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Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19A Systematic Review and Meta-analysis

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is treatment with convalescent plasma associated with improved clinical outcomes?

Findings  In a meta-analysis of 4 peer-reviewed and published randomized clinical trials including 1060 patients with COVID-19 treated with convalescent plasma vs control, the risk ratio for mortality was 0.93 and after the addition of 6 unpublished randomized clinical trials and 10 722 patients, the risk ratio for mortality was 1.02; neither finding was statistically significant. No significant associations with benefit were shown for hospital length of stay, mechanical ventilation use, clinical improvement, or clinical deterioration.

Meaning  Among patients with COVID-19, treatment with convalescent plasma compared with control was not associated with improved survival or other positive clinical outcomes.


Importance  Convalescent plasma is a proposed treatment for COVID-19.

Objective  To assess clinical outcomes with convalescent plasma treatment vs placebo or standard of care in peer-reviewed and preprint publications or press releases of randomized clinical trials (RCTs).

Data Sources  PubMed, the Cochrane COVID-19 trial registry, and the Living Overview of Evidence platform were searched until January 29, 2021.

Study Selection  The RCTs selected compared any type of convalescent plasma vs placebo or standard of care for patients with confirmed or suspected COVID-19 in any treatment setting.

Data Extraction and Synthesis  Two reviewers independently extracted data on relevant clinical outcomes, trial characteristics, and patient characteristics and used the Cochrane Risk of Bias Assessment Tool. The primary analysis included peer-reviewed publications of RCTs only, whereas the secondary analysis included all publicly available RCT data (peer-reviewed publications, preprints, and press releases). Inverse variance–weighted meta-analyses were conducted to summarize the treatment effects. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation.

Main Outcomes and Measures  All-cause mortality, length of hospital stay, clinical improvement, clinical deterioration, mechanical ventilation use, and serious adverse events.

Results  A total of 1060 patients from 4 peer-reviewed RCTs and 10 722 patients from 6 other publicly available RCTs were included. The summary risk ratio (RR) for all-cause mortality with convalescent plasma in the 4 peer-reviewed RCTs was 0.93 (95% CI, 0.63 to 1.38), the absolute risk difference was −1.21% (95% CI, −5.29% to 2.88%), and there was low certainty of the evidence due to imprecision. Across all 10 RCTs, the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data. Among the peer-reviewed RCTs, the summary hazard ratio was 1.17 (95% CI, 0.07 to 20.34) for length of hospital stay, the summary RR was 0.76 (95% CI, 0.20 to 2.87) for mechanical ventilation use (the absolute risk difference for mechanical ventilation use was −2.56% [95% CI, −13.16% to 8.05%]), and there was low certainty of the evidence due to imprecision for both outcomes. Limited data on clinical improvement, clinical deterioration, and serious adverse events showed no significant differences.

Conclusions and Relevance  Treatment with convalescent plasma compared with placebo or standard of care was not significantly associated with a decrease in all-cause mortality or with any benefit for other clinical outcomes. The certainty of the evidence was low to moderate for all-cause mortality and low for other outcomes.

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Article Information

Corresponding Author: Lars G. Hemkens, MD, MPH, Department of Clinical Research, University Hospital Basel, Spitalstrasse 12, CH-4031 Basel, Switzerland (lars.hemkens@usb.ch).

Accepted for Publication: February 15, 2021.

Published Online: February 26, 2021. doi:10.1001/jama.2021.2747

Author Contributions: Drs Janiaud and Hemkens had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Janiaud and Axfors contributed equally to this study.

Concept and design: Janiaud, Axfors, Smith, Khanna, Moher, Ioannidis, Hemkens.

Acquisition, analysis, or interpretation of data: Janiaud, Axfors, Schmitt, Gloy, Ebrahimi, Hepprich, Haber, Khanna, Moher, Goodman, Ioannidis, Hemkens.

Drafting of the manuscript: Janiaud, Axfors, Hepprich, Hemkens.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Janiaud, Hepprich, Haber, Moher, Ioannidis, Hemkens.

Obtained funding: Hemkens.

Administrative, technical, or material support: Janiaud, Axfors, Gloy, Ebrahimi, Hepprich, Smith.

Supervision: Ioannidis, Hemkens.

Conflict of Interest Disclosures: None reported.

Funding/Support: The Meta-Research Innovation Center at Stanford (Stanford University) is supported by a grant from the Laura and John Arnold Foundation. Dr Axfors is supported by postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr Khanna is supported by the Swiss National Science Foundation and the National Center of Competence in Research. Drs Janiaud and Hemkens are supported by grants from Swiss National Science Foundation.

Role of the Funder/Sponsor: The funders/sponsors 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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