integrating epidemiological surveillance with mechanistic studies is crucial for predicting and alleviating post-COVID allergic outcomes. Longitudinal pediatric cohorts and interventions targeting epithelial alarmins or microbiome restoration may hold promise for prevention.

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