Department of Plastic Surgery, University Toulouse III Paul Sabatier, Toulouse, France; Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Vascularized Composite Allotransplantation Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States; Department of Plastic Surgery, European George Pompidou Hospital, University of Paris, Paris, France.
Med Hypotheses. 2021 Jan;146:110421. doi: 10.1016/j.mehy.2020.110421. Epub 2020 Nov 24.
Infection with SARS-CoV-2 is responsible for the COVID-19 crisis affecting the whole world. This virus can provoke acute respiratory distress syndrome (ARDS) leading to overcrowed the intensive care unit (ICU). Over the last months, worldwide experience demonstrated that the ARDS in COVID-19 patients are in many ways "atypical". The mortality rate in ventilated patients is high despite the application of the gold standard treatment (protective ventilation, curare, prone position, inhaled NO). Several studies suggested that the SARS-CoV-2 could interact negatively on red blood cell homeostasis. Furthermore, SarsCov2 creates Reactive Oxygen Species (ROS), which are toxic and generate endothelial dysfunction. Hypothesis/objective(s) We hypothesis that HEMO2Life® administrated intravenously is safe and could help symptomatically the patient condition. It would increase arterial oxygen content despite lung failure and allow better tissue oxygenation control. The use of HEMO2Life® is also interesting due to its anti-oxidative effect preventing cytokine storm induced by the SARS-CoV-2. Evaluation of the hypothesis: Hemarina is based on the properties of the hemoglobin of the Arenicola marina sea-worm (HEMO2Life®). This extracellular hemoglobin has an oxygen capacity 40 times greater than the hemoglobin of vertebrates. Furthermore, the size of this molecule is 250 times smaller than a human red blood cell, allowing it to diffuse in all areas of the microcirculation, without diffusing outside the vascular sector. It possesses an antioxidative property du a Superoxide Dismutase Activity. This technology has been the subject of numerous publications and HEMO2Life® was found to be well-tolerated and did not induce toxicity. It was administered intravenously to hamsters and rats, and showed no acute effect on heart rate and blood pressure and did not cause microvascular vasoconstriction. In preclinical in vivo models (mice, rats, and dogs), HEMO2Life® has enabled better tissue oxygenation, especially in the brain. This molecule has already been used in humans in organ preservation solutions and the patients showed no abnormal clinical signs.
The expected benefits of HEMO2Life® for COVID-19 patients are improved survival, avoidance of tracheal intubation, shorter oxygen supplementation, and the possibility of treating a larger number of patients as molecular respirator without to use an invasive machine.
感染 SARS-CoV-2 是导致全球 COVID-19 危机的原因。这种病毒可引起急性呼吸窘迫综合征(ARDS),导致重症监护病房(ICU)人满为患。在过去的几个月中,全球经验表明,COVID-19 患者的 ARDS 在许多方面都是“非典型的”。尽管采用了金标准治疗(保护性通气、肌松剂、俯卧位、吸入一氧化氮),但通气患者的死亡率仍然很高。几项研究表明,SARS-CoV-2 可能对红细胞内稳态产生负面影响。此外,SarsCov2 会产生活性氧(ROS),这些物质有毒,会导致内皮功能障碍。
假设/目的:我们假设静脉内给予 HEMO2Life®是安全的,并可以帮助患者的症状。它可以增加动脉血氧含量,尽管有肺衰竭,但可以更好地控制组织氧合。由于其抗氧化作用,可以防止 SARS-CoV-2 引起的细胞因子风暴,因此使用 HEMO2Life®也很有趣。
Hemarina 基于 Arenicola marina 海虫(HEMO2Life®)血红蛋白的特性。这种细胞外血红蛋白的氧容量比脊椎动物的血红蛋白高 40 倍。此外,这种分子的大小比人类红细胞小 250 倍,因此可以扩散到微循环的所有区域,而不会扩散到血管区域之外。它具有抗氧化特性,因为具有超氧化物歧化酶活性。这项技术已经有很多出版物,HEMO2Life®被发现耐受性良好,没有毒性。它被静脉内给予仓鼠和大鼠,没有对心率和血压产生急性影响,也没有引起微血管血管收缩。在临床前体内模型(小鼠、大鼠和狗)中,HEMO2Life®能够更好地改善组织氧合,特别是在大脑中。这种分子已经在器官保存溶液中用于人类,患者没有出现异常的临床症状。
HEMO2Life®对 COVID-19 患者的预期益处是提高生存率,避免气管插管,缩短氧疗时间,并有可能治疗更多的患者,作为分子呼吸机,而无需使用有创机器。