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
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.