The Association Between Peak IL-6 Levels, In-Hospital Mortality, and Selected Risk Factors in Patients Hospitalized...

Introduction: Interleukin-6 is one of the key mediators of the inflammatory response and has repeatedly been associated with severe COVID-19 and an increased risk of death. However, its clinical significance depends on the timing of measurement, the characteristics of the study population, and the organizational context of care. Data on the significance of IL-6 in temporary hospital settings remain limited. Objective: The objective of this study was to assess the association between the highest available interleukin-6 (IL-6) concentration recorded during hospitalization and in-hospital mortality among patients hospitalized for COVID-19 at the Temporary Hospital in Gdansk. Additional objectives were to assess the ability of IL-6 to discriminate in-hospital mortality, determine an exploratory cutoff point for the study cohort, and assess selected clinical factors associated with elevated IL-6 concentrations. Materials and Methods: A retrospective, single-center cohort study was conducted involving 1214 patients hospitalized for COVID-19 during two periods of operation of the Temporary Hospital in Gdansk. IL-6 measurements were performed selectively, at the discretion of the attending physician; therefore, IL-6 analyses were conducted in a subcohort of 171 patients with an available result. The highest available IL-6 concentration recorded during each patient's hospitalization was used in the analysis. Patients with and without an IL-6 measurement were compared. The association between IL-6 and in-hospital mortality was assessed using ROC analysis and a multivariable logistic regression model in which IL-6 was analyzed as a continuous variable after log₂ transformation. Results: A total of 230 in-hospital deaths were recorded in the entire cohort. IL-6 was measured in 171 patients. Patients with an IL-6 measurement differed from the remaining hospitalized patients in terms of age, sex, year of hospitalization, mortality, length of hospital stay, and the prevalence of respiratory disease, indicating the clinically selective nature of this subcohort. ROC analysis for IL-6 levels yielded an AUC of 0.73, and the cutoff point determined using the Youden method was 94.3 pg/mL. In the multivariable logistic regression model, log₂-transformed IL-6 remained associated with in-hospital mortality after adjustment for age, year of hospitalization, and respiratory disease. A two-fold increase in IL-6 concentration was associated with an approximately 27.5% increase in the odds of death. Conclusions: The highest available IL-6 concentration recorded during hospitalization was associated with in-hospital mortality in the analyzed subcohort of patients hospitalized for COVID-19. The findings support the relevance of IL-6 as a marker of an intensified inflammatory response during hospitalization, but should not be interpreted as validation of IL-6 as a standalone prognostic tool measured at hospital admission.