biostudies-literatureHurst JHNIAID NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)2383https://www.ebi.ac.uk/biostudies/studies/S-EPMC11894178biostudies-literatureUnknown16(1)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 inNature communicationsAge-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection.PMC11894178R01-AI161008, K23-AI135090, K23-AI135090K01 AI173398Mohan AAHenao RKelly MSHurst JHRodriguez JLugo DJRamilo OBurke TWMejias ADeMarco CTLouzao RAquino JNTurner NAWoods CWWalsh KMRotta ATDalapati TPfeiffer TSMcClain MTDenny TNGeorge IAXu ZfalseAge-associated differences in mucosal and systemic host responses to SARS-CoV-2 infection.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 in2025-01-01T00:00:00Z2025 Mar2025-04-26T02:47:29.917Z2025-04-06T10:34:22.365ZS-EPMC118941784006487010.1038/s41467-025-57655-3