Covid-19:And hypoxiahemoglobin,beyond inflammation.iron, a narrative review

Abstract

Coronavirus disease-19 (COVID-19) has been regarded as an infective-inflam-matory disease, which affects mainly lungs. More recently, a multi-organ involvement has been highlighted, with different pathways of injury. A hemoglobinopathy, hypoxia and cell iron overload might have a possible additional role. Scientific literature has pointed out two potential pathophysio-logical mechanisms: i) severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) interaction with hemoglobin molecule, through CD147, CD26 and other receptors located on erythrocyte and/or blood cell precursors; ii) hepcidin-mimetic action of a viral spike protein, inducing ferroportin blockage. In this translational medicine-based narrative review, the following patho-logic metabolic pathways, deriving from hemoglobin denaturation and iron metabolism dysregulation, are highlighted: i) decrease of functioning hemoglobin quote; ii) iron overload in cell/tissue (hyper-ferritinemia); iii) release of free toxic circu-lating heme; iv) hypoxemia and systemichypoxia; v) reduction of nitric oxide; vi) coagulation activation; vii) ferroptosis with oxidative stress and lipoperoxidation; viii) mitochondrial degeneration and apoptosis. A few clinical syndromes may follow, such as pulmonary edema based on arterial vaso-constriction and altered alveolo-capillary barrier, sideroblastic-like anemia, endothe-liitis, vasospastic acrosyndrome, and arte-rio-venous thromboembolism. We speculat-ed that in COVID-19, beyond the classical pulmonary immune-inflammation view, the occurrence of an oxygen-deprived blood disease, with iron metabolism dysregula-tion, should be taken in consideration. A more comprehensive diagnostic/therapeutic approach to COVID-19 is proposed, includ-ing potential adjuvant interventions aimed at improving hemoglobin dysfunction, iron over-deposit and generalized hypoxic state.