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

Authors: Li, L, Zhang, W, Hu, Y, Tong, X, Zheng, S, Yang, J, Kong, Y, Ren, L, Wei, Q, Mei, H, Hu, C, Tao, C, Yang, R, Wang, J, Yu, Y, Guo, Y, Wu, X, Xu, Z, Zeng, L, Xiong, N, Chen, L, Wang, J, Man, N, Liu, Y, Xu, H, Deng, E., Zhang, X, Li, C, Wang, C, Su, S, Zhang, L, Wang, J, Wu, Y, and Liu, Z.

Publication: JAMA; May 2020

Affiliations: Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu, China; Key Laboratory of Transfusion AdverseReactions, CAMS, Chengdu, China; Guanggu District Maternal and Child Health Hospital of Hubei Province, Wuhan, China; Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, the Second Military Medical University, Shanghai, China; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Pulmonary and Critical Care Medicine, Beijing Hospital, National Respiratory quality control center, National Center of Gerontology, Beijing, China; Department of Transfusion, General Hospital of Central Theater Command of PLA, Wuhan, China; State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union, Beijing, China; NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Blood Transfusion, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Wuhan Red Cross Hospital, Wuhan, China; Department of Blood Transfusion, Wuhan Asia Heart Hospital, Wuhan, China ; Department of Blood Transfusion, Wuhan Asia General Hospital, Wuhan, China; Wuhan Blood Center, Wuhan, China; Peking University Clinical Research Institute, Peking University Health Science Center, Beijing, China; Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China (…); Department of Pathology, University of Miami, Miami, Florida.

Abstract: QUESTION: What is the effect of convalescent plasma therapy added to standard treatment, compared with standard treatment alone, on clinical outcomes in patients with severe or life-threatening coronavirus disease 2019 (COVID-19)? FINDING: In this randomized clinical trial that included 103 patients and was terminated early, the hazard ratio for time to clinical improvement within 28 days in the convalescent plasma group vs the standard treatment group was 1.40 and was not statistically significant. MEANING: Among patients with severe or life-threatening COVID-19, convalescent plasma therapy added to standard treatment did not significantly improve the time to clinical improvement within 28 days, although the trial was terminated early and may have been underpowered to detect a clinically important difference. 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 eventswithin 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. Trial Registration Chinese Clinical Trial Registry: ChiCTR2000029757.