Song Alice T W, Rocha Vanderson, Mendrone-Júnior Alfredo, Calado Rodrigo T, De Santis Gil C, Benites Bruno D, Costa-Lima Carolina, Vargas Taiani, Marques Leonardo S, Fernandes Juliana C, Breda Felipe C, Wendel Silvano, Fachini Roberta, Rizzo Luiz V, Kutner José Mauro, Avelino-Silva Vivian I, Machado Rafael R G, Durigon Edison L, Chevret Sylvie, Kallas Esper G
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Fundação Pro Sangue Hemocentro de São Paulo, São Paulo, Brazil.
Lancet Reg Health Am. 2022 Jun;10:100216. doi: 10.1016/j.lana.2022.100216. Epub 2022 Mar 15.
Administration of convalescent plasma may serve as an adjunct to supportive treatment to prevent COVID-19 progression and death. We aimed to evaluate the efficacy and safety of 2 volumes of intravenous convalescent plasma (CP) with high antibody titers for the treatment of severe cases of COVID-19.
We conducted a Bayesian, randomized, open-label, multicenter, controlled clinical trial in 7 Brazilian hospitals. Adults admitted to hospital with positive RT-PCR for SARS-CoV2, within 10 days of the symptom onset, were eligible. Patients were randomly assigned (1:1:1) to receive standard of care (SoC) alone, or in combination with 200 mL (150-300 mL) of CP (Low-volume), or 400 mL (300-600 mL) of CP (High-volume); infusion had to be performed within 24 h of randomization. Randomization was centralized, stratified by center. The primary outcome was the time until clinical improvement up to day 28, measured by the WHO ten-point scale, assessed in the intention-to-treat population. Interim and terminal analyses were performed in a Bayesian framework. Trial registered at ClinicalTrials.gov: NCT04415086.
Between June 2, 2020, and November 18, 2020, 129 patients were enrolled and randomly assigned to SoC ( = 42), Low-volume ( = 43) or High-volume ( = 44) CP. Donors presented a median titer of neutralizing antibodies of 1:320 (interquartile range, 1:160 to 1:1088). No evidence of any benefit of convalescent plasma was observed, with Bayesian estimate of 28-day clinical improvement of 72.7% (95%CI, 58.8 to 84.7) in the SoC versus 64.1% (95%ci, 53.8 to 73.7) in the pooled experimental groups (mean difference of -8.7%, 95%CI, -24.6 to 8.2). There was one case of cutaneous mild allergic reaction related to plasma transfusion and one case of suspected transfusion-related acute lung injury but deemed not to be related to convalescent plasma infusion.
In this prospective, randomized trial of adult hospitalized patients with severe COVID-19, convalescent plasma was not associated with clinical benefits.
Brazilian Ministry of Science, Technology and Innovation, Fundação de Amparo à Pesquisa do Estado de São Paulo.
输注康复期血浆可作为支持性治疗的辅助手段，以预防新冠病毒病（COVID-19）病情进展和死亡。我们旨在评估两剂高抗体滴度静脉注射康复期血浆（CP）治疗重症COVID-19的疗效和安全性。
我们在巴西7家医院开展了一项贝叶斯随机开放标签多中心对照临床试验。症状出现10天内SARS-CoV2逆转录聚合酶链反应（RT-PCR）呈阳性且入院的成年人符合条件。患者被随机分配（1:1:1），分别单独接受标准治疗（SoC），或联合200毫升（150 - 300毫升）CP（低剂量组），或400毫升（300 - 600毫升）CP（高剂量组）；输注必须在随机分组后24小时内进行。随机分组采用集中式，按中心分层。主要结局是至第28天临床改善的时间，采用世界卫生组织十点量表进行测量，在意向性分析人群中进行评估。中期分析和最终分析均在贝叶斯框架下进行。该试验已在ClinicalTrials.gov注册：NCT04415086。
2020年6月2日至2020年11月18日期间，129例患者入组并随机分配至SoC组（n = 42）、低剂量CP组（n = 43）或高剂量CP组（n = 44）。供体的中和抗体滴度中位数为1:320（四分位间距，1:160至1:1088）。未观察到康复期血浆有任何益处的证据，贝叶斯估计SoC组第28天临床改善率为72.7%（95%CI，58.8至84.7），而合并实验组为64.1%（95%CI, 53.8至73.7）（平均差异为-8.7%，95%CI，-24.6至8.2）。有1例与输血相关的皮肤轻度过敏反应，1例疑似输血相关急性肺损伤，但认为与康复期血浆输注无关。
在这项针对成年重症COVID-19住院患者的前瞻性随机试验中，康复期血浆未显示出临床益处。
巴西科学、技术和创新部，圣保罗州研究资助基金会。
