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Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma

Educational Objective
To understand if administration of convalescent plasma transfusion is beneficial in the treatment of critically ill patients with COVID-19
1 Credit CME
Key Points

Question  Could administration of convalescent plasma transfusion be beneficial in the treatment of critically ill patients with coronavirus disease 2019 (COVID-19)?

Findings  In this uncontrolled case series of 5 critically ill patients with COVID-19 and acute respiratory distress syndrome (ARDS), administration of convalescent plasma containing neutralizing antibody was followed by an improvement in clinical status.

Meaning  These preliminary findings raise the possibility that convalescent plasma transfusion may be helpful in the treatment of critically ill patients with COVID-19 and ARDS, but this approach requires evaluation in randomized clinical trials.

Abstract

Importance  Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments.

Objective  To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Design, Setting, and Participants  Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; Pao2/Fio2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion.

Exposures  Patients received transfusion with convalescent plasma with a SARS-CoV-2–specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission.

Main Outcomes and Measures  Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), Pao2/Fio2, viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion.

Results  All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and Pao2/Fio2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2–specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion.

Conclusions and Relevance  In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.

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Article Information

Corresponding Authors: Yingxia Liu, MD (yingxialiu@hotmail.com), Zheng Zhang, MD (zhangzheng1975@aliyun.com), and Lei Liu, MD (liulei3322@aliyun.com), Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, No. 29, Bulan Road, Longgang District, Shenzhen 518112, China.

Accepted for Publication: March 20, 2020.

Published Online: March 27, 2020. doi:10.1001/jama.2020.4783

Author Contributions: Dr L. Liu had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Shen, Z. Wang, Zhao, and Y. Yang contributed equally.

Concept and design: Shen, Z. Wang, Yuan, F. Wang, D. Liu, Zhang, Y. Liu, L. Liu.
Acquisition, analysis, or interpretation of data: Shen, Yang Yang, J. Li, Yuan, D. Li, M. Yang, Xing, Wei, Xiao, Yan Yang, Qu, Qing, L. Chen, Xu, Peng, Y. Li, Zheng, F. Chen, Huang, Jiang, Y. Liu, L. Liu.
Drafting of the manuscript: Shen, Zhao, Yang Yang, J. Li, Yuan, F. Wang, M. Yang, Xing, Wei, Xiao, Yan Yang, Qu, Qing, L. Chen, Xu, Zheng, Huang, Jiang, D. Liu, Y. Liu, L. Liu.
Critical revision of the manuscript for important intellectual content: Shen, Z. Wang, Yang Yang, Yuan, D. Li, Peng, Y. Li, F. Chen, Zhang, Y. Liu, L. Liu.
Statistical analysis: Yuan.
Obtained funding: Yuan, Zhang, Y. Liu, L. Liu.
Administrative, technical, or material support: Shen, Zhao, J. Li, Yuan, F. Wang, D. Li, M. Yang, Yan Yang, Qu, Qing, L. Chen, Zhang.
Supervision: Z. Wang, Yuan, Zhang, Y. Liu, L. Liu.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by the National Science and Technology Major Project (2018ZX10711001, 2017ZX10103011, 2017ZX10204401), Sanming Project of Medicine in Shenzhen (SZSM201412003, SZSM201512005), China Postdoctoral Science Foundation (2019T120147, 2018M641508), Shenzhen Science and Technology Research and Development Project (202002073000001), National Natural Science Foundation of China (81902058), Shenzhen Science and Technology Research and Development Project (202002073000002), and The Key Technology R&D Program of Tianjin (17YFZCSY01090).

Role of the Funder/Sponsor: The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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