5 questions forInterview
New insights provide the basis for the development of age-dependent and individually tailored therapies adapted to the immune system
Age is a critical factor for the severity and progression of COVID-19. However, the precise molecular and cellular mechanisms remain largely unclear to this day. Scientists at the Berlin Institute of Health in the Charité (BIH) and Charité – Universitätsmedizin Berlin have conducted a comprehensive study illuminating the immunological processes during SARS-CoV-2 infections across all age groups. In an interview, Prof. Dr. Birgit Sawitzki, head of the study, talks about her research results.
What question did you want to answer, what were you particularly interested in?
We wanted to understand why children are significantly more resilient to severe COVID-19 progression compared to adults. We were particularly interested in whether age-dependent differences in immune cell activation and signaling pathways could explain this resilience. The aim was to identify immunological clues to this protective mechanism and support them with mechanistic investigations.
What specific challenges did you face when developing your approach?
A key challenge was the integration of different single-cell analyses – particularly single-cell transcriptomic and proteomic analyses-across a diverse age cohort ranging from 1 to 84 years. With children, in particular, we had to work with very limited blood volumes, which required highly sensitive and reproducible methods. Collecting and analyzing age-spanning data was methodologically complex but enabled, for the first time, a systematic characterization of age-dependent immune responses.
What surprised you and why? What was new?
Surprisingly, immune cells respond differently to certain soluble messengers (type I interferons) with increasing age: they progressively activate an alternative signaling pathway that switches on a different transcription factor (STAT3 instead of STAT1). This shift affects how genes are regulated within the immune cells. This previously unknown mechanism was associated with a more prolonged and inflammatory immune response. Remarkably, this shift began as early as around 12 years of age—the same age when the first symptoms of post-acute infection syndrome (PAIS) tend to appear.
What significance could this success have for future patients?
Our findings provide a basis for better understanding age-dependent immune responses. This could help identify patient groups at higher risk of excessive or dysregulated immune reactions at an earlier stage and allow for more targeted treatment—such as through immunomodulatory therapies or individualized monitoring.
Where do you see the translational bridge between research and application?
Our insights lay an important foundation for the development of age-specific immunomodulatory therapies and tailored vaccination strategies. By precisely characterizing immune cell states and signaling networks, new markers for diagnostics and therapy can be identified and purposefully translated into clinical applications.