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

tetano

Editor, Senior Moderator
Nat Commun


. 2025 Mar 10;16(1):2383.
doi: 10.1038/s41467-025-57655-3. Age-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection

Jillian H Hurst[SUP] #[/SUP][SUP] 1 2 [/SUP], Aditya A Mohan[SUP] #[/SUP][SUP] 3 [/SUP], Trisha Dalapati[SUP] 4 [/SUP], Ian A George[SUP] 5 [/SUP], Jhoanna N Aquino[SUP] 1 [/SUP], Debra J Lugo[SUP] 1 [/SUP], Trevor S Pfeiffer[SUP] 1 [/SUP], Javier Rodriguez[SUP] 6 [/SUP], Alexandre T Rotta[SUP] 7 [/SUP], Nicholas A Turner[SUP] 8 [/SUP], Thomas W Burke[SUP] 8 9 [/SUP], Micah T McClain[SUP] 8 9 10 [/SUP], Ricardo Henao[SUP] 11 12 [/SUP], C Todd DeMarco[SUP] 13 [/SUP], Raul Louzao[SUP] 13 [/SUP], Thomas N Denny[SUP] 13 [/SUP], Kyle M Walsh[SUP] 2 14 [/SUP], Zhaohui Xu[SUP] 15 [/SUP], Asuncion Mejias[SUP] 15 [/SUP], Octavio Ramilo[SUP] 15 [/SUP], Christopher W Woods[SUP] 8 9 10 13 [/SUP], Matthew S Kelly[SUP] 16 [/SUP]



Affiliations
Free PMC article 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.


 
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