Temesgen Zelalem, Assi Mariam, Vergidis Paschalis, Rizza Stacey A, Bauer Philippe R, Pickering Brian W, Razonable Raymund R, Libertin Claudia R, Burger Charles D, Orenstein Robert, Vargas Hugo E, Varatharaj Palraj Bharath Raj, Dababneh Ala S, Chappell Gabrielle, Chappell Dale, Ahmed Omar, Sakemura Reona, Durrant Cameron, Kenderian Saad S, Badley Andrew
medRxiv. 2020 Jun 14:2020.06.08.20125369. doi: 10.1101/2020.06.08.20125369.
In COVID-19, high levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and inflammatory myeloid cells correlate with disease severity, cytokine storm, and respiratory failure. With this rationale, we used lenzilumab, an anti-human GM-CSF monoclonal antibody, to treat patients with severe COVID-19 pneumonia.
Hospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use IND application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. All patients receiving lenzilumab through May 1, 2020 were included in this report.
Twelve patients were treated with lenzilumab. Clinical improvement was observed in 11 out of 12 (92%), with a median time to discharge of 5 days. There was a significant improvement in oxygenation: The proportion of patients with SpO2/FiO2 < 315 at the end of observation was 8% vs. compared to 67% at baseline (p=0.00015). A significant improvement in mean CRP and IL-6 values on day 3 following lenzilumab administration was also observed (137.3 mg/L vs 51.2 mg/L, p = 0.040; 26.8 pg/mL vs 16.1 pg/mL, p = 0.035; respectively). Cytokine analysis showed a reduction in inflammatory myeloid cells two days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab, and no mortality in this cohort of patients with severe COVID-19 pneumonia.
In high-risk COVID-19 patients with severe pneumonia, GM-CSF neutralization with lenzilumab was safe and associated with improved clinical outcomes, oxygen requirement, and cytokine storm.
在新型冠状病毒肺炎（COVID-19）中，高水平的粒细胞巨噬细胞集落刺激因子（GM-CSF）和炎性髓系细胞与疾病严重程度、细胞因子风暴及呼吸衰竭相关。基于这一理论依据，我们使用抗人GM-CSF单克隆抗体伦齐单抗治疗重症COVID-19肺炎患者。
通过紧急一次性研究性新药申请，对住院的COVID-19肺炎患者及预后不良风险因素患者静脉注射600 mg伦齐单抗，共三剂。记录患者特征、临床和实验室结果以及不良事件。本报告纳入了截至2020年5月1日接受伦齐单抗治疗的所有患者。
12例患者接受了伦齐单抗治疗。12例中有11例（92%）临床症状改善，出院中位时间为5天。氧合情况有显著改善：观察期末动脉血氧分压/吸入氧浓度（SpO2/FiO2）<315的患者比例为8%，而基线时为67%（p=0.00015）。在给予伦齐单抗后第3天，还观察到平均C反应蛋白（CRP）和白细胞介素-6（IL-6）值有显著改善（分别为137.3 mg/L对51.2 mg/L，p = 0.040；26.8 pg/mL对16.1 pg/mL，p = 0.035）。细胞因子分析显示，伦齐单抗治疗两天后炎性髓系细胞减少。该队列中没有因伦齐单抗导致的治疗中出现的不良事件，且重症COVID-19肺炎患者无死亡病例。
在患有重症肺炎的高危COVID-19患者中，使用伦齐单抗中和GM-CSF是安全的，且与临床结果改善、氧需求降低及细胞因子风暴缓解相关。
