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Article

Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab (HAM8101)

1
German Center for Cardiovascular Research (DZHK), Partner Site Hamburg-Kiel-Lübeck, 20251 Hamburg, Germany
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Department of Cardiology, University Heart & Vascular Center Hamburg, 20251 Hamburg, Germany
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Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
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Division of Infectious Diseases, First Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
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Department of Clinical Immunology of Infectious Diseases, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany
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German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, 20359 Hamburg, Germany
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Adrenomed AG, 16761 Hennigsdorf, Germany
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SphingoTec GmbH, 16761 Hennigsdorf, Germany
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4TEEN4 Pharmaceuticals GmbH, 16761 Hennigsdorf, Germany
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Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, 52074 Aachen, Germany
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Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
*
Author to whom correspondence should be addressed.
Biomolecules 2020, 10(8), 1171; https://doi.org/10.3390/biom10081171
Received: 16 June 2020 / Revised: 6 August 2020 / Accepted: 10 August 2020 / Published: 11 August 2020
(This article belongs to the Special Issue Biomolecules for Translational Approaches in Cardiology)
Recently, the stabilization of the endothelium has been explicitly identified as a therapeutic goal in coronavirus disease 2019 (COVID-19). Adrecizumab (HAM8101) is a first-in-class humanized monoclonal anti-Adrenomedullin (anti-ADM) antibody, targeting the sepsis- and inflammation-based vascular and capillary leakage. Within a “treatment on a named-patient basis” approach, Adrecizumab was administered to eight extreme-critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). The patients received a single dose of Adrecizumab, which was administered between 1 and 3 days after the initiation of mechanical ventilation. The SOFA (median 12.5) and SAPS-II (median 39) scores clearly documented the population at highest risk. Moreover, six of the patients suffered from acute renal failure, of whom five needed renal replacement therapy. The length of follow-up ranged between 13 and 27 days. Following the Adrecizumab administration, one patient in the low-dose group died at day 4 due to fulminant pulmonary embolism, while four were in stable condition, and three were discharged from the intensive care unit (ICU). Within 12 days, the SOFA score, as well as the disease severity score (range 0–16, mirroring critical resources in the ICU, with higher scores indicating more severe illness), decreased in five out of the seven surviving patients (in all high-dose patients). The PaO2/FiO2 increased within 12 days, while the inflammatory parameters C-reactive protein, procalcitonin, and interleukin-6 decreased. Importantly, the mortality was lower than expected and calculated by the SOFA score. In conclusion, in this preliminary uncontrolled case series of eight shock patients with life-threatening COVID-19 and ARDS, the administration of Adrecizumab was followed by a favorable outcome. Although the non-controlled design and the small sample size preclude any definitive statement about the potential efficacy of Adrecizumab in critically ill COVID-19 patients, the results of this case series are encouraging. View Full-Text
Keywords: COVID-19; Adrecizumab; HAM 8101; adrenomedullin; endothelial function COVID-19; Adrecizumab; HAM 8101; adrenomedullin; endothelial function
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MDPI and ACS Style

Karakas, M.; Jarczak, D.; Becker, M.; Roedl, K.; Addo, M.M.; Hein, F.; Bergmann, A.; Zimmermann, J.; Simon, T.-P.; Marx, G.; Lütgehetmann, M.; Nierhaus, A.; Kluge, S. Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab (HAM8101). Biomolecules 2020, 10, 1171. https://doi.org/10.3390/biom10081171

AMA Style

Karakas M, Jarczak D, Becker M, Roedl K, Addo MM, Hein F, Bergmann A, Zimmermann J, Simon T-P, Marx G, Lütgehetmann M, Nierhaus A, Kluge S. Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab (HAM8101). Biomolecules. 2020; 10(8):1171. https://doi.org/10.3390/biom10081171

Chicago/Turabian Style

Karakas, Mahir, Dominik Jarczak, Martin Becker, Kevin Roedl, Marylyn M. Addo, Frauke Hein, Andreas Bergmann, Jens Zimmermann, Tim-Philipp Simon, Gernot Marx, Marc Lütgehetmann, Axel Nierhaus, and Stefan Kluge. 2020. "Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab (HAM8101)" Biomolecules 10, no. 8: 1171. https://doi.org/10.3390/biom10081171

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