Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.
Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults.
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DOI：
10.1056/nejmoa2033700
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发表时间：
2021-02-18
期刊：
影响因子：
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通讯作者：
Fundación INFANT–COVID-19 Group
中科院分区：
文献类型：
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作者：
Libster R;Pérez Marc G;Wappner D;Coviello S;Bianchi A;Braem V;Esteban I;Caballero MT;Wood C;Berrueta M;Rondan A;Lescano G;Cruz P;Ritou Y;Fernández Viña V;Álvarez Paggi D;Esperante S;Ferreti A;Ofman G;Ciganda Á;Rodriguez R;Lantos J;Valentini R;Itcovici N;Hintze A;Oyarvide ML;Etchegaray C;Neira A;Name I;Alfonso J;López Castelo R;Caruso G;Rapelius S;Alvez F;Etchenique F;Dimase F;Alvarez D;Aranda SS;Sánchez Yanotti C;De Luca J;Jares Baglivo S;Laudanno S;Nowogrodzki F;Larrea R;Silveyra M;Leberzstein G;Debonis A;Molinos J;González M;Perez E;Kreplak N;Pastor Argüello S;Gibbons L;Althabe F;Bergel E;Polack FP;Fundación INFANT–COVID-19 Group
阻断2019冠状病毒病（Covid-19）早期进展的疗法仍然难以捉摸。其中，向住院患者施用恢复期血浆一直不成功，可能是因为抗体应在疾病过程中较早施用。我们进行了一项随机、双盲、安慰剂对照试验，在老年患者中，在轻度Covid-19症状发作后72小时内，使用针对严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的高IgG滴度恢复期血浆。主要终点是严重呼吸系统疾病，定义为呼吸频率为每分钟30次或以上，患者呼吸环境空气时氧饱和度低于93%，或两者兼而有之。试验在预计样本量的76%时提前停止，因为试验地区的Covid-19病例大幅减少，试验患者的稳定入组几乎不可能。共160例患者接受了随机化。在意向治疗人群中，80例接受恢复期血浆治疗的患者中有13例（16%）发生严重呼吸道疾病，80例接受安慰剂治疗的患者中有25例（31%）发生严重呼吸道疾病（相对风险，0.52; 95%置信区间[CI]，0.29 - 0.94; P=0.03），相对风险降低48%。一项改良的意向治疗分析排除了6例在输注恢复期血浆或安慰剂前发生主要终点事件的患者，结果显示效应量更大（相对风险，0.40; 95%CI，0.20 - 0.81）。未观察到征集性不良事件。早期给予轻度感染的老年人抗SARS-CoV-2的高滴度恢复期血浆可减缓Covid-19的进展。（由比尔和梅林达·盖茨基金会和婴儿大流行病基金会资助; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud编号，PAEPCC 19，Plataforma de Registro Informatizado de Investigaciones en Salud编号，1421和ClinicalTrials.gov编号，NCT 04479163。
Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness. We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible. A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P=0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed. Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163.)