COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

COVID-19 Evidence Alerts needs your support. If our service is of value to you, please consider donating to keep it going. Learn more Donate now

Treatment Janiaud P, Axfors C, Schmitt AM, et al. Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis. JAMA. 2021 Mar 23;325(12):1185-1195. doi: 10.1001/jama.2021.2747.

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the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data.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.

Discipline / Specialty Area Score
Infectious Disease
Intensivist/Critical Care
Hospital Doctor/Hospitalists
Internal Medicine
Comments from MORE raters

Infectious Disease rater

This is a very important and updated systematic review in a critical topic. Some concerns: 1. RECOVERY, the bigger trial about plasma, is not still published. 2. Not all the trials used plasma with really high titers of neutralizing antibodies. 3. Patients outside of ICU and without mechanical ventilation, but at risk of it, may benefit of this intervention.

Internal Medicine rater

Several trials of convalescent plasma for Covid-19 have recently been halted for futility. This review and meta-analysis sums up the available evidence; there is no clinical benefit.

Respirology/Pulmonology rater

The attempt at meta-analysis of studies using convalescent plasma to treat Covid-19 infections suggests lack of any benefit. The quality of the data was not optimal, and further studies are in process. It remains unclear if there is a subset of Covid-19 patients that might benefit from this therapy.