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.