Figure 1. Iron chelation therapy in SARS-CoV-2
infection.
The rapidity of the onset of inflammation in the acute phase of
SARS-CoV-2 infection provokes increased ferritin production to permit
adequate storage of iron and to deprive pathogen of iron. When the
binding capacity of transferrin in the blood is exceeded, iron is found
in the plasma as non-transferrin bound iron that changes to its redox
active form termed labile plasma iron (LPI). LPI correlates with
ferritin levels when in the cell contributes to the formation of
reactive oxygen species (ROS) that results in tissue damage and
subsequent fibrosis. Hyperinflammation with hyperferritinemia provokes
cytokine release with macrophage activation, with iron initially
accumulating in the reticuloendothelial macrophages and shedding of
CD163 as marker of macrophage activation. The massive interleukin
(IL)-1β release triggers a close autocrine loop leading to cytokine
storm with dramatic IL-6, IL-18 and ferritin production.
Iron chelation therapy can interrupt these steps. a) deferoxamine (DFO)
has a direct effect on ferritin since promotes ferritin degradation in
lysosomes by inducing autophagy. Both deferiprone and deferasirox are
likely to chelate cytosolic iron and iron which is extracted from
ferritin prior to ferritin degradation by proteasomes. b) DFO can induce
an up-regulation of IFN-γR2 expression on the cell surface on activated
T cells thus restoring T cell response to SARS-CoV-2 infection. c)
Deferasirox and DFO reduce fibrosis inhibiting the production of free
radicals, macrophage tissue infiltration and cause a remarkable decrease
of IL-6 levels.