Research questions
1. Do systemic cytokine and chemokine levels affect responses to infection and vaccination in older compared to younger adults? Is this mediated or confounded by frailty?
2. Does systemic cytokine and chemokine levels affect future frailty or sarcopenia?
3. Does medication affect response to infection and vaccination?
Objectives. (1) Quantify associations of cytokines/chemokines with incident infection following vaccination and associated adverse outcomes (1a) Test age differences and mediation/moderation by frailty. (2) Derive biomarker signatures predicting future frailty/sarcopenia (3) Evaluate medication effects on modulating the immune response to vaccination
Specifically, we would like to see this is the context of COVID-19, influenza, RSV (if available), and pneumococcal vaccination.
For outcomes, we are looking at:
1. Frailty/ sarcopenia measures: Edmonton, FRAIL, short physical performance battery, timed-up-and-go, handgrip strength, sit-to-stand, gait speed, ED5D, MoCA, composite measure of intrinsic capacity
2. Healthcare measures: GP or ED visits, hospitalisation for influenza, COVID-19 infections, pneumonia, cardiovascular disease; noninvasive positive pressure ventilation (NIPPV), invasive mechanical ventilation (IMV); ICU admissions; death due to cardiovascular disease, and all-cause mortality; antibiotic use, oral steroid use; WBC, CRP on admission
Scientific rationale: Inflammaging, a chronic low-grade inflammatory state of ageing, may attenuate vaccine responses, worsen infectious outcomes, and hasten functional decline. We have gathered preliminary evidence from our local cohort (NHG DSRB 2021/00049; 2023/01011) and am seeking validation in a larger cohort. UK Biobank’s proteomics, linked with functional and healthcare-utilisation records would enable us to conduct robust longitudinal analyses. Our findings will delineate high-risk profiles, and guide targeted vaccination and healthy-ageing strategies.