Hurst Jillian H, Mohan Aditya A, Dalapati Trisha, George Ian A, Aquino Jhoanna N, Lugo Debra J, Pfeiffer Trevor S, Rodriguez Javier, Rotta Alexandre T, Turner Nicholas A, Burke Thomas W, McClain Micah T, Henao Ricardo, DeMarco C Todd, Louzao Raul, Denny Thomas N, Walsh Kyle M, Xu Zhaohui, Mejias Asuncion, Ramilo Octavio, Woods Christopher W, Kelly Matthew S
Department of Pediatrics, Division of Infectious Diseases, Duke University School of Medicine, Durham, NC, USA.
Children's Health and Discovery Institute, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Nat Commun. 2025 Mar 10;16(1):2383. doi: 10.1038/s41467-025-57655-3.
Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. Here we describe upper respiratory tract (URT) and peripheral blood transcriptomes of 202 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 65 healthy individuals. Among healthy children and adolescents, younger age is associated with higher URT expression of innate and adaptive immune pathways. SARS-CoV-2 infection induces broad upregulation of URT innate and adaptive immune responses among children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents are dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways is observed only in adults. Among SARS-CoV-2-infected individuals, fever is associated with blunted URT immune responses and more pronounced systemic immune activation. These findings demonstrate that immune responses to SARS-CoV-2 differ across the lifespan, from distinct signatures in childhood and adolescence to age-associated alterations in adults.
年龄是新冠病毒感染导致严重后果的最强风险因素之一。在此，我们描述了202名参与者（年龄范围为1周龄至83岁）的上呼吸道（URT）和外周血转录组，其中包括137名轻度新冠病毒感染的非住院个体和65名健康个体。在健康儿童和青少年中，年龄越小，上呼吸道先天免疫和适应性免疫途径的表达越高。新冠病毒感染在儿童和青少年中诱导上呼吸道先天免疫和适应性免疫反应广泛上调。新冠病毒感染儿童和青少年的外周血反应以干扰素途径为主，而髓系激活、炎症和凝血途径的上调仅在成人中观察到。在新冠病毒感染个体中，发热与上呼吸道免疫反应减弱和更明显的全身免疫激活有关。这些发现表明，对新冠病毒的免疫反应在整个生命周期中有所不同，从儿童期和青少年期的独特特征到成人期与年龄相关的变化。
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