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.

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

“…A consequence of cell death, such as occurs in endotheliopathy, is the release in COVID patients of the normally intracellular iron storage protein ferritin [237,238], which can then release free iron [239]. Iron dysregulation is an accompaniment to a huge number of chronic, inflammatory diseases [200,240,241], and iron dysregulation is a significant accompaniment in COVID [238,[242][243][244][245]. Indeed, there is evidence that SARS-CoV-2 can release iron from haemoglobin directly [246].…”

Inhibiting ACSL1-Related Ferroptosis Restrains Murine Coronavirus Infection

“…Because COVID-19 patients suffered from systemic hyper-inflammation, characterized by ROS elevation and cytokine storm, SARS-CoV-2 infection was predicted to involve ferroptosis [34][35][36]. The prediction was also evidenced by the elevated serum iron load in COVID-19 patients, and the decreased GPX4 expression in SARS-CoV-2 infected cells [37][38][39]. Here, we checked whether and how ferroptosis was involved in MHV-A59 infection.…”

Deciphering the immunoboosting potential of macro and micronutrients in COVID support therapy

“…It is proposed that SARS-CoV-2 may need iron for replication and other roles, offering a prospective mechanism for greater pathogenicity in the existence of high SCI. Chakurkar et al 2021 reported the role of ferrotoxicity in COVID-19 and the concept that SCI is a sign of poor results in COVID-19. Tissue injury either from a direct cytopathic effect can result in rise in their level or inflammation or ischemia leads to a burst release of intracellular iron stores (Chakurkar et al 2021 ).…”

“…Chakurkar et al 2021 reported the role of ferrotoxicity in COVID-19 and the concept that SCI is a sign of poor results in COVID-19. Tissue injury either from a direct cytopathic effect can result in rise in their level or inflammation or ischemia leads to a burst release of intracellular iron stores (Chakurkar et al 2021 ).…”