Department of Infectious Diseases, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Internal Medicine, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
PLoS Med. 2021 Mar 3;18(3):e1003415. doi: 10.1371/journal.pmed.1003415. eCollection 2021 Mar.
Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression.
The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group) versus no CP unless developing prespecified criteria of deterioration (deferred plasma group). Additional standard treatment was allowed in both arms. The primary outcome was a composite of mechanical ventilation, hospitalization for >14 days, or death. The key secondary outcomes included time to respiratory failure, days of mechanical ventilation, hospital length of stay, mortality at 30 days, and SARS-CoV-2 real-time PCR clearance rate. Of 58 randomized patients (mean age, 65.8 years; 50% male), 57 (98.3%) completed the trial. A total of 13 (43.3%) participants from the deferred group received plasma based on clinical aggravation. We failed to find benefit in the primary outcome (32.1% versus 33.3%, odds ratio [OR] 0.95, 95% CI 0.32-2.84, p > 0.999) in the early versus deferred CP group. The in-hospital mortality rate was 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17 p = 0.246), mechanical ventilation 17.9% versus 6.7% (OR 3.04, 95% CI 0.54-17.17, p = 0.246), and prolonged hospitalization 21.4% versus 30.0% (OR 0.64, 95% CI, 0.19-2.10, p = 0.554) in the early versus deferred CP group, respectively. The viral clearance rate on day 3 (26% versus 8%, p = 0.204) and day 7 (38% versus 19%, p = 0.374) did not differ between groups. Two patients experienced serious adverse events within 6 hours after plasma transfusion. The main limitation of this study is the lack of statistical power to detect a smaller but clinically relevant therapeutic effect of CP, as well as not having confirmed neutralizing antibodies in donor before plasma infusion.
In the present study, we failed to find evidence of benefit in mortality, length of hospitalization, or mechanical ventilation requirement by immediate addition of CP therapy in the early stages of COVID-19 compared to its use only in case of patient deterioration.
NCT04375098.
尽管关于恢复期血浆（CP）疗效的证据有限，但作为 COVID-19 住院患者的同情治疗，CP 仍被广泛应用。我们旨在评估 COVID-19 进展过程中早期 CP 治疗的疗效和安全性。
本研究是在智利圣地亚哥的一家学术医疗中心进行的一项开放标签、单中心随机临床试验，于 2020 年 5 月 10 日至 2020 年 7 月 18 日进行，最终随访截至 2020 年 8 月 17 日。试验纳入了 COVID-19 症状出现后 7 天内住院，存在疾病进展风险因素且未进行机械通气的患者。干预措施包括立即给予 CP（早期血浆组）或仅在出现特定恶化标准时给予 CP（延迟血浆组）。两组均允许给予额外的标准治疗。主要结局是机械通气、住院>14 天或死亡的复合结局。关键次要结局包括呼吸衰竭时间、机械通气天数、住院时间、30 天死亡率和 SARS-CoV-2 实时 PCR 清除率。58 例随机患者（平均年龄 65.8 岁；50%为男性）中，57 例（98.3%）完成了试验。共有 13 名（43.3%）延迟组患者因临床恶化接受了血浆治疗。与延迟 CP 组相比，早期 CP 组在主要结局方面并未发现获益（32.1% vs. 33.3%，比值比 [OR] 0.95，95%置信区间 [CI] 0.32-2.84，p>0.999）。住院死亡率分别为 17.9% vs. 6.7%（OR 3.04，95% CI 0.54-17.17，p=0.246）、机械通气率分别为 17.9% vs. 6.7%（OR 3.04，95% CI 0.54-17.17，p=0.246）和延长住院时间率分别为 21.4% vs. 30.0%（OR 0.64，95% CI 0.19-2.10，p=0.554）。第 3 天（26% vs. 8%，p=0.204）和第 7 天（38% vs. 19%，p=0.374）的病毒清除率在两组间无差异。两名患者在血浆输注后 6 小时内出现严重不良事件。本研究的主要局限性是缺乏统计学效能来检测 CP 在 COVID-19 早期阶段治疗的较小但具有临床意义的疗效，并且在输注血浆前未确认供体中是否存在中和抗体。
与仅在患者恶化时使用相比，在 COVID-19 早期阶段立即添加 CP 治疗未能发现死亡率、住院时间或机械通气需求方面的获益。
NCT04375098。
