Effectiveness of convalescent plasma therapy in severe COVID-19 patients

Kai Duan; Bende Liu; Cesheng Li; Huajun Zhang; Ting Yu; Jieming Qu; Min Zhou; Li Chen; Shengli Meng; Yong Hu; Cheng Peng; Mingchao Yuan; Jinyan Huang; Zejun Wang; Jianhong Yu; Xiaoxiao Gao; Dan Wang; Xiaoqi Yu; Li Li; Jiayou Zhang; Xiao Wu; Bei Li; Yanping Xu; Wei Chen; Yan Peng; Yeqin Hu; Lianzhen Lin; Xuefei Liu; Shihe Huang; Zhijun Zhou; Lianghao Zhang; Yue Wang; Zhi Zhang; Kun Deng; Zhiwu Xia; Qin Gong; Wei Zhang; Xiaobei Zheng; Ying Liu; Huichuan Yang; Dongbo Zhou; Ding Yu; Jifeng Hou; Zhengli Shi; Saijuan Chen; Zhu Chen; Xinxin Zhang; Xiaoming Yang

doi:10.1073/pnas.2004168117

New Research In

Contributed by Zhu Chen, March 18, 2020 (sent for review March 5, 2020; reviewed by W. Ian Lipkin and Fusheng Wang)

This article has Letters. Please see:

Convalescent plasma for patients with COVID-19 - May 12, 2020
Get rid of the bad first: Therapeutic plasma exchange with convalescent plasma for severe COVID-19 - May 12, 2020

See related content:

Reply to Kesici et al. and Zeng et al.: Blocking the virus and reducing the inflammatory damage in COVID-19
- May 12, 2020

Significance

COVID-19 is currently a big threat to global health. However, no specific antiviral agents are available for its treatment. In this work, we explore the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was well tolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 d. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 d. Radiological examination showed varying degrees of absorption of lung lesions within 7 d. These results indicate that CP can serve as a promising rescue option for severe COVID-19, while the randomized trial is warranted.

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 × 10⁹/L vs. 0.76 × 10⁹/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.

Footnotes

↵¹K. Duan, B. Liu, C.L., H.Z., T.Y., J.Q., M.Z., and L.C. contributed equally to this work.
↵²To whom correspondence may be addressed. Email: zchen{at}stn.sh.cn, zhangx{at}shsmu.edu.cn, or yangxiaoming{at}sinopharm.com.

Author contributions: Z.C., X. Zhang, and X. Yang designed research; S.M., Yong Hu, C.P., M.Y., Z.W., J.Y., X.G., D.W., L. Li, J.Z., X.W., B. Li, W.C., Y.P., Yeqin Hu, L. Lin, S.H., Z. Zhou, L.Z., Y.W., Z. Zhang, K. Deng, Z.X., Q.G., W.Z., X. Zheng, Y.L., H.Y., D.Z., D.Y., J. Hou, and Z.S. performed research; J. Huang, X. Yu, Y.X., X.L., S.C., and Z.C. analyzed data; and K. Duan, B. Liu, C.L., H.Z., T.Y., J.Q., M.Z., L.C., and Z.C. wrote the paper.
Reviewers: W.I.L., Columbia University; and F.W., Beijing 302 Hospital.
The authors declare no competing interest.
Data deposition: Detailed data on patients that support the findings of this study have been deposited in the Open Science Framework (https://osf.io/gahz5).
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2004168117/-/DCSupplemental.

This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

View Full Text