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Brief Report

COVID-19: Hemoglobin, Iron, and Hypoxia beyond Inflammation. A Narrative Review

Eurocenter Venalinfa, San Benedetto del Tronto (AP), Italy
Primary Care and Territorial Health Unit, Social Security Institute, Cailungo, San Marino
ARNAS Civico Di Cristina Benfratelli Hospital Trust, Palermo; PROMISE Department, University of Palermo School of Medicine, Palermo, Italy
Author to whom correspondence should be addressed.
Clin. Pract. 2020, 10(2), 1271;
Received: 26 May 2020 / Revised: 26 May 2020 / Accepted: 28 May 2020 / Published: 28 May 2020


Coronavirus disease-19 (COVID-19) has been regarded as an infective-inflammatory 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 pathophysiological 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 pathologic metabolic pathways, deriving from hemoglobin denaturation and iron metabolism dysregulation, are highlighted: i) decrease of functioning hemoglobin quote; ii) iron overload in cell/tissue (hyperferritinemia); iii) release of free toxic circulating heme; iv) hypoxemia and systemic hypoxia; 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 vasoconstriction and altered alveolo-capillary barrier, sideroblastic-like anemia, endotheliitis, vasospastic acrosyndrome, and arterio- venous thromboembolism. We speculated that in COVID-19, beyond the classical pulmonary immune-inflammation view, the occurrence of an oxygen-deprived blood disease, with iron metabolism dysregulation, should be taken in consideration. A more comprehensive diagnostic/therapeutic approach to COVID-19 is proposed, including potential adjuvant interventions aimed at improving hemoglobin dysfunction, iron over-deposit and generalized hypoxic state.
Keywords: COVID-19; hemoglobin; iron; hypoxia COVID-19; hemoglobin; iron; hypoxia

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MDPI and ACS Style

Cavezzi, A.; Troiani, E.; Corrao, S. COVID-19: Hemoglobin, Iron, and Hypoxia beyond Inflammation. A Narrative Review. Clin. Pract. 2020, 10, 1271.

AMA Style

Cavezzi A, Troiani E, Corrao S. COVID-19: Hemoglobin, Iron, and Hypoxia beyond Inflammation. A Narrative Review. Clinics and Practice. 2020; 10(2):1271.

Chicago/Turabian Style

Cavezzi, Attilio, Emidio Troiani, and Salvatore Corrao. 2020. "COVID-19: Hemoglobin, Iron, and Hypoxia beyond Inflammation. A Narrative Review" Clinics and Practice 10, no. 2: 1271.

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