Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab (HAM8101)
Autor: | Martin Becker, Frauke Hein, Andreas Bergmann, Dominik Jarczak, Mahir Karakas, Axel Nierhaus, Marc Lütgehetmann, Tim Philipp Simon, Stefan Kluge, Gernot Marx, Kevin Roedl, Marylyn M. Addo, Jens Zimmermann |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Adult
Male medicine.medical_specialty ARDS medicine.medical_treatment Critical Illness Adrecizumab Population Pneumonia Viral 030204 cardiovascular system & hematology Antibodies Monoclonal Humanized Biochemistry Procalcitonin Article law.invention Sepsis 03 medical and health sciences 0302 clinical medicine HAM 8101 endothelial function law Internal medicine Medicine Humans 030212 general & internal medicine Renal replacement therapy education Molecular Biology Pandemics Aged Mechanical ventilation education.field_of_study Respiratory Distress Syndrome business.industry COVID-19 Middle Aged medicine.disease Intensive care unit adrenomedullin SOFA score Female Endothelium Vascular business Coronavirus Infections |
Zdroj: | Biomolecules Volume 10 Issue 8 |
ISSN: | 2218-273X |
DOI: | 10.3390/biom10081171 |
Popis: | 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 &ldquo treatment on a named-patient basis&rdquo 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&ndash 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. |
Databáze: | OpenAIRE |
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