Immune response dynamics in severe infection

This thesis investigates the dynamics of the immune response in severe infections, focusing on the longitudinal host response and the impact of immunomodulatory therapies. Despite recent advances, particularly in the application of immunotherapy for sepsis, identifying the appropriate patient population for these therapies remains a significant challenge. This difficulty arises from the substantial heterogeneity – both clinically and biologically – among those affected.
This research examines the longitudinal host immune response in various clinical cohorts, including hospitalized patients with infections like sepsis, pneumonia, and COVID-19. We analyzed plasma protein biomarkers and gene expression profiles over time to study two key areas: the influence of immunomodulatory treatments on the longitudinal host response and the characterization of immune dysregulation in patients with nosocomial infections, such as ICU-acquired pneumonia or cytomegalovirus reactivation. Our findings advance our understanding of immune regulation in severe infections, emphasizing the importance of tailoring therapies to patient-specific immune profiles. Additionally, this work provides a practical framework for incorporating biological data into clinical trials, potentially leading to the development of novel therapeutic targets and enhancing personalized medicine strategies.