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Meta-Analysis
. 2022 Jan 4;5(1):e2147331.
doi: 10.1001/jamanetworkopen.2021.47331.

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

Andrea B Troxel  1 , Eva Petkova  1   2   3 , Keith Goldfeld  1 , Mengling Liu  1   4 , Thaddeus Tarpey  1 , Yinxiang Wu  5 , Danni Wu  1 , Anup Agarwal  6 , Cristina Avendaño-Solá  7 , Emma Bainbridge  8 , Katherine J Bar  9 , Timothy Devos  10 , Rafael F Duarte  7 , Arvind Gharbharan  11 , Priscilla Y Hsue  8 , Gunjan Kumar  6 , Annie F Luetkemeyer  8 , Geert Meyfroidt  12 , André M Nicola  13 , Aparna Mukherjee  6 , Mila B Ortigoza  14   15 , Liise-Anne Pirofski  16   17 , Bart J A Rijnders  11 , Casper Rokx  11 , Arantxa Sancho-Lopez  7 , Pamela Shaw  18 , Pablo Tebas  9 , Hyun-Ah Yoon  16   17 , Corita Grudzen  1   19 , Judith Hochman  14 , Elliott M Antman  20
Affiliations
Meta-Analysis

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

Andrea B Troxel et al. JAMA Netw Open. .

Erratum in

  • Error in Figure 3.
    [No authors listed] [No authors listed] JAMA Netw Open. 2022 Mar 1;5(3):e224556. doi: 10.1001/jamanetworkopen.2022.4556. JAMA Netw Open. 2022. PMID: 35244706 Free PMC article. No abstract available.

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Petkova reported receiving grants from the National Institutes of Health outside the submitted work. Dr Devos reported receiving grants from Belgian Health Care Knowledge Centre during the conduct of the study. Dr Duarte reported receiving personal fees from Amgen, Astellas, Bristol Myers Squibb, Gilead Sciences, Jazz Pharmaceuticals, Kiadis Pharma, Miltenyi Biotec, Merck Sharp and Dohme, Omeros, Pfizer, Sanofi-Oncology, Sobi, and Takeda outside the submitted work. Dr Hsue reported receiving honoraria from Gilead and Merck and grants from Novartis outside the submitted work. Dr Luetkemeyer reported receiving grants from Marti and Steve Diamond Charitable Foundation (research grant support to University of California, San Francisco) during the conduct of the study. Dr Meyfroidt reported receiving grants from Belgian Health Care Knowledge Center (Dawn plasma trial funding) and grants from Research Foundation Flanders, Belgium (senior clinical investigator) outside the submitted work. Dr Nicola reported receiving grants from Fundação de Apoio à Pesquisa do Distrito Federal during the conduct of the study. Dr Pirofski reported receiving grants from Mathers Foundation during the conduct of the study. Dr Rijnders reported receiving grants from Erasmus Foundation during the conduct of the study. Dr Rokx reported receiving grants from Viiv, Gilead, and Janssen outside the submitted work. Dr Sancho-Lopez reported receiving personal fees from Bayer, Novartis, Merck, Boehringer Ingelheim, Lilly, GSK, and Incyte outside the submitted work. Dr Yoon reported receiving grants from G. Harold and Leila Y. Mathers Foundation during the conduct of the study. Dr Grudzen reported receiving grants from the National Institute on Aging, National Center for Complementary and Integrative Health, Patient-Centered Outcomes Research Institute, and Samuels Foundation outside the submitted work. Dr Hochman reported receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Proportion of Participants at Different Clinical Stages of COVID-19 Measured on the World Health Organization (WHO) 11-Point Scale at Days 14 and 28 by Treatment Group
CCP indicates COVID-19 convalescent plasma.
Figure 2.
Figure 2.. Change in World Health Organization (WHO) Scores by Treatment
Positive change scores indicate improvement from baseline and are shown in blue; negative change scores indicate worsening and are shown in orange. The abscissa shows the percentage of patients with different changes in scores. Larger blue areas and smaller orange areas in the COVID-19 convalescent plasma (CCP) group compared with control are indicative of CCP association with better outcomes.
Figure 3.
Figure 3.. Posterior Distribution of the Odds Ratios (ORs) From the Cumulative Odds Model for World Health Organization (WHO) Scores and the Binary Outcome of WHO Score 7 or Higher at Day 14 With Adjustment for the Parsimonious Covariate Set
The curves with dashed lines indicate the prior distributions. The stopping rules were probability greater than 0.95 of an OR less than 1 and probability greater than 0.5 of an OR less than 0.8 for both outcomes; these are indicated with vertical dashed lines, respectively. Meta-analysis forest plots show bayesian estimates of the median ORs with their 95% credible intervals (CrIs) for individual randomized clinical trials,,,,,,, and for the pooled OR.
See this image and copyright information in PMC

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