恢复期血浆疗法治疗重症 COVID-19 患者的疗效。

Effectiveness of convalescent plasma therapy in severe COVID-19 patients.

机构信息

China National Biotec Group Company Limited, 100029 Beijing, China.

National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd., 430207 Wuhan, China.

出版信息

Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9490-9496. doi: 10.1073/pnas.2004168117. Epub 2020 Apr 6.

Abstract

Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 10/L vs. 0.76 × 10/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials.

摘要

目前,尚无针对 2019 年新型冠状病毒病(COVID-19)的批准的特效抗病毒药物。在本研究中,前瞻性纳入了 10 例经实时病毒 RNA 检测确诊的重症患者。给每位患者输注 1 次剂量为 200mL 的来自近期康复、中和抗体滴度≥1:640 的恢复期血浆(CP),作为最大程度支持治疗和抗病毒药物的补充。主要终点为 CP 输注的安全性。次要终点为 CP 输注后 3d 内临床症状和实验室参数的改善情况。从发病到 CP 输注的中位时间为 16.5d。CP 输注后,5 例患者的中和抗体水平迅速上升至 1:640,而另外 4 例患者的水平维持在较高水平(1:640)。CP 输注后 3d 内,临床症状随着血氧饱和度的升高而明显改善。与输注前相比,多项参数均有改善趋势,包括淋巴细胞计数增加(0.65×10/L 比 0.76×10/L)和 C 反应蛋白降低(55.98mg/L 比 18.13mg/L)。7d 内肺部病变的影像学检查显示不同程度的吸收。7 例之前有病毒血症的患者在输注后病毒载量不可检测。未观察到严重不良反应。本研究表明 CP 治疗具有良好的耐受性,通过中和重症 COVID-19 患者的病毒血症,可能改善临床结局。CP 治疗的最佳剂量和时间点以及临床获益还需要在更大规模的对照试验中进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fadb/7196837/6615a5c8a884/pnas.2004168117fig01.jpg

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