Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis.

Henry T Peng,Shawn G Rhind,Andrew Beckett

doi:10.2196/25500

Abstract

BackgroundThe COVID-19 pandemic, caused by a novel coronavirus termed SARS-CoV-2, has spread quickly worldwide. Convalescent plasma (CP) obtained from patients following recovery from COVID-19 infection and development of antibodies against the virus is an attractive option for either prophylactic or therapeutic treatment, since antibodies may have direct or indirect antiviral activities and immunotherapy has proven effective in principle and in many clinical reports.ObjectiveWe seek to characterize the latest advances and evidence in the use of CP for COVID-19 through a systematic review and quantitative analysis, identify knowledge gaps in this setting, and offer recommendations and directives for future research.MethodsPubMed, Web of Science, and Embase were continuously searched for studies assessing the use of CP for COVID-19, including clinical studies, commentaries, reviews, guidelines or protocols, and in vitro testing of CP antibodies. The screening process and data extraction were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal of all clinical studies was conducted using a universal tool independent of study designs. A meta-analysis of case-control and randomized controlled trials (RCTs) was conducted using a random-effects model.ResultsSubstantial literature has been published covering various aspects of CP therapy for COVID-19. Of the references included in this review, a total of 243 eligible studies including 64 clinical studies, 79 commentary articles, 46 reviews, 19 guidance and protocols, and 35 in vitro testing of CP antibodies matched the criteria. Positive results have been mostly observed so far when using CP for the treatment of COVID-19. There were remarkable heterogeneities in the CP therapy with respect to patient demographics, donor antibody titers, and time and dose of CP administration. The studies assessing the safety of CP treatment reported low incidence of adverse events. Most clinical studies, in particular case reports and case series, had poor quality. Only 1 RCT was of high quality. Randomized and nonrandomized data were found in 2 and 11 studies, respectively, and were included for meta-analysis, suggesting that CP could reduce mortality and increase viral clearance. Despite promising pilot studies, the benefits of CP treatment can only be clearly established through carefully designed RCTs.ConclusionsThere is developing support for CP therapy, particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. These studies provide important lessons that should inform the planning of well-designed RCTs to generate more robust knowledge for the efficacy of CP in patients with COVID-19. Future research is necessary to fill the knowledge gap regarding prevention and treatment for patients with COVID-19 with CP while other therapeutics are being developed.

Highlights

SARS-CoV-2, the cause of COVID-19, was declared a pandemic in early 2020 by the World Health Organization [1,2]
There is developing support for Convalescent plasma (CP) therapy, for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. These studies provide important lessons that should inform the planning of well-designed randomized controlled trial ROM (RCT) to generate more robust knowledge for the efficacy of CP in patients with COVID-19
The theoretical reasons for the likely efficacy of passive immunization, the urgent need felt by clinicians worldwide for effective treatment options for COVID-19, and the promising results offered mainly by retrospective clinical studies must be balanced against the lack of efficacy in the RCTs of CP and hyperimmune globulin therapy in severe influenza and COVID-19

Summary

Introduction

SARS-CoV-2, the cause of COVID-19, was declared a pandemic in early 2020 by the World Health Organization [1,2]. This is the third coronavirus to emerge in the past two decades, causing multinational outbreaks and carrying substantial morbidity and mortality [3]. COVID-19 is characterized by a spectrum of symptoms, ranging from mild subclinical infection with self-limiting respiratory tract illness (dry cough, fever, fatigue, difficulty breathing) to severe progressive manifestations (acute respiratory distress, hypercoagulation, hyperinflammation, multi-organ dysfunction, death) in high-risk patients with known comorbidities (advanced age, diabetes, obesity, cardiopulmonary disease) [4,5]. Convalescent plasma (CP) obtained from patients following recovery from COVID-19 infection and development of antibodies against the virus is an attractive option for either prophylactic or therapeutic treatment, since antibodies may have direct or indirect antiviral activities and immunotherapy has proven effective in principle and in many clinical reports

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