tetano
Editor, Senior Moderator
Cell Rep Med
. 2025 Aug 19;6(8):102285.
doi: 10.1016/j.xcrm.2025.102285. Rewired type I IFN signaling is linked to age-dependent differences in COVID-19
Lev Petrov[SUP] 1 [/SUP], Sophia Brumhard[SUP] 1 [/SUP], Sebastian Wisniewski[SUP] 2 [/SUP], Philipp Georg[SUP] 1 [/SUP], David Hillus[SUP] 3 [/SUP], Anna Hiller[SUP] 1 [/SUP], Rosario Astaburuaga-García[SUP] 4 [/SUP], Nils Blüthgen[SUP] 4 [/SUP], Emanuel Wyler[SUP] 5 [/SUP], Katrin Vogt[SUP] 1 [/SUP], Hannah-Philine Dey[SUP] 1 [/SUP], Saskia von Stillfried[SUP] 6 [/SUP], Christina Iwert[SUP] 1 [/SUP], Roman D Bülow[SUP] 6 [/SUP], Bruno Märkl[SUP] 7 [/SUP], Lukas Maas[SUP] 1 [/SUP], Christine Langner[SUP] 8 [/SUP], Tim Meyer[SUP] 9 [/SUP], Jennifer Loske[SUP] 10 [/SUP], Roland Eils[SUP] 11 [/SUP], Irina Lehmann[SUP] 11 [/SUP], Benjamin Ondruschka[SUP] 12 [/SUP], Markus Ralser[SUP] 13 [/SUP], Jakob Trimpert[SUP] 8 [/SUP], Peter Boor[SUP] 14 [/SUP], Sammy Bedoui[SUP] 15 [/SUP], Christian Meisel[SUP] 9 [/SUP], Marcus A Mall[SUP] 16 [/SUP], Victor M Corman[SUP] 17 [/SUP], Leif Erik Sander[SUP] 1 [/SUP], Jobst Röhmel[SUP] 18 [/SUP], Birgit Sawitzki[SUP] 19 [/SUP]
Affiliations
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[SUP]+[/SUP] 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[SUP]+[/SUP] T cells. A shift from IFN-responsive germinal center B (GCB) cells toward CD69[SUP]high[/SUP] GCB and atypical B cells during aging correlates with immunoglobulin (Ig)A production in children, whereas complement-fixing IgG predominates in adults. Our data provide a mechanistic basis for inflammation-prone responses to infections and associated pathology during aging.
Keywords: B cells; COVID-19; SARS-CoV-2; STAT1; STAT3; T cells; age; antibodies; children; immune response; monocytes; signaling; type I IFN.
. 2025 Aug 19;6(8):102285.
doi: 10.1016/j.xcrm.2025.102285. Rewired type I IFN signaling is linked to age-dependent differences in COVID-19
Lev Petrov[SUP] 1 [/SUP], Sophia Brumhard[SUP] 1 [/SUP], Sebastian Wisniewski[SUP] 2 [/SUP], Philipp Georg[SUP] 1 [/SUP], David Hillus[SUP] 3 [/SUP], Anna Hiller[SUP] 1 [/SUP], Rosario Astaburuaga-García[SUP] 4 [/SUP], Nils Blüthgen[SUP] 4 [/SUP], Emanuel Wyler[SUP] 5 [/SUP], Katrin Vogt[SUP] 1 [/SUP], Hannah-Philine Dey[SUP] 1 [/SUP], Saskia von Stillfried[SUP] 6 [/SUP], Christina Iwert[SUP] 1 [/SUP], Roman D Bülow[SUP] 6 [/SUP], Bruno Märkl[SUP] 7 [/SUP], Lukas Maas[SUP] 1 [/SUP], Christine Langner[SUP] 8 [/SUP], Tim Meyer[SUP] 9 [/SUP], Jennifer Loske[SUP] 10 [/SUP], Roland Eils[SUP] 11 [/SUP], Irina Lehmann[SUP] 11 [/SUP], Benjamin Ondruschka[SUP] 12 [/SUP], Markus Ralser[SUP] 13 [/SUP], Jakob Trimpert[SUP] 8 [/SUP], Peter Boor[SUP] 14 [/SUP], Sammy Bedoui[SUP] 15 [/SUP], Christian Meisel[SUP] 9 [/SUP], Marcus A Mall[SUP] 16 [/SUP], Victor M Corman[SUP] 17 [/SUP], Leif Erik Sander[SUP] 1 [/SUP], Jobst Röhmel[SUP] 18 [/SUP], Birgit Sawitzki[SUP] 19 [/SUP]
Affiliations
- PMID: 40834853
- DOI: 10.1016/j.xcrm.2025.102285
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[SUP]+[/SUP] 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[SUP]+[/SUP] T cells. A shift from IFN-responsive germinal center B (GCB) cells toward CD69[SUP]high[/SUP] GCB and atypical B cells during aging correlates with immunoglobulin (Ig)A production in children, whereas complement-fixing IgG predominates in adults. Our data provide a mechanistic basis for inflammation-prone responses to infections and associated pathology during aging.
Keywords: B cells; COVID-19; SARS-CoV-2; STAT1; STAT3; T cells; age; antibodies; children; immune response; monocytes; signaling; type I IFN.