Convalescent Plasma in the Treatment of Severe COVID-19: A Systematic Review and Meta-Analysis

Zhang, Xuanguo; Li, Xi; Pang, Fang; Du, Yan; Yuan, Qiuzhen; Shi, Minjuan; Liu, Jiping; Ma, Hui; Li, Bo

doi:10.18502/ijph.v49i11.4716

Cited by 7 publications

(13 citation statements)

References 21 publications

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“…We identified almost a hundred eligible trials that evaluate evidence on convalescent plasma treatment in patients with COVID-19. Among 21 other systematic reviews and meta-analyses on this topic that were available on PubMed as of mid-April, 2021 [ 5 , 46 , 47 , 51 – 68 ], 15 include only 0 to 2 randomized trials alongside observational studies (e.g., two LSR) [ 46 , 47 , 51 – 63 ] and the two most comprehensive reviews included 10 RCTs [ 5 , 64 ]. One of the latter meta-analyses [ 5 ] does not include the RECOVERY Trial and includes one trial that we categorized as non-randomized [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

et al. 2021

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Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

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Section: Discussionmentioning

confidence: 99%

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

et al. 2021

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“…The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram is reported in Figure 1 . After the full texts were scrutinized against the inclusion and exclusion criteria, 29 SRs were included in the umbrella review [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ] and 23 SRs were excluded [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , …”

Section: Resultsmentioning

confidence: 99%

“…Of the 29 SRs included in the overview, 26 were focused exclusively on COVID-19 [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], while three were focused on respiratory pandemics and on beta coronaviruses infections [ 10 , 19 , 30 ]. Two SRs [ 17 , 22 ] were a subgroup analysis of other reviews [ 16 , 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…Twenty-eight SRs were focused on CP treatment of COVID-19, while one study [ 25 ] was focused on both CP prophylaxis and treatment. The majority of the SRs analyzed COVID-19 at any stage of disease severity, while four studies [ 10 , 30 , 36 , 38 ] were focused on more advanced (severe and/or critical) stages. Most SRs analyzed COVID-19 patients with no limitation of age, gender or ethnicity, while four SRs were focused only on adult (>18 years) COVID-19 patients [ 11 , 20 , 31 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

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Safety and Efficacy of Convalescent Plasma in COVID-19: An Overview of Systematic Reviews

Franchini

Corsini²,

Focosi³

et al. 2021

Diagnostics

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Convalescent plasma (CP) from patients recovered from COVID-19 is one of the most studied anti-viral therapies against SARS-COV-2 infection. The aim of this study is to summarize the evidence from the available systematic reviews on the efficacy and safety of CP in COVID-19 through an overview of the published systematic reviews (SRs). A systematic literature search was conducted up to August 2021 in Embase, PubMed, Web of Science, Cochrane and Medrxiv databases to identify systematic reviews focusing on CP use in COVID-19. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. The following outcomes were analyzed: mortality, viral clearance, clinical improvement, length of hospital stay, adverse reactions. In addition, where possible, subgroup analyses were performed according to study design (e.g., RCTs vs. non-RCTs), CP neutralizing antibody titer and timing of administration, and disease severity. The methodological quality of included studies was assessed using the checklist for systematic reviews AMSTAR-2 and the GRADE assessment. Overall, 29 SRs met the inclusion criteria based on 53 unique primary studies (17 RCT and 36 non-RCT). Limitations to the methodological quality of reviews most commonly related to absence of a protocol (11/29) and funding sources of primary studies (27/29). Of the 89 analyses on which GRADE judgements were made, effect estimates were judged to be of high/moderate certainty in four analyses, moderate in 38, low in 38, very low in nine. Despite the variability in the certainty of the evidence, mostly related to the risk of bias and inconsistency, the results of this umbrella review highlight a mortality reduction in CP over standard therapy when administered early and at high titer, without increased adverse reactions.

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“…It was found that convalescent plasma did not improve clinical symptoms but reduced the risk of death in patients with severe infections [7]. A meta-analysis by Zhang and Sun et al incorporating observational and retrospective studies came to a similar conclusion that convalescent plasma reduces the risk of death in patients with severe infections [26,27]. However, recent RCT studies have found that convalescent plasma did not improve the prognosis of patients with severe disease [9,[14][15][16][17].…”

Section: Discussionmentioning

confidence: 99%

Convalescent Plasma Therapy in Severe and Critically Ill COVID-19 Patients: A Systematic Review and Meta-Analysis

Pan

Wang

Zheng

et al. 2021

Preprint

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Background: Convalescent plasma treatment of severe and critically ill Corona Virus Disease 2019(COVID-19) patients is still controversial.Objective: To evaluate the efficacy and safety of convalescent plasma in patients with severe COVID-19 infection and critically ill patients, We performed a meta-analysis and systematic review of convalescent plasma therapy in severe and critically ill COVID-19 patients.Methods: We conducted a literature search in electronic data and citations of previously published systematic reviews. We included only randomized controlled studies on convalescent plasma for the treatment of severe and critically ill COVID-19 patients. Results: A total of 7 randomized controlled trials and 1363 patients were included in the meta-analysis. Compared to patients of the control group, there was no difference in clinical improvement (Four studies, RR 1.06, 95% CI 0.96 to 1.17, p = 0.22, moderate certainty) and mortality (seven studies, RR 0.86, 95% CI 0.66 to 1.11, p = 0.48, moderate certainty) for patients of convalescent plasma therapy group.Conclusion: Convalescent plasma does not reduce the improvement of symptoms and the risk of death in severely infected and critically ill COVID-19 patients

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Convalescent Plasma in the Treatment of Severe COVID-19: A Systematic Review and Meta-Analysis

Cited by 7 publications

References 21 publications

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Safety and Efficacy of Convalescent Plasma in COVID-19: An Overview of Systematic Reviews

Convalescent Plasma Therapy in Severe and Critically Ill COVID-19 Patients: A Systematic Review and Meta-Analysis

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