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Targeting the Heme-Heme Oxygenase System to Prevent Severe Complications Following COVID-19 Infections

Department of Dentistry-Orthodontics and Craniofacial Biology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Philips van Leydenlaan 25, 6525EX Nijmegen, The Netherlands
Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500HB Nijmegen, The Netherlands
Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany
Departments of Medicine and Pharmacology, New York Medical College, Valhalla, NY 10595, USA
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(6), 540;
Received: 28 May 2020 / Revised: 15 June 2020 / Accepted: 16 June 2020 / Published: 19 June 2020
(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1)
SARS-CoV-2 is causing a pandemic resulting in high morbidity and mortality. COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) are often critically ill and show lung injury and hemolysis. Heme is a prosthetic moiety crucial for the function of a wide variety of heme-proteins, including hemoglobin and cytochromes. However, injury-derived free heme promotes adhesion molecule expression, leukocyte recruitment, vascular permeabilization, platelet activation, complement activation, thrombosis, and fibrosis. Heme can be degraded by the anti-inflammatory enzyme heme oxygenase (HO) generating biliverdin/bilirubin, iron/ferritin, and carbon monoxide. We therefore postulate that free heme contributes to many of the inflammatory phenomena witnessed in critically ill COVID-19 patients, whilst induction of HO-1 or harnessing heme may provide protection. HO-activity not only degrades injurious heme, but its effector molecules possess also potent salutary anti-oxidative and anti-inflammatory properties. Until a vaccine against SARS-CoV-2 becomes available, we need to explore novel strategies to attenuate the pro-inflammatory, pro-thrombotic, and pro-fibrotic consequences of SARS-CoV-2 leading to morbidity and mortality. The heme-HO system represents an interesting target for novel “proof of concept” studies in the context of COVID-19. View Full-Text
Keywords: heme; heme oxygenase; SARS-CoV-2; inflammation; COVID-19 heme; heme oxygenase; SARS-CoV-2; inflammation; COVID-19
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Wagener, F.A.D.T.G.; Pickkers, P.; Peterson, S.J.; Immenschuh, S.; Abraham, N.G. Targeting the Heme-Heme Oxygenase System to Prevent Severe Complications Following COVID-19 Infections. Antioxidants 2020, 9, 540.

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