Extreme imbalance in iron metabolism amongst SARS-CoV-2 contaminated sufferers is distinguished in each symptomatic (gentle, average to extreme) scientific part of COVID-19. Part-I – Hypoxia correlates with decreased O2 transport by erythrocytes, overexpression of HIF-1α, altered mitochondrial bioenergetics with host metabolic reprogramming (HMR). Part-II – Hyperferritinemia outcomes from an elevated iron overload, which triggers a fulminant proinflammatory response – the acute cytokine launch syndrome (CRS). Elevated cytokine ranges (i.e. IL6, TNFα and CRP) strongly correlates with altered ferritin/TF ratios in COVID-19 sufferers. Part-III – Thromboembolism is consequential to erythrocyte dysfunction with heme launch, elevated prothrombin time and elevated D-dimers, cumulatively linked to extreme coagulopathies with life-threatening outcomes corresponding to ARDS, and multi-organ failure. Taken collectively, Fe-R-H dysregulation is implicated in each symptomatic part of COVID-19. Fe-R-H regulators corresponding to lactoferrin (LF), hemoxygenase-1 (HO-1), erythropoietin (EPO) and hepcidin modulators are innate bio-replenishments that sequester iron, neutralize iron-mediated free radicals, cut back oxidative stress, and enhance host protection by optimizing iron metabolism. On account of its pivotal position in ‘cytokine storm’, ferroptosis is a possible intervention goal. Ferroptosis inhibitors corresponding to ferrostatin-1, liproxstatin-1, quercetin, and melatonin may forestall mitochondrial lipid peroxidation, up-regulate antioxidant/GSH ranges and abrogate iron overload-induced apoptosis by means of activation of Nrf2 and HO-1 signaling pathways. Iron chelators corresponding to heparin, deferoxamine, caffeic acid, curcumin, α-lipoic acid, and phytic acid may defend in opposition to ferroptosis and restore mitochondrial perform, iron-redox potential, and rebalance Fe-R-H standing. Due to this fact, Fe-R-H restoration is a number biomarker-driven potential fight technique for an efficient scientific and post-recovery administration of COVID-19.