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

Abstract

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.

Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience

“…The results from randomized and non-randomized controlled trials (RCTs) on CCP have produced mixed results, probably due to the wide heterogeneity in their study designs and patient populations enrolled [ 7 ]. Furthermore, these trials were heterogeneous with respect to the characteristics of the CCP used (e.g., in terms of antibody content and stratification of recipients according to their serological status or disease severity).…”

COVID-19 convalescent plasma and randomized clinical trials: explaining conflicting outcomes and finding signals of efficacy

“…Another metanalysis of 18 peer-review clinical trials, 3 preprints, and 26 observational studies actually found that CCP use was associated with reduced risk of all-cause mortality in severe or critical COVID-19 patients (86). A recent umbrella review of 29 metanalyses and systematic reviews found evidences for improvement in the CCP arms for some outcomes (overall mortality, viral clearance at day 3,) but not for others (clinical improvement, length of hospital stay (87).…”

Is Better Standardization of Therapeutic Antibody Quality in Emerging Diseases Epidemics Possible?

“…In addition, evidence is growing (including our work) that the quantity of SARS-CoV-2 specific antibodies is correlated with the severity of disease, highest in the most severe cases ( 32 ), implying that a small additional infusion cannot provide significant benefit. However, there are trials reporting beneficial outcomes of CCP usage for COVID-19 treatment ( 17 , 33 , 34 ), particularly those attributed to the high-titre CCP usage early in the course of the illness ( 13 , 15 , 16 , 23 ). Currently collected data on the CCP treatment of COVID-19 in patients with innate or acquired immunosuppression have been promising and warrant further investigation ( 14 , 18 ).…”