Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial.
Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial.
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DOI：
10.1038/s41591-021-01488-2
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发表时间：
2021-11
期刊：
影响因子：
82.9
通讯作者：
Arnold DM
中科院分区：
文献类型：
--
作者：
Bégin P;Callum J;Jamula E;Cook R;Heddle NM;Tinmouth A;Zeller MP;Beaudoin-Bussières G;Amorim L;Bazin R;Loftsgard KC;Carl R;Chassé M;Cushing MM;Daneman N;Devine DV;Dumaresq J;Fergusson DA;Gabe C;Glesby MJ;Li N;Liu Y;McGeer A;Robitaille N;Sachais BS;Scales DC;Schwartz L;Shehata N;Turgeon AF;Wood H;Zarychanski R;Finzi A;CONCOR-1 Study Group;Arnold DM
恢复期血浆对2019冠状病毒病（COVID-19）的疗效尚不清楚。尽管大多数随机对照试验显示了阴性结果，但非对照研究表明抗体含量可能会影响患者的结局。我们对在呼吸道症状发作后12天内接受氧气治疗的COVID-19成年患者进行了一项开放标签、随机对照试验（NCT 04348656）。患者以2：1的比例分配至500 ml恢复期血浆或标准治疗。复合主要结局为插管或30天内死亡。通过逻辑回归分析评估恢复期血浆抗体对主要结局的影响。在达到无效停止标准后，试验在计划入组的78%时终止。共有940例患者接受随机化，921例患者纳入意向治疗分析。恢复期血浆组中199/614（32.4%）例患者和标准治疗组中86/307（28.0%）例患者发生插管或死亡-相对风险（RR）= 1.16（95%置信区间（CI）0.94-1.43，P = 0.18）。恢复期血浆治疗组患者的严重不良事件发生率更高（33.4% vs 26.4%; RR = 1.27，95%CI 1.02-1.57，P = 0.034）。抗体含量对恢复期血浆的疗效有显著的调节作用。在多变量分析中，中和或抗体依赖性细胞毒性的每个标准化对数增加独立地降低了血浆（比值比（OR）分别为0.74，95%CI 0.57-0.95和OR = 0.66，95%CI 0.50-0.87），而抗全跨膜刺突蛋白的IgG增加了其表达。（OR = 1.53，95%CI 1.14-2.05）。恢复期血浆并没有降低COVID-19住院患者30天插管或死亡的风险。与标准治疗相比，输注具有不利抗体谱的恢复期血浆可能与更差的临床结局相关。一项针对COVID-19住院患者的随机试验显示，使用恢复期血浆没有任何益处，反而可能增加危害，亚组分析表明，供体血浆中的抗体谱对确定临床结局至关重要。
The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care. A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.
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影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1016/j.xcrm.2021.100290
发表时间：
2021-06-15
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Anand SP;Prévost J;Nayrac M;Beaudoin-Bussières G;Benlarbi M;Gasser R;Brassard N;Laumaea A;Gong SY;Bourassa C;Brunet-Ratnasingham E;Medjahed H;Gendron-Lepage G;Goyette G;Gokool L;Morrisseau C;Bégin P;Martel-Laferrière V;Tremblay C;Richard J;Bazin R;Duerr R;Kaufmann DE;Finzi A
通讯作者：
Finzi A
影响因子：
2.9
作者：
Blackall, Douglas;Wulff, Shephali;Katz, Louis
通讯作者：
Katz, Louis
影响因子：
8
作者：
Abe, Kento T.;Li, Zhijie;Gingras, Anne-Claude
通讯作者：
Gingras, Anne-Claude
影响因子：
120.7
作者：
Li, Ling;Zhang, Wei;Liu, Zhong
通讯作者：
Liu, Zhong