Chen Shanshan, Lu Chunya, Li Ping, Wang Lei, Wang Huaqi, Yang Qiankun, Chen-Li Yinghui, Li Jianbin, Ma Hongwei, Sang Qian, Xu Luyang, Li Jing, Zhang Yi, Kang Yi, Xing Lihua, Zhang Guojun
Department of Respiratory Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Department of Blood Transfusion, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020 Nov;32(11):1293-1298. doi: 10.3760/cma.j.cn121430-20200810-00568.
To evaluate the effectiveness and safety of convalescent plasma therapy in patients with severe and critical coronavirus disease 2019 (COVID-19).
Plasma of 200-400 mL was collected from convalescent patients 2 weeks after being discharged from the hospital. After viral nucleic acid testing and antibody testing, the plasma was infused into 16 severe or critical COVID-19 patients. Time for viral nucleic acid amplification (NAA) test turning negative, total volume of plasma transfusion, average antibody concentration, and total antibody amount were recorded. White blood cell (WBC) counts, lymphocyte (LYM) counts, neutrophil (NEU) counts, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB), hypersensitive cardiac troponin T (hs-cTnT), and lactic acid (Lac) levels were measured and the rate of change was calculated at the baseline (d0) before plasma transfusion, and day 1 (d1), day 3 (d3) after transfusion.
(1) Patient characteristics: among the 16 patients, 5 cases (31.25%) were severe COVID-19, and 11 cases (68.75%) were critical COVID-19; 62.50% (10/16) of the patients had primary disease; the percentage of invasive ventilation and use of extracorporeal membrane pulmonary oxygenation (ECMO) in critical patients were 90.91% (10/11) and 45.46% (5/11) respectively. (2) Antibody concentration of convalescent plasma and time for NAA test turning negative: the convalescent plasma antibody concentration in this study was ranged from 10.93 kAU/L to 114.7 kAU/L, with an average value of (56.44±39.40) kAU/L. NAA test was continuously positive before plasma transfusion in 10 patients, and the time for NAA test turning negative could be counted. Eight patients turned negative from day 2 to day 8 after transfusion. Severe patients showed a shorter time for NAA test turning negative than critical patients after transfusion [2 (2-3) vs. 5 (3-8), P = 0.036]. Two critical patients transfused plasma with lower antibody concentration remained a positive result of NAA test, and died on the 3rd and 6th day respectively. (3) Laboratory results: the change rates of WBC (0.81±0.28 vs. 1.00) and NEU (0.75±0.33 vs. 1.00) were significantly decreased at d1 after convalescent plasma treatment (both P < 0.05), and the CRP level decreased to about 63% of that before transfusion (P = 0.017). No adverse events were observed during convalescent plasma transfusion.
Viral NAA test of most patients with COVID-19 who received convalescent plasma transfusion turned negative from day 2 to day 8 after transfusion, and the turning time of severe patients was shorter than that of critical patients. Convalescent plasma therapy can reduce the patients' CRP level, and no adverse events were found during the treatment. The antibody concentration in the convalescent plasma may be one of the factors that affect the time for the nucleic acid turning negative after transfusion. Detection and screening convalescent plasma of high-titer antibody and early application to severe and critical patients are expected to improve the efficacy of convalescent plasma.
评估恢复期血浆疗法对重症和危重症2019冠状病毒病（COVID-19）患者的有效性和安全性。
从出院2周后的恢复期患者采集200 - 400 mL血浆。经病毒核酸检测和抗体检测后，将血浆输注给16例重症或危重症COVID-19患者。记录病毒核酸扩增（NAA）检测转阴时间、血浆输注总量、平均抗体浓度和总抗体量。检测白细胞（WBC）计数、淋巴细胞（LYM）计数、中性粒细胞（NEU）计数、谷丙转氨酶（ALT）、谷草转氨酶（AST）、C反应蛋白（CRP）、降钙素原（PCT）、乳酸脱氢酶（LDH）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、超敏心肌肌钙蛋白T（hs-cTnT）和乳酸（Lac）水平，并计算输血前基线（d0）、输血后第1天（d1）、第3天（d3）的变化率。
（1）患者特征：16例患者中，5例（31.25%）为重症COVID-19，11例（68.75%）为危重症COVID-19；62.50%（10/16）的患者有基础疾病；危重症患者有创通气和使用体外膜肺氧合（ECMO）的比例分别为90.91%（10/11）和45.46%（5/11）。（2）恢复期血浆抗体浓度及NAA检测转阴时间：本研究中恢复期血浆抗体浓度为10.93 kAU/L至114.7 kAU/L，平均值为（56.44±39.40）kAU/L。10例患者输血前NAA检测持续阳性，可统计NAA检测转阴时间。8例患者输血后第2天至第8天转阴。输血后重症患者NAA检测转阴时间短于危重症患者[2（2 - 3）天对5（3 - 8）天，P = 0.036]。2例输注抗体浓度较低血浆的危重症患者NAA检测仍为阳性结果，分别于第3天和第6天死亡。（3）实验室结果：恢复期血浆治疗后d1时WBC（0.81±0.28对1.00）和NEU（0.75±0.33对1.00）变化率显著降低（均P < 0.05），CRP水平降至输血前的约63%（P = 0.017）。恢复期血浆输注过程中未观察到不良事件。
多数接受恢复期血浆输注的COVID-19患者病毒NAA检测在输血后第2天至第8天转阴，重症患者转阴时间短于危重症患者。恢复期血浆疗法可降低患者CRP水平，治疗过程中未发现不良事件。恢复期血浆中的抗体浓度可能是影响输血后核酸转阴时间的因素之一。检测和筛选高滴度抗体的恢复期血浆并早期应用于重症和危重症患者有望提高恢复期血浆的疗效。
