Dataset Information

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the summary RR was 1.02 (95% CI, 0.92 to 1.12) and there was moderate certainty of the evidence due to inclusion of unpublished data.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

SUBMITTER: Janiaud P

PROVIDER: S-EPMC7911095 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundConvalescent 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 ).MethodsIn 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.ResultsA 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.ConclusionsConvalescent 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.

Project description:Convalescent plasma is a suggested treatment for Coronavirus disease 2019 (Covid-19), but its efficacy is uncertain. We aimed to evaluate whether the use of convalescent plasma is associated with improved clinical outcomes in patients with Covid-19.In this systematic review and meta-analysis, we searched randomized controlled trials investigating the use of convalescent plasma in patients with Covid-19 in Medline, Embase, Web of Science, Cochrane Library, and medRxiv from inception to October 17th, 2021. Two reviewers independently extracted the data. The primary efficacy outcome was all-cause mortality. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. This study was registered with PROSPERO, CRD42021284861. Of the 8874 studies identified in the initial search, sixteen trials comprising 16 317 patients with Covid-19 were included. In the overall population, the all-cause mortality was 23.8% (2025 of 8524) with convalescent plasma and 24.4% (1903 of 7769) with standard of care (risk ratio (RR) 0.97, 95% CI 0.90-1.04) (high-certainty evidence). All-cause mortality did not differ in the subgroups of noncritically ill (21.7% [1288 of 5929] vs. 22.4% [1320 of 5882]) and critically ill (36.9% [518 of 1404] vs. 36.4% [455 of 1247]) patients with Covid-19. The use of convalescent plasma in patients who tested negative for anti-SARS-CoV-2 antibodies at baseline was not associated with significantly improved survival (RR 0.94, 95% CI 0.87-1.02). In the overall study population, initiation of mechanical ventilation (RR 0.97, 95% CI 0.88-1.07), time to clinical improvement (HR 1.09, 95% CI 0.91-1.30), and time to discharge (HR 0.95, 95% CI 0.89-1.02) were similar between the two groups. In patients with Covid-19, treatment with convalescent plasma, as compared with control, was not associated with lower all-cause mortality or improved disease progression, irrespective of disease severity and baseline antibody status.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021284861).

Project description:IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has spread globally. Therapeutic options including antivirals, anti-inflammatory compounds, and vaccines are still under study. Convalescent plasma(CP) immunotherapy was an effective method for fighting against similar viral infections such as SARS-CoV, and MERS-CoV. In the epidemic of COVID-19, a large number of literatures reported the application of CP. However, there is controversy over the efficacy of CP therapy for COVID-19. This systematic review was designed to evaluate the existing evidence and experience related to CP immunotherapy for COVID-19.MethodsA literature search was conducted on Pubmed, Cochrane Library, Clinical Key, Wanfang Database; China National Knowledge Infrastructure(CNKI) were used to search for the proper keywords such as SARS-CoV-2, COVID-19, plasma, serum, immunoglobulins, blood transfusion, convalescent, novel coronavirus, immune and the related words for publications published until 15.10.2020. Other available resources were also used to identify relevant articles. The present systematic review was performed based on PRISMA protocol. Data extraction and risk of bias assessments were performed by two reviewers.ResultsBased on the inclusions and exclusions criteria, 45 articles were included in the final review. First, meta-analysis results of RCTs showed that, there were no statistically significant differences between CP transfusion and the control group in terms of reducing mortality(OR 0.79, 95% CI 0.52-1.19, I2 = 28%) and improving clinical symptoms(OR 1.21, 95%CI 0.68-2.16; I2 = 0%). The results of controlled NRSIs showed that CP therapy may reduce mortality in COVID-19 patients(RR 0.59, 95% CI 0.53-0.66, I2 = 0%). Second, limited safety data suggested that CP is a well-tolerated therapy with a low incidence of adverse events. But, due to lack of safety data for the control group, it is really not easy to determine whether CP transfusion has an impact on moderate to serious AEs. Thirdly, for children, pregnant, elderly, tumor and immunocompromised patients, CP may be a well-tolerated therapy, if the disease cannot be controlled and continues to progress. Studies were commonly of low or very low quality.ConclusionsAlthough the results of limited RCTs showed that CP cannot significantly reduce mortality, some non-RCTs and case report(series) have found that CP may help patients improve clinical symptoms, clear the virus, and reduce mortality, especially for patients with COVID-19 within ten days of illness. We speculate that CP may be a possible treatment option. High-quality studies are needed for establishing stronger quality of evidence and pharmacists should also be actively involved in the CP treatment process and provide close pharmaceutical care.