Efficacy and Safety of Convalescent Plasma for COVID-19: A Systematic Review and Meta-analysis

Abstract

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 Information The online version contains supplementary material available at 10.1007/s12288-021-01417-w.

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

“…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 , …”

“…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 ].…”

SARS-CoV-2 antibody changes in patients receiving COVID-19 convalescent plasma from normal and vaccinated donors

“…Multiple reports describe the rationale for this therapy and several studies provide some evidence of efficacy [ [5] , [6] , [7] , [8] , [9] , [10] ]. However, other trials have failed to show the benefit of CCP in hospitalized patients [ 11 ] and meta-analyses to date have drawn equivocal conclusions about the efficacy of CCP [ [12] , [13] , [14] ]. The closing of both the REMAP-CAP trial (NCT02735707) and the RECOVERY trial (NCT04381936), halted due to futility, have dampened enthusiasm for CCP.…”

SARS-CoV-2 antibody changes in patients receiving COVID-19 convalescent plasma from normal and vaccinated donors

“…Multiple reports describe the rationale for this therapy and several studies provide some evidence of efficacy [5][6][7][8][9][10]. However, other trials have failed to show the benefit of CCP in hospitalized patients [11] and meta-analyses to date have drawn equivocal conclusions about the efficacy of CCP [12][13][14]. The closing of both the REMAP-CAP trial (NCT02735707) and the RECOVERY trial (NCT04381936), halted due to futility, have greatly dampened enthusiasm for CCP, however, it continues to be used for select patient populations.…”