Predicting critical care outcomes in acute respiratory infections: The interplay between host comorbidities and immune status

Abstract

Acute respiratory infections (ARIs) are a major cause of global critical illness and remain a leading reason for intensive care unit (ICU) admission and mortality. While pathogen-related factors and treatment timing have long dominated prognostic research, recent evidence highlights the decisive influence of host characteristics, particularly comorbidities and immune competence, on clinical outcomes. Chronic diseases such as diabetes, cardiovascular disorders, chronic kidney or liver disease, and chronic obstructive pulmonary disease substantially modify the course of ARIs by amplifying systemic inflammation, altering immune regulation, and impairing pulmonary and multi-organ recovery. Similarly, primary and secondary immunosuppression arising from malignancy, transplantation, or therapeutic interventions further increase the risk of severe infection, ventilator dependency, and mortality. Despite these associations, current prognostic models in respiratory critical care largely depend on physiologic or pathogen-specific variables, overlooking the complex host interplay that determines disease severity and treatment response. This narrative review synthesizes contemporary evidence on how comorbidities and immune alterations shape outcomes in critically ill patients with ARIs, with a focus on mortality, duration of mechanical ventilation, and ICU length of stay. It addresses key research questions regarding the relative contribution of host versus pathogen factors, the prognostic value of immune-inflammatory biomarkers, and the potential integration of host data into predictive models. Understanding this interplay is essential for advancing precision critical care, guiding individualized management, and informing the development of ethical, host-inclusive frameworks for ICU triage and resource allocation in increasingly multimorbid populations.