Effectiveness of convalescent plasma therapy in severe COVID-19 patients

  1. Kai Duan
  2. Bende Liu
  3. Cesheng Li
  4. Huajun Zhang
  5. Ting Yu
  6. Jieming Qu
  7. Min Zhou
  8. Li Chen
  9. Shengli Meng
  10. Yong Hu
  11. Cheng Peng
  12. Mingchao Yuan
  13. Jinyan Huang
  14. Zejun Wang
  15. Jianhong Yu
  16. Xiaoxiao Gao
  17. Dan Wang
  18. Xiaoqi Yu
  19. Li Li
  20. Jiayou Zhang
  21. Xiao Wu
  22. Bei Li
  23. Yanping Xu
  24. Wei Chen
  25. Yan Peng
  26. Yeqin Hu
  27. Lianzhen Lin
  28. Xuefei Liu
  29. Shihe Huang
  30. Zhijun Zhou
  31. Lianghao Zhang
  32. Yue Wang
  33. Zhi Zhang
  34. Kun Deng
  35. Zhiwu Xia
  36. Qin Gong
  37. Wei Zhang
  38. Xiaobei Zheng
  39. Ying Liu
  40. Huichuan Yang
  41. Dongbo Zhou
  42. Ding Yu
  43. Jifeng Hou
  44. Zhengli Shi
  45. Saijuan Chen
  46. Zhu Chen
  47. Xinxin Zhang
  48. Xiaoming Yang

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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 9 /L vs. 0.76 × 10 9 /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.

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  1. ScreenIT

    SciScore for 10.1101/2020.03.16.20036145: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Cases with serious general conditions, such as severe organ dysfunction, who were not suitable for CP transfusion; Written informed consent according to the Declaration of Helsinki was obtained from each patient or legal relatives.
    IRB: This study was approved by the Ethics Committee of the China National Biotec Group Co., Ltd. (Approval number:2020-0001).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Graphs were plotted using GraphPad Prism 7.0.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical software used included SPSS 24.0.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There were some limitations to the present study. First, except for CP transfusion, the patients received other standard cares. All patients received antiviral treatment despite the uncertainty of the efficacy of drugs used. As a result, the possibility thatthese antiviral agents could contribute to the recovery of patients, or synergize with the therapeutic effect of CP, could not be ruled out. Furthermore, some patients received glucocorticoid therapy, which might interfere with immune response and delay virus clearance. Second, the median time from onset of symptoms to CP transfusion was 16.5 days (IQR11.0-19.3 days). Although the kinetics of viremia during natural history remains unclear, the relationship between SARS-CoV-2 RNA reduction and CP therapy, as well asthe optimal concentration of neutralizing antibodies and treatment schedule, should be further clarified. Third, the dynamic changes of cytokines during treatment were not investigated. Nevertheless, the preliminary results of this trial seem promising, justifying a randomized controlled clinical trial in a larger patient cohort. In conclusion, this pilot study on CP therapy showed a potential therapeutic effect and low risk in the treatment of severe COVID-19 patients. One dose of CP with high concentration of neutralizing antibodies can rapidly reduce the viral load and tends to improve clinical outcomes. The optimal dose and treatment time point, as well as the definite clinical benefits of CP therapy, need to...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1073/pnas.2004168117
  3. Version published to 10.1101/2020.03.16.20036145v1 on medRxiv