Increased serum catalytic iron may mediate tissue injury and death in patients with COVID-19

Abstract

The pathophysiology and the factors determining disease severity in COVID-19 are not yet clear, with current data indicating a possible role of altered iron metabolism. Previous studies of iron parameters in COVID-19 are cross-sectional and have not studied catalytic iron, the biologically most active form of iron. The study was done to determine the role of catalytic iron in the adverse outcomes in COVID-19. We enrolled adult patients hospitalized with a clinical diagnosis of COVID-19 and measured serum iron, transferrin saturation, ferritin, hepcidin and serum catalytic iron daily. Primary outcome was a composite of in-hospital mortality, need for mechanical ventilation, and kidney replacement therapy. Associations between longitudinal iron parameter measurements and time-to-event outcomes were examined using a joint model. We enrolled 120 patients (70 males) with median age 50 years. The primary composite outcome was observed in 25 (20.8%) patients-mechanical ventilation was needed in 21 (17.5%) patients and in-hospital mortality occurred in 21 (17.5%) patients. Baseline levels of ferritin and hepcidin were significantly associated with the primary composite outcome. The joint model analysis showed that ferritin levels were significantly associated with primary composite outcome [HR (95% CI) = 2.63 (1.62, 4.24) after adjusting for age and gender]. Both ferritin and serum catalytic iron levels were positively associated with in-hospital mortality [HR (95% CI) = 3.22 (2.05, 5.07) and 1.73 (1.21, 2.47), respectively], after adjusting for age and gender. The study shows an association of ferritin and catalytic iron with adverse outcomes in COVID-19. This suggests new pathophysiologic pathways in this disease, also raising the possibility of considering iron chelation therapy.

Figure 1

Shows the flow of the study.

Figure 2

Trajectories of iron parameters, by outcome status. (a) The two black curves present fitted trajectories of iron parameters—the solid black curve is for patients who had the event and the dashed black curve is for patients who recovered. (b) The blue triangles and lines present iron measurements and trajectories of individual patients who had the outcome. The pink dots and lines present iron measurements and trajectories of individual patients who did not have the outcome. (c) Notable is the finding that levels of ferritin and SCI continue to rise in patients who died while the survivors did not have the rise in levels. SCI–serum catalytic iron, SI–serum iron, TIBC- total iron binding capacity, TSAT–transferrin saturation.