中国医学科学院刘忠团队探讨了恢复期血浆疗效治疗危重症COVID-19患者的临床效果。2020年6月3日，该成果发表在《美国医学会杂志》上。

对于COVID-19患者，恢复期血浆是一种潜在的治疗选择，但需要随机临床试验进行验证。为了评估恢复期血浆治疗COVID-19患者的疗效和不良反应， 2020年2月14日至4月1日，研究组在武汉的7个医疗中心进行了一项开放标签、多中心、随机临床试验，招募了103名实验室确诊的COVID-19重症或危重患者。根据疾病严重程度，52例患者接受恢复期血浆+标准治疗，51例患者仅接受标准治疗。主要结局是在28天之内达到临床改善的时间，定义为患者活着出院或疾病严重程度评分减少2分。

103例患者的中位年龄为70岁，男性占58.3%，有101例（98.1%）患者完成了试验。恢复期血浆组中有51.9%的患者在28天内发生临床改善，对照组为43.1%，风险比为1.40。恢复期血浆组的重症患者中有91.3%发生主要结局，对照组为68.2%，风险比为2.15；恢复期血浆组的危重症患者中有20.7%发生主要结局，对照组为24.1%。

恢复期血浆组的28天死亡率为15.7%，对照组为24.0%，差异不显著；第28天的出院率为51.0%，对照组为36.0%，差异不显著。恢复期血浆组中有87.2%的患者在72小时内病毒PCR转阴，显著高于对照组（37.5%）。恢复期血浆组中有两名患者在输血后数小时内经历了不良事件，并在支持治疗下得到改善。

总之，在重症或危重COVID-19患者中，与单独的标准治疗相比，标准治疗联合恢复期血浆疗法在28天内并不能显著提高临床改善率。

附：英文原文

Title: Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial

Author: Ling Li, Wei Zhang, Yu Hu, Xunliang Tong, Shangen Zheng, Juntao Yang, Yujie Kong, Lili Ren, Qing Wei, Heng Mei, Caiying Hu, Cuihua Tao, Ru Yang, Jue Wang, Yongpei Yu, Yong Guo, Xiaoxiong Wu, Zhihua Xu, Li Zeng, Nian Xiong, Lifeng Chen, Juan Wang, Ning Man, Yu Liu, Haixia Xu, E. Deng, Xuejun Zhang, Chenyue Li, Conghui Wang, Shisheng Su, Linqi Zhang, Jianwei Wang, Yanyun Wu, Zhong Liu

Issue&Volume: 2020-06-03

Abstract: Importance  Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19), but further data from randomized clinical trials are needed.

Objective  To evaluate the efficacy and adverse effects of convalescent plasma therapy for patients with COVID-19.

Design, Setting, and Participants  Open-label, multicenter, randomized clinical trial performed in 7 medical centers in Wuhan, China, from February 14, 2020, to April 1, 2020, with final follow-up April 28, 2020. The trial included 103 participants with laboratory-confirmed COVID-19 that was severe (respiratory distress and/or hypoxemia) or life-threatening (shock, organ failure, or requiring mechanical ventilation). The trial was terminated early after 103 of a planned 200 patients were enrolled.

Intervention  Convalescent plasma in addition to standard treatment (n=52) vs standard treatment alone (control) (n=51), stratified by disease severity.

Main Outcomes and Measures  Primary outcome was time to clinical improvement within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale (ranging from 1 [discharge] to 6 [death]). Secondary outcomes included 28-day mortality, time to discharge, and the rate of viral polymerase chain reaction (PCR) results turned from positive at baseline to negative at up to 72 hours.

Results  Of 103 patients who were randomized (median age, 70 years; 60 [58.3%] male), 101 (98.1%) completed the trial. Clinical improvement occurred within 28 days in 51.9% (27/52) of the convalescent plasma group vs 43.1% (22/51) in the control group (difference, 8.8% [95% CI, 10.4% to 28.0%]; hazard ratio [HR], 1.40 [95% CI, 0.79-2.49]; P=.26). Among those with severe disease, the primary outcome occurred in 91.3% (21/23) of the convalescent plasma group vs 68.2% (15/22) of the control group (HR, 2.15 [95% CI, 1.07-4.32]; P=.03); among those with life-threatening disease the primary outcome occurred in 20.7% (6/29) of the convalescent plasma group vs 24.1% (7/29) of the control group (HR, 0.88 [95% CI, 0.30-2.63]; P=.83) (P for interaction=.17). There was no significant difference in 28-day mortality (15.7% vs 24.0%; OR, 0.65 [95% CI, 0.29-1.46]; P=.30) or time from randomization to discharge (51.0% vs 36.0% discharged by day 28; HR, 1.61 [95% CI, 0.88-2.93]; P=.12). Convalescent plasma treatment was associated with a negative conversion rate of viral PCR at 72 hours in 87.2% of the convalescent plasma group vs 37.5% of the control group (OR, 11.39 [95% CI, 3.91-33.18]; P<.001). Two patients in the convalescent plasma group experienced adverse events within hours after transfusion that improved with supportive care.

Conclusion and Relevance  Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment, compared with standard treatment alone, did not result in a statistically significant improvement in time to clinical improvement within 28 days. Interpretation is limited by early termination of the trial, which may have been underpowered to detect a clinically important difference.

DOI: 10.1001/jama.2020.10044

Source: https://jamanetwork.com/journals/jama/article-abstract/2766943