Abstract / Summary
Abstract A key feature of immunosenescence is chronic low-grade inflammation, or inflammaging, which disrupts antigen-specific signaling and limits the magnitude, quality, and durability of vaccine-induced immunity. The study aimed to characterize the inflammatory response to viral infection through a comprehensive assessment of immune cells and cytokines in unvaccinated (NVP) and vaccinated patients (VP), and to investigate the impact of immunosenescence on vaccination effectiveness. The study included 79 patients aged 61.1 ± 16.7 years with newly diagnosed COVID-19 and 41 healthy, unvaccinated individuals aged 71.4 ± 4.5 years as healthy comparators (HC). Changes in neutrophil and lymphocyte counts resulted in the pan-immune-inflammation value (PIV) increase in infected patients (NVP 909 ± 1341, VP 1774 ± 2645) compared to HC (233 ± 204). Area under the curve (AUC) values derived from a multivariable logistic regression model for PIV and cytokines provided excellent discrimination between healthy individuals and infected patients: PIV + IL-1β (AUC = 0.909), PIV + IL-1Ra (AUC = 0.877), PIV + IL-6 (AUC = 0.898), and PIV + IL-8 (AUC = 1.000), PIV + IL-10 (AUC = 0.839) and PIV + TNFα (AUC = 0.998). Patients aged ≥65 years had significantly higher levels of IL-1β ( p = 0.036), IL-1Ra ( p = 0.025), IL-6 ( p = 0.026), IL-8 ( p = 0.014), IL-10 ( p = 0.005), TNFα ( p = 0.071) and INFγ ( p = 0.040) than those aged < 65, regardless of vaccination status. Overall, these findings reveal a complex interplay within the immune system in response to viral infection and vaccination. Age strongly shapes the immune response following vaccination by altering the numbers, distribution, and functional states of neutrophils, thereby complicating the course of COVID-19. The predictive value of neutrophil-related cytokines increased when PIV was included in inflammatory profiling.