Rewired type I IFN signaling is linked to age-dependent differences in COVID-19.

ABSTRACT: Advanced age is the most important risk factor for severe disease or death from COVID-19, but a thorough mechanistic understanding of the molecular and cellular underpinnings is lacking. Multi-omics analysis of 164 samples from SARS-CoV-2-infected persons aged 1 to 84 years reveals a rewiring of type I interferon (IFN) signaling with a gradual shift from signal transducer and activator of transcription 1 (STAT1) to STAT3 activation in monocytes, CD4⁺ T cells, and B cells with increasing age. Diversion of IFN signaling is associated with increased expression of inflammatory markers, enhanced release of inflammatory cytokines, and delayed contraction of infection-induced CD4⁺ T cells. A shift from IFN-responsive germinal center B (GCB) cells toward CD69^high G

SUBMITTER: Petrov L 

PROVIDER: S-EPMC12432374 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature