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

Franchini, Massimo; Corsini, Francesco; Focosi, Daniele; Cruciani, Mario

doi:10.3390/diagnostics11091663

Cited by 23 publications

(25 citation statements)

References 72 publications

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“…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 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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During the ongoing COVID-19 epidemic many efforts have gone into the investigation of the SARS-CoV-2–specific antibodies as possible therapeutics. Currently, conclusions cannot be drawn due to the lack of standardization in antibody assessments. Here we describe an approach of establishing antibody characterisation in emergent times which would, if followed, enable comparison of results from different studies. The key component is a reliable and reproducible assay of wild-type SARS-CoV-2 neutralisation based on a banking system of its biological components - a challenge virus, cells and an anti-SARS-CoV-2 antibody in-house standard, calibrated to the First WHO International Standard immediately upon its availability. Consequently, all collected serological data were retrospectively expressed in an internationally comparable way. The neutralising antibodies (NAbs) among convalescents ranged from 4 to 2869 IU mL-1 in a significant positive correlation to the disease severity. Their decline in convalescents was on average 1.4-fold in a one-month period. Heat-inactivation resulted in 2.3-fold decrease of NAb titres in comparison to the native sera, implying significant complement activating properties of SARS-CoV-2 specific antibodies. The monitoring of NAb titres in the sera of immunocompromised COVID-19 patients that lacked their own antibodies evidenced the successful transfusion of antibodies by the COVID-19 convalescent plasma units with NAb titres of 35 IU mL-1 or higher.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Franchini

Glingani

Donno

et al. 2022

Life

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In Winter 2020, Italy, and in particular the Lombardy region, was the first country in the Western hemisphere to be hit by the COVID-19 pandemic. Plasma from individuals recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first therapeutic tool adopted to counteract the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this retrospective cohort study, we report the experience of the city hospital of Mantua, Lombardy region, on the compassionate use of CCP in patients hospitalized for severe COVID-19. Between April 2020 and April 2021, 405 consecutive COVID-19 patients received 657 CCP units with a median anti-SARS-CoV-2 neutralizing antibody (nAb) titer of 160 (interquartile range (IQR), 80–320). Their median age was 68 years (IQR, 56–78 years), and 62% were males. At enrollment, 55% of patients had an increased body mass index (BMI), and 25.6% had at least three comorbidities. The 28-day crude mortality rate was 12.6% (51/405). Young age (<68 years), mild disease (admission to low-intensity departments) and early treatment (<7 days from symptoms onset) with high nAb titer (≥320) CCP were found as independently associated with a favorable response to CCP treatment. No safety concerns were recorded, with a rate of CCP-related adverse reactions (all of mild intensity) of 1.3%. In our real-life experience, the first in the western world, early administration of high-titer CCP was a safe and effective treatment for hospitalized COVID-19 patients.

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“…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).…”

Section: Resultsmentioning

confidence: 99%

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

Focosi¹,

Franchini

Pirofski

et al. 2021

Preprint

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Convalescent plasma (CP) recurs as a frontline treatment in epidemics because it is available as soon as there are survivors. The COVID-19 pandemic represented the first large-scale opportunity to shed light into mechanisms of action, safety and efficacy of convalescent plasma using modern evidence-based medicine approaches. Studies ranging from observational case series to randomized controlled trials (RCT) have reported highly variable efficacy results for COVID-19 CP (CCP), resulting in more doubt than certainty. Reasons for CCP success and failure may be hidden in study details, which are usually difficult to explain to physicians and the public but provide fertile ground for designing next-generation studies. In this paper we analyzed variables associated with efficacy such as clinical settings, disease severity, CCP SARS-CoV-2 antibody levels and function, dose, timing of administration (variously defined as time from onset of symptoms, molecular diagnosis, diagnosis of pneumonia, or hospitalization, or by serostatus), outcomes (defined as hospitalization, requirement for ventilation, clinical improvement or mortality), CCP provenance and time for collection, and criteria for efficacy. Focusing only on the results from the 23 available RCT we noted that these were more likely to show signals of efficacy, including reductions in mortality, if the plasma neutralizing titer was ≥ 160 and the time to randomization was ≤ 9 days, consistent with passive antibody therapy efficacy requiring dosing with sufficient antibody. The fact that most studies revealed signals of efficacy despite variability in CCP and its use suggest robust therapeutic effects that become apparent despite the data noise.

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

Cited by 23 publications

References 72 publications

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

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

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

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

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