Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection

Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection

Abstract 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 in...

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Main Authors: Jillian H. Hurst, Aditya A. Mohan, Trisha Dalapati, Ian A. George, Jhoanna N. Aquino, Debra J. Lugo, Trevor S. Pfeiffer, Javier Rodriguez, Alexandre T. Rotta, Nicholas A. Turner, Thomas W. Burke, Micah T. McClain, Ricardo Henao, C. Todd DeMarco, Raul Louzao, Thomas N. Denny, Kyle M. Walsh, Zhaohui Xu, Asuncion Mejias, Octavio Ramilo, Christopher W. Woods, Matthew S. Kelly
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57655-3
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Summary:Abstract 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.
ISSN:2041-1723

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