Lopardo Gustavo, Belloso Waldo H, Nannini Esteban, Colonna Mariana, Sanguineti Santiago, Zylberman Vanesa, Muñoz Luciana, Dobarro Martín, Lebersztein Gabriel, Farina Javier, Vidiella Gabriela, Bertetti Anselmo, Crudo Favio, Alzogaray Maria Fernanda, Barcelona Laura, Teijeiro Ricardo, Lambert Sandra, Scublinsky Darío, Iacono Marisa, Stanek Vanina, Solari Rubén, Cruz Pablo, Casas Marcelo Martín, Abusamra Lorena, Luciardi Héctor Lucas, Cremona Alberto, Caruso Diego, de Miguel Bernardo, Lloret Santiago Perez, Millán Susana, Kilstein Yael, Pereiro Ana, Sued Omar, Cahn Pedro, Spatz Linus, Goldbaum Fernando
Hospital Municipal Dr. Bernardo Houssay, Pte Hipólito Yrigoyen 1757, Florida, Provincia de Buenos Aires, Argentina.
Fundación del Centro de Estudios Infectológicos (FUNCEI), French 3085, Ciudad Autónoma de Buenos Aires, Buenos Aires C1425, Argentina.
EClinicalMedicine. 2021 Apr;34:100843. doi: 10.1016/j.eclinm.2021.100843. Epub 2021 Apr 11.
passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2.
we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984).
between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 ( = 118) or placebo ( = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported.
Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.
被动免疫疗法是治疗新型冠状病毒肺炎（COVID-19）患者的一种替代疗法。马多克隆抗体（EpAbs）可能是一种可扩展的针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的中和抗体来源。
我们进行了一项双盲、随机、安慰剂对照试验，以评估EpAbs（INM005）在阿根廷19家医院住院的中重度COVID-19肺炎成年患者中的疗效和安全性。主要终点是在第28天或出院时世界卫生组织（WHO）序贯临床量表中至少两个类别得到改善（ClinicalTrials.gov编号NCT04494984）。
在2020年8月1日至10月26日期间，共招募了245名患者。入选患者被分配接受两剂盲法的INM005（n = 118）或安慰剂（n = 123）。中位年龄为54岁，65.1%为男性，61%在基线时患有中度疾病。从症状出现到研究治疗的中位时间为6天（四分位间距为5至8天）。在主要终点方面，研究组之间未观察到统计学上的显著差异（风险差异[95%置信区间]：5.28%[-3.95；14.50]；P = 0.15）。在随访的第14天和第21天，INM005组至少两个类别得到改善的比例在统计学上显著更高。INM005组达到两个序贯类别改善或出院的时间为14.2（±0.7）天，安慰剂组为16.3（±0.7）天，风险比为1.31（95%置信区间为1.0至1.74）。亚组分析显示INM005对重症患者和基线抗体阴性的患者有有益作用。INM005组的总死亡率为6.9%，安慰剂组为11.4%（风险差异[95%置信区间]：0.57[0.24至1.37]）。特别关注的不良事件为轻度或中度；未报告过敏反应。
尽管未达到主要终点，但我们发现SARS-CoV-2肺炎住院患者的临床症状有所改善，尤其是重症患者。
