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Review
. 2020 Aug:97:303-305.
doi: 10.1016/j.ijid.2020.05.110. Epub 2020 Jun 2.

Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?

Marvin Edeas  1 , Jumana Saleh  2 , Carole Peyssonnaux  3
Affiliations
Review

Iron: Innocent bystander or vicious culprit in COVID-19 pathogenesis?

Marvin Edeas et al. Int J Infect Dis. 2020 Aug.

Abstract

The coronavirus 2 (SARS-CoV-2) pandemic is viciously spreading through the continents with rapidly increasing mortality rates. Current management of COVID-19 is based on the premise that respiratory failure is the leading cause of mortality. However, mounting evidence links accelerated pathogenesis in gravely ill COVID-19 patients to a hyper-inflammatory state involving a cytokine storm. Several components of the heightened inflammatory state were addressed as therapeutic targets. Another key component of the heightened inflammatory state is hyper-ferritinemia which reportedly identifies patients with increased mortality risk. In spite of its strong association with mortality, it is not yet clear if hyper-ferritinemia in COVID-19 patients is merely a systemic marker of disease progression, or a key modulator in disease pathogenesis. Here we address implications of a possible role for hyper-ferritinemia, and altered iron homeostasis in COVID-19 pathogenesis, and potential therapeutic targets in this regard.

Keywords: Ferroptosis; Hyper-ferritinemia; Hypercoagulability; Iron homeostasis; Mitochondria; Oxidative stress.

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Figures

None
Graphical abstract
Figure 1
Figure 1
COVID-19 infection and Iron dysregulation. COVID-19 infection results in an inflammatory state involving a cytokine storm in COVID-19 patients. IL-6 stimulates ferritin and the synthesis of hepcidin. Hepcidin sequesters iron in the enterocytes and macrophages, leading to increased intracellular ferritin, and preventing iron efflux from enterocytes and macrophages. Excess intracellular iron interacts with molecular oxygen, generating reactive oxygen species (ROS) through Haber-Weiss and Fenton reactions and reactive nitrogen species (RNS) and reactive sulfur species (RSS). The intracellular iron excess leads to ferroptosis, a process of programmed cell death. Iron overload may also affect extra and intracellular mitochondria function and microbiota diversity (lungs and gut) and blood coagulation.
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