Iron Dysregulation During Severe COVID-19: Longitudinal Evidence from Hospitalized Patients

Background/Objectives: The COVID-19 pandemic underlined the critical role of iron homeostasis in infections, particularly in those cases where hyperinflammation, fueled by massive elevation in cytokines such as IL-6, TNF-α, and IL-8, triggered acute respiratory distress syndrome (ARDS), progressive multiorgan failure and heightened mortality. This extreme immune response aggravates systemic iron imbalance and eventually triggers a vicious cycle in which the inflammatory state fuels the impaired iron metabolism, thereby contributing to disease severity. The main goal of this work was to disentangle the relationships between inflammation and iron metabolism in a cohort of well-characterized patients hospitalized for severe COVID-19. Methods: This study evaluated 389 patients hospitalized with COVID-19 pneumonia in a medical ward at Verona University Hospital. Complete clinical parameters, inflammatory, and iron-related markers’ trends were analyzed over time during hospitalization (admission (T0), 1 week (T1), and 2 weeks after (T2)). Subjects were grouped by disease severity during hospitalization. Results: High-severity cases showed significantly higher concentrations of IL-8, IL-6, IL-10, hepcidin, and ferritin at baseline. Hepcidin correlated strongly with inflammatory markers and was a predictor of COVID-19 severity (p = 0.014). Despite a gradual decrease, hepcidin levels remained significantly higher in patients with a more serious form of the disease across time points. Conclusions: Our findings underscore the clinical utility of iron-related markers in COVID-19 management and the relevance of their assessment in clinical settings for better patient stratification.