Association of Convalescent Plasma Treatment With Clinical Status in Patients Hospitalized With COVID-19 : A Meta-analysis

Key Points

Question

What is the pooled evidence from high-quality randomized clinical trials regarding the safety and potential benefit of convalescent plasma to treat hospitalized patients with COVID-19?

Findings

In this meta-analysis of 8 randomized clinical trials enrolling 2341 participants, individual patient data were monitored in real time and analyzed using a robust bayesian framework and advanced statistical modeling. No association of convalescent plasma with clinical outcomes was found.

Meaning

These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.

Abstract

This meta-analysis examines individual patient data from 8 randomized clinical trials of COVID-19 convalescent plasma to determine its safety and efficacy in treating hospitalized patients with COVID-19.

Abstract

Importance

COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing.

Objective

To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP.

Data Sources

From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly.

Study Selection

Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally.

Data Extraction and Synthesis

A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board.

Main Outcomes and Measures

Prespecified coprimary end points—the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model—were assessed clinically at 14 days after randomization.

Results

Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics.

Conclusions and Relevance

This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.