The Effect of Convalescent Plasma Therapy on Mortality Among Patients With COVID-19: Systematic Review and Meta-analysis.
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ABSTRACT:
SUBMITTER: Klassen SA
PROVIDER: S-EPMC7888247 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
Publications
The Effect of Convalescent Plasma Therapy on Mortality Among Patients With COVID-19: Systematic Review and Meta-analysis.
Klassen Stephen A SA Senefeld Jonathon W JW Johnson Patrick W PW Carter Rickey E RE Wiggins Chad C CC Shoham Shmuel S Grossman Brenda J BJ Henderson Jeffrey P JP Musser James J Salazar Eric E Hartman William R WR Bouvier Nicole M NM Liu Sean T H STH Pirofski Liise-Anne LA Baker Sarah E SE van Helmond Noud N Wright R Scott RS Fairweather DeLisa D Bruno Katelyn A KA Wang Zhen Z Paneth Nigel S NS Casadevall Arturo A Joyner Michael J MJ
Mayo Clinic proceedings 20210217 5
To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials, 20 matched control studies, 2 dose-response studies, and 96 case reports or case series. Studies published between January 1, 2020, and January 16, 2021, were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of randomized clinical trials and matched control data demonstrated that patients with COVID-19 t ...[more]
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Project description:The purpose of this systematic review and meta-analysis was to examine clinical outcomes associated with convalescent plasma therapy in COVID-19 patients. We performed a literature search on PubMed, medRxiv, Web of Science, and Scopus to identify studies published up to December 10th, 2020 that examined the efficacy of convalescent plasma treatment for COVID-19. The primary endpoints were mortality, clinical improvement, and hospital length of stay. We screened 859 studies that met the search criteria, performed full-text reviews of 56 articles, and identified 15 articles that fulfilled inclusion criteria for meta-analysis. The odds of mortality were significantly lower in the convalescent plasma group compared to the control group (OR = 0.59 [95% CI = 0.44; 0.78], P < .001), although results from two key randomized controlled trials did not support the mortality benefit. The odds of clinical improvement were significantly higher in the convalescent plasma group compared to the control group (OR = 2.02 [95% CI = 1.54; 2.65], P < .001). There was no difference in hospital length of stay between the convalescent plasma group and the control group (MD = -0.49 days [95% CI = -3.11; 2.12], P = .713). In all, these data indicate that a mortality benefit with convalescent plasma is unclear, although there remain benefits with convalescent plasma therapy for COVID-19.
| S-EPMC8014691 | biostudies-literature
Project description:Insight into the clinical potential of convalescent plasma in patients with coronavirus disease (COVID-19) is important given the severe clinical courses in unvaccinated and seronegative individuals. The aim of the study was to investigate whether there is a survival benefit of convalescent plasma therapy in COVID-19 patients. The authors independently assessed randomized controlled trials (RCTs) identified by the search strategy for inclusion, extracted data, and assessed risk of bias. The binary primary outcome was all-cause mortality. Risk ratio (RR) of the convalescent plasma treatment (vs. best standard care) and its associated standard error (effect size) were calculated. A random-effects model was employed to statistically pool the effect sizes of the selected studies. We included 19 RCTs with 17,021 patients. The random-effects model resulted in an estimated pooled RR of 0.94 (95% CI 0.81-1.08, p = 0.33), showing no statistical evidence of the benefit of convalescent plasma therapy on all-cause mortality. Convalescent plasma therapy was not found to be effective in reducing all-cause mortality in COVID-19 patients. Further studies are needed to determine in which patients convalescent plasma therapy may lead to a reduction in mortality.
| S-EPMC10412555 | biostudies-literature
Project description:Abstract Background: While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess the role of convalescent plasma treatment on the clinical outcomes of COVID-19 patients enrolled in randomized controlled trials (RCTs). Methods: A systematic search was conducted in the PubMed database (end-of-search: 29 December 2022) for RCTs on convalescent plasma therapy compared to supportive care\standard of care. Pooled relative risk (RR) and 95% confidence intervals were calculated with random-effects models. Subgroup and meta-regression analyses were also performed, in order to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 34 studies were included in the meta-analysis. Per overall analysis, convalescent plasma treatment was not associated with lower 28-day mortality [RR = 0.98, 95% CI (0.91, 1.06)] or improved 28-day secondary outcomes, such as hospital discharge [RR = 1.00, 95% CI (0.97, 1.03)], ICU-related or score-related outcomes, with effect estimates of RR = 1.00, 95% CI (0.98, 1.05) and RR = 1.06, 95% CI (0.95, 1.17), respectively. However, COVID-19 outpatients treated with convalescent plasma had a 26% less risk of requiring hospital care, when compared to those treated with the standard of care [RR = 0.74, 95% CI (0.56, 0.99)]. Regarding subgroup analyses, COVID-19 patients treated with convalescent plasma had an 8% lower risk of ICU-related disease progression when compared to those treated with the standard of care (with or without placebo or standard plasma infusions) [RR = 0.92, 95% CI (0.85, 0.99)] based on reported outcomes from RCTs carried out in Europe. Finally, convalescent plasma treatment was not associated with improved survival or clinical outcomes in the 14-day subgroup analyses. Conclusions: Outpatients with COVID-19 treated with convalescent plasma had a statistically significantly lower risk of requiring hospital care when compared to those treated with placebo or the standard of care. However, convalescent plasma treatment was not statistically associated with prolonged survival or improved clinical outcomes when compared to placebo or the standard of care, per overall analysis in hospitalized populations. This hints at potential benefits, when used early, to prevent progression to severe disease. Finally, convalescent plasma was significantly associated with better ICU-related outcomes in trials carried out in Europe. Well-designed prospective studies could clarify its potential benefit for specific subpopulations in the post-pandemic era.
| S-EPMC10054551 | biostudies-literature
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).
| S-EPMC8859444 | biostudies-literature
Project description:BackgroundAmong all patients infected with coronavirus disease 2019 (COVID-19), the older adult population was the most affected, with 80%-90% of fatalities occurring in this group. The effectiveness of convalescent plasma (CP) in older adults is considerably more restricted than that in adults, resulting in a demand for data on the efficacy of therapeutic CP in older adults. This meta-analysis of updated literature examined the effect of CP in older adults with COVID-19.MethodsRelevant literature was identified from studies indexed in the Cochrane, PubMed, and Google Scholar databases between December 2019 and April 2022. The primary outcome was all-cause mortality. Risk estimates were pooled using a random-effects model. The risk of bias was assessed by regression-based Egger test using the relative risk (RR) and upper and lower confidence intervals (CIs) of the three included studies.ResultsAmong 377 studies identified, three full-text studies that included 1,038 patients met the inclusion criteria. The results of our meta-analysis showed that CP administration lowered the mortality risk in older adults with COVID-19 (RR=0.47; 95% CI, 0.26-0.86; p=0.01; I2=0%, p<0.81). CP therapy was more useful if delivered early in the course of the disease (within 72 hours of onset) and in less severe stages of the disease. Mortality tended to be lower in the high-titer group.ConclusionsCP treatment was significantly associated with a lower risk of mortality in older adults with COVID-19 than in patients not administered CP. The timing of CP administration is critical since earlier treatment after disease onset was associated with a better prognosis.
| S-EPMC9535370 | biostudies-literature
Project description:Several options to treat hospitalized severe COVID-19 patients have been suggested. The study aimed to describe survival in patients treated with convalescent COVID plasma (CCP) and to identify in-hospital mortality predictors. This prospective cohort study examined data from 112 severe COVID-19 patients hospitalized in the Corona Departments in an acute care hospital who received two units of CCP (at least one of them high-titer). Demographic and medical data was retrieved from the patients' electronic health records (EHR). Possible predictors for in-hospital mortality were analyzed in a univariate analysis and those found to be clinically significant were further analyzed in a multivariable analysis. Median age was 67 years (IQR 55-74) and 66 (58.9%) of them were males. Of them, 20 (17.9%) died in hospital. On multivariable analysis diabetes mellitus (p = 0.004, OR 91.54), mechanical ventilation (p = 0.001, OR 59.07) and lower albumin levels at treatment (p = 0.027, OR 0.74) were significantly associated with increased in-hospital mortality. In our study, in-hospital mortality in patients receiving CCP is similar to that reported for the general population, however certain variables mentioned above were associated with increased in-hospital mortality. In the literature, these variables were also associated with a worse outcome in patients with COVID-19 who did not receive CCP. As evidence points toward a benefit from CCP treatment in immunocompromised patients, we believe the above risk factors can further define COVID-19 patients at increased risk for mortality, enabling the selection of candidates for early treatment in an outpatient setting if possible.
| S-EPMC9295964 | biostudies-literature
Project description:BackgroundConvalescent plasma, widely utilized in viral infections that induce neutralizing antibodies, has been proposed for COVID-19, and preliminary evidence shows that it might have beneficial effect. Our objective was to determine the risk factors for 28-days mortality in patients who received convalescent plasma for COVID-19 compared to those who did not, who were admitted to hospitals in Buenos Aires Province, Argentina, throughout the pandemic.MethodsThis is a multicenter, retrospective cohort study of 2-month duration beginning on June 1, 2020, including unselected, consecutive adult patients with diagnosed COVID-19, admitted to 215 hospitals with pneumonia. Epidemiological and clinical variables were registered in the Provincial Hospital Bed Management System. Convalescent plasma was supplied as part of a centralized, expanded access program.ResultsWe analyzed 3,529 patients with pneumonia, predominantly male, aged 62±17, with arterial hypertension and diabetes as main comorbidities; 51.4% were admitted to the ward, 27.1% to the Intensive Care Unit (ICU), and 21.7% to the ICU with mechanical ventilation requirement (ICU-MV). 28-day mortality was 34.9%; and was 26.3%, 30.1% and 61.4% for ward, ICU and ICU-MV patients. Convalescent plasma was administered to 868 patients (24.6%); their 28-day mortality was significantly lower (25.5% vs. 38.0%, p<0.001). No major adverse effects occurred. Logistic regression analysis identified age, ICU admission with and without MV requirement, diabetes, and preexistent cardiovascular disease as independent predictors of 28-day mortality, whereas convalescent plasma administration acted as a protective factor.ConclusionsOur study suggests that the administration of convalescent plasma in COVID-19 pneumonia admitted to the hospital might be associated with improved outcomes.
| S-EPMC8084206 | biostudies-literature
Project description:Convalescent plasma is currently being used in the treatment of COVID-19. Recommendations regarding use convalescent plasma in COVID-19 requires systematic summaries of available evidence. We searched the databases Medline, Embase, Cochrane CENTRAL, Epistomonikos, Medrxiv and Biorxiv. Title/abstract screening, full text screening and data abstraction were carried out in duplicate by two reviewers. Pooled effect sizes and 95% confidence intervals were calculated using random effects meta-analysis. GRADE tool was used to rate the certainty of evidence. Twenty two studies were found eligible for inclusion: nine randomized controlled trials and thirteen cohort studies. Low certainty evidence from eight RCTs showed inconclusive effects of convalescent plasma on mortality at 28 days (OR 0.85, 95% CI 0.61 to 1.18). Low certainty evidence from thirteen cohort studies showed a reduction in mortality at 28 days (OR 0.66, 95% CI 0.53 to 0.82). The pooled OR for clinical improvement was 1.07 (95% CI 0.86 to 1.34) representing low certainty evidence. Evidence from three RCTs showed inconclusive effect of CP on the need for mechanical ventilation (OR 1.20, 95% CI 0.72 to 1.98). Four cohort studies reporting unadjusted estimates suggested a reduction in the need for mechanical ventilation with convalescent plasma (OR 0.80 95% CI 0.71 to 0.91, low certainty). Pooled estimates from 2 RCTs showed inconclusive effects of convalescent plasma on the proportion of patients with nondetectable levels of virus in nasopharyngeal specimens on day 3 (OR 3.62, 95% CI 0.43, 30.49, very low-quality evidence). The present review reports uncertain estimates on the efficacy of convalescent plasma in the treatment of COVID-19. There is low certainty evidence of a possible reduction in mortality and mechanical ventilation, a faster viral clearance and the absence of any serious adverse events. However, its efficacy for these outcomes requires evidence from good quality and adequately powered randomized controlled trials.Supplementary informationThe online version contains supplementary material available at 10.1007/s12288-021-01417-w.
| S-EPMC7961318 | biostudies-literature
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.
| S-EPMC8605464 | biostudies-literature
Project description: Not available
| S-EPMC9891348 | biostudies-literature