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

1
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
2
Department of Intensive Care Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6500HB Nijmegen, The Netherlands
3
Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
4
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany
5
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; https://doi.org/10.3390/antiox9060540
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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