Recently, the stabilization of the endothelium has been explicitly identified as a therapeutic goal in coronavirus disease 2019 (COVID-19). Adrecizumab 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.

中文翻译：

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使用抗肾上腺髓质素抗体 Adrecizumab (HAM8101) 靶向 8 名 COVID-19 重症患者的内皮功能障碍。

最近，内皮的稳定已被明确确定为 2019 年冠状病毒病 (COVID-19) 的治疗目标。Adrecizumab 是一流的人源化单克隆抗肾上腺髓质素（抗 ADM）抗体，针对败血症和炎症的血管和毛细血管渗漏。在“基于指定患者的治疗”方法中，Adrecizumab 被用于八名患有急性呼吸窘迫综合征 (ARDS) 的重症 COVID-19 患者。患者接受单剂 Adrecizumab，在机械通气开始后 1 至 3 天给药。SOFA（中位数 12.5）和 SAPS-II（中位数 39）分数清楚地记录了风险最高的人群。此外，其中六名患者患有急性肾功能衰竭，其中五名需要进行肾脏替代治疗。随访时间为 13 至 27 天。Adrecizumab 给药后，低剂量组 1 名患者在第 4 天死于暴发性肺栓塞，4 人病情稳定，3 人从重症监护病房 (ICU) 出院。在 12 天内，7 名存活患者中有 5 名的 SOFA 评分和疾病严重程度评分（范围 0-16，反映 ICU 中的关键资源，评分越高表明病情越严重）下降（所有高-剂量患者）。PaO2/FiO2 在 12 天内增加，而炎症参数 C 反应蛋白、降钙素原和白细胞介素 6 下降。重要的是，死亡率低于预期并由 SOFA 评分计算得出。综上所述，在这个由 8 名危及生命的 COVID-19 和 ARDS 休克患者组成的初步不受控制的病例系列中，服用 Adrecizumab 后取得了良好的结果。尽管非对照设计和小样本量排除了关于 Adrecizumab 在危重 COVID-19 患者中潜在疗效的任何明确陈述，但该病例系列的结果令人鼓舞。