Hurst, Jillian HMohan, Aditya ADalapati, TrishaGeorge, Ian AAquino, Jhoanna NLugo, Debra JPfeiffer, Trevor SRodriguez, JavierRotta, Alexandre TTurner, Nicholas ABurke, Thomas WMcClain, Micah THenao, RicardoDeMarco, C ToddLouzao, RaulDenny, Thomas NWalsh, Kyle MXu, ZhaohuiMejias, AsuncionRamilo, OctavioWoods, Christopher WKelly, Matthew S2025-04-012025-04-012025-032041-17232041-1723https://hdl.handle.net/10161/32158Age 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.https://creativecommons.org/licenses/by-nc/4.0HumansAge FactorsAdolescentAdultAgedAged, 80 and overMiddle AgedChildChild, PreschoolInfantInfant, NewbornFemaleMaleImmunity, InnateYoung AdultAdaptive ImmunityTranscriptomeCOVID-19SARS-CoV-2Journal article