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

Abstract

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the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data.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

Figure 1.. Risk of Bias Assessments for the Outcomes of All-Cause Mortality, Length of Hospital Stay, and Mechanical Ventilation Use

Three of the trials did not have study acronyms (only trial registration numbers) and ILBS-COVID-02 and PLACID did not have expansions in the original publications. ConCOVID indicates Convalescent Plasma as Therapy for Covid-19 Severe SARS-CoV-2 Disease; ConPlas-19, Convalescent Plasma Therapy vs SOC for the Treatment of COVID-19 in Hospitalized Patients; NA, not available; PICP19, Passive Immunization With Convalescent Plasma in Severe COVID-19 Disease; PlasmAr, Convalescent Plasma and Placebo for the Treatment of COVID-19 Severe Pneumonia; RECOVERY, Randomized Evaluation of COVID-19 Therapy. ^aThere was no detailed information reported regarding (1) the randomization process or (2) the concealment of randomized assignment. ^bThere was no detailed information reported regarding (1) the randomization process, (2) the concealment of randomized assignment, (3) the flow of patients through the trial, and (4) possible deviations from the intended interventions due to the open-label setting of the trial. ^cThe results were communicated as a press release. The assessment of this trial considered the study protocol and publications reporting results from other treatment groups of the trial.^,,,,

Figure 2.. Association of Convalescent Plasma With All-Cause Mortality, Length of Hospital Stay, and Mechanical Ventilation Use in Peer-Reviewed Trials and Non–Peer-Reviewed Trials (Preprints and the RECOVERY Trial)

Three of the trials did not have study acronyms (only trial registration numbers) and ILBS-COVID-02 and PLACID did not have expansions in the original publications. Hartung-Knapp adjustment was used for the random-effects model and the Paule-Mandel estimator was used for τ². The weight percentages correspond to the secondary analysis for all studies. ConCOVID indicates Convalescent Plasma as Therapy for Covid-19 Severe SARS-CoV-2 Disease; ConPlas-19, Convalescent Plasma Therapy vs SOC for the Treatment of COVID-19 in Hospitalized Patients; HR, hazard ratio; NA, not available; PICP19, Passive Immunization With Convalescent Plasma in Severe COVID-19 Disease; PlasmAr, Convalescent Plasma and Placebo for the Treatment of COVID-19 Severe Pneumonia; RECOVERY, Randomized Evaluation of COVID-19 Therapy; RR, risk ratio. ^aIncludes only the studies shown that were published in peer-reviewed journals or as preprints.