COVID-19 patients develop acute renal failure, severe hypoxia with relatively preserved lung compliance despite ARDS, and in some cases significant cardiac arrhythmias. Deferoxamine (DFX) may represent one treatment option. The functional receptor for coronavirus invasion is the angiotensin-converting enzyme 2 (ACE2). Patients with underlying cardiovascular disease suffer more severe COVID-19 symptoms, associated with increased expression of ACE2. The virus causes damage through widespread pro-inflammatory cytokine responses and the induction of procoagulant factors. Iron (Fe++) may contribute to this. Fe++ is required for both host and pathogen and iron deficiency can impair host immunity, while iron overload can cause oxidative stress to propagate harmful viral mutations. The effect of the virus on the hemoglobin (Hb) molecule has been recently described. A study using conserved domain analysis homology modeling, and molecular docking compared the biological roles of certain proteins of the SARS-CoV-2 virus and its interaction with Hb. Orf1 ab, ORF10, and ORF3a viral proteins attack the heme on the 1-beta chain of Hb to dissociate the Fe++ to form porphyrin.5 This reduces oxygen-carrying capacity, but importantly, the liberated Fe++ molecule is highly toxic when not bound to a protein or adsorbed and transported by ferritin.6 The high ferritin levels in the COVID-19 population, though attributed to acute phase reactants,7 may play a role in the binding of this free Fe++ molecule in an attempt to obviate its toxic effects. The free radicals produced by the liberated Fe++ promulgate a cascade of inflammatory reactions and microvascular thrombosis. A high level of Fe++ may be less apparent systemically but a high relative concentration in the microcirculation leads to the deleterious effects of free radical generation. This contributes to microvascular thrombosis and end-organ damage. This process raises the potential of a role for (DFX) as a therapeutic option.
