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Increased serum catalytic iron may mediate tissue injury and death in patients with COVID-19
Vipul Chakurkar1, Mohan Rajapurkar2, Suhas Lele2
1Renal Unit, Department of Medicine, KEM Hospital, Sardar Moodliar Road, Rasta Peth, Pune, Maharashtra, 411011, India. chakurkarvipul@gmail.com.
Insights
Altered iron metabolism, specifically elevated ferritin and catalytic iron, is linked to severe COVID-19 outcomes. This finding suggests new disease pathways and potential iron chelation therapies for critical illness.
Area of Science:
- Biochemistry
- Infectious Diseases
- Critical Care Medicine
Background:
- The precise factors influencing COVID-19 severity remain unclear, with emerging evidence pointing to dysregulated iron metabolism.
- Previous research on iron parameters in COVID-19 has been limited by cross-sectional designs and has not assessed biologically active catalytic iron.
- Understanding the role of specific iron forms is crucial for elucidating COVID-19 pathophysiology.
Purpose of the Study:
- To investigate the association between catalytic iron and adverse outcomes in hospitalized COVID-19 patients.
- To examine the relationship between longitudinal measurements of various iron parameters and clinical outcomes.
- To identify potential therapeutic targets related to iron metabolism in severe COVID-19.
Main Methods:
- Adult patients hospitalized with COVID-19 were enrolled.
- Daily measurements of serum iron, transferrin saturation, ferritin, hepcidin, and serum catalytic iron were conducted.
- A joint model was employed to analyze the association between longitudinal iron parameter data and time-to-event outcomes, including a composite of mortality, mechanical ventilation, and kidney replacement therapy.
Main Results:
- A total of 120 patients were included; 20.8% experienced the primary composite outcome.
- Elevated baseline ferritin and hepcidin levels were significantly associated with the primary composite outcome.
- Longitudinal analysis revealed that higher ferritin levels (HR=2.63) and catalytic iron levels (HR=1.73) were independently associated with increased risk of adverse outcomes, including in-hospital mortality.
Conclusions:
- This study demonstrates a significant association between ferritin and catalytic iron levels and adverse outcomes in COVID-19 patients.
- These findings suggest novel pathophysiological mechanisms involving iron dysregulation in severe COVID-19.
- The results highlight the potential of iron chelation therapy as a therapeutic strategy for managing critical COVID-19 illness.
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.
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