Objective: To evaluate the association between iron metabolism indicators and disease severity in hospitalized patients with coronavirus disease 2019 (COVID-19). Design: Two-center observational study Setting: A university hospital and a core hospital in Yokohama, Japan Patients: Adults with COVID-19 whose serum iron levels were measured within the first 5 days of hospitalization were included. Patients who refused mechanical ventilation were excluded from the study. Measurements and Main Results: One hundred thirty-six patients were included in this study. We analyzed the association between COVID-19 severity and serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT) levels. Disease severity was defined as the worst respiratory status during hospitalization. Serum iron levels were significantly lower in patients with mild respiratory failure (RF) (n=55, median serum iron level: 24 [interquartile range: 19-42] mg/dL) than in the non-RF group (n=44, 40 [24-80] mg/dL) and the severe RF group (n=37, 60 [23.5-87] mg/dL); however, there were no significant differences in iron levels between the non-RF and severe RF groups (non-RF vs. mild RF: p=0.019, non-RF vs. severe RF: p>0.999, and mild RF vs. severe RF: p=0.009). That is, there was a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron or TSAT levels were independently associated with development of severe RF. Conclusions: A U-shaped association between serum iron level and RF severity in hospitalized COVID-19 patients was observed. Higher serum iron levels in COVID-19 patients with RF are associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.
The U-shaped association of serum iron level with COVID-19 severity: Is iron a potential therapeutic target?