Dataset Information

Convalescent plasma for COVID-19: a meta-analysis, trial sequential analysis, and meta-regression.

ABSTRACT:

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression.

Methods

We performed a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of RCTs to evaluate the benefit of convalescent plasma for COVID-19. The primary outcome was 28-30 day mortality. Secondary outcomes included need for mechanical ventilation and ICU admission. Data sources were PubMed, Embase, MedRxiv, and the Cochrane library on July 2, 2021.

Results

We identified 17 RCTs that recruited 15 587 patients with 8027 (51.5%) allocated to receive convalescent plasma. Convalescent plasma use was not associated with a mortality benefit (24.7% vs 25.5%; odds ratio [OR]=0.94 [0.85-1.04]; P=0.23; I²=4%; TSA adjusted confidence interval [CI], 0.84-1.05), or reduction in need for mechanical ventilation (15.7% vs 15.4%; OR=1.01 [0.92-1.11]; P=0.82; I²=0%; TSA adjusted CI, 0.91-1.13), or ICU admission (22.4% vs 16.7%; OR=0.80 [0.21-3.09]; P=0.75; I²=63%; TSA adjusted CI, 0.0-196.05). Meta-regression did not reveal association with titre of convalescent plasma, timing of administration, or risk of death and treatment effect (P>0.05). Risk of bias was high in most studies.

Conclusions

In patients with COVID-19, there was no clear mortality benefit associated with convalescent plasma treatment. In patients with mild disease, convalescent plasma did not prevent either the need for mechanical ventilation or ICU admission.

Clinical trial registration

CRD42021234201 (PROSPERO).

SUBMITTER: Snow TAC

PROVIDER: S-EPMC8403663 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:Current evidence from randomized controlled trials (RCTs) and systematic reviews on the utility of convalescent plasma (CP) in patients with coronavirus disease 2019 (COVID-19) suggests a lack of benefit. We conducted an updated meta-analysis of RCTs with trial sequential analysis to investigate whether convalescent plasma is futile in reducing mortality in patients hospitalized with COVID-19. We searched 6 databases from December 1, 2019 to August 1, 2021 for RCTs comparing the use of CP with standard of care or transfusion of non-CP standard plasma in patients with COVID-19. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 Tool. Random effects (DerSimonian and Laird) meta-analyses were conducted. The primary outcome was the aggregate risk for in-hospital mortality between both arms. We conducted a trial sequential analysis (TSA) based on the pooled relative risks (RRs) for in-hospital mortality. Secondary outcomes included the pooled RR for receipt of mechanical ventilation and mean difference in hospital length of stay. We included 18 RCTs (8702 CP, 7906 control). CP was not associated with a significant mortality benefit (RR: 0.95, 95%-CI: 0.86-1.04, P = .27, high certainty). Subgroup analysis did not find any significant differences (pinteraction = 0.30) between patients who received CP within 8 days of symptom onset (RR: 0.97, 95%-CI: 0.79-1.19, P = .80), or after 8 days (RR: 0.79, 95%-CI: 0.57-1.10, P = .16). TSA based on a RR reduction of 10% from a baseline mortality of 20% found that CP was not effective, with the pooled effect within the boundary for futility. CP did not significantly reduce the requirement for mechanical ventilation (RR: 1.00, 95%-CI: 0.91-1.10, P = .99, moderate certainty) or hospital length of stay (+1.32, 95%-CI: -1.86 to +4.52, P = .42, low certainty). CP does not improve relevant clinical outcomes in patients with COVID-19, especially in severe disease. The pooled effect of mortality was within the boundary of futility, suggesting the lack of benefit of CP in patients hospitalized with COVID-19.