{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:17:13Z","timestamp":1791256633799,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T00:00:00Z","timestamp":1590624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinics and Practice"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.4081\/cp.2020.1271","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T05:06:46Z","timestamp":1590642406000},"page":"1271","source":"Crossref","is-referenced-by-count":348,"title":["COVID-19: Hemoglobin, Iron, and Hypoxia beyond Inflammation. A Narrative Review"],"prefix":"10.3390","volume":"10","author":[{"given":"Attilio","family":"Cavezzi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emidio","family":"Troiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Corrao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,28]]},"reference":[{"issue":"20","key":"ref1","first-page":"35008","article-title":"COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up (Epub 2020 Apr 15)","volume":"S0735-1097","author":"Bikdeli","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"100618","DOI":"10.1016\/j.cpcardiol.2020.100618","article-title":"COVID-19 and multiorgan response (Epub 2020 Apr 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