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.
Highlights
The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe AcuteRespiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still a worldwide health crisis with devastating social and economic consequences
Inclusion and Exclusion Criteria We considered for inclusion systematic reviews (SRs) that included randomized controlled trials (RCTs) and non-RCTs evaluating the safety and efficacy of Convalescent plasma (CP) in COVID-19 patients
Subgroup analysis according to time to CP transfusion showed a reduction in mortality in early CP recipients compared to controls in three SRs; by contrast a Cochrane review based on a single RCT (RECOVERY trial) [62] concluded that it is unclear whether early CP transfusion reduces mortality compared to controls, transfusion after the first week of illness resulted in higher risk of mortality compared to early transfusion
Summary
The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe AcuteRespiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still a worldwide health crisis with devastating social and economic consequences. Convalescent plasma (CP), first introduced in 1890 by Emil von Behring to treat diphtheria and pertussis and utilized in several other serious infectious diseases, including Ebola, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), has been proposed more recently as passive immunotherapy for treatment of SARS-CoV-2 infection [1]. Convalescent plasma is nowadays among the most studied and utilized antibody-based therapies against COVID-19 world-wide and a number of published or ongoing clinical trials have been conducted to assess its efficacy and safety in this challenging viral infection. Their conclusions are, quite conflicting and reflect the wide heterogeneity between different studies in terms of CP product, patients enrolled, and disease characteristics. To synthesize the evidence from these SRs and meta-analyses, we have decided to apply to this clinical setting a relatively new approach, i.e., to perform an overview of the existing SRs, called umbrella review
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