Convalescent Plasma for the Prevention and Treatment of COVID-19: A Systematic Review and Quantitative Analysis (Preprint)
BACKGROUND The coronavirus disease (COVID-19) pandemic caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread quickly worldwide. Currently, no vaccine or specific therapeutics are available to prevent and/or treat COVID-19. Convalescent plasma (CP) obtained from patients following resolution of 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. OBJECTIVE We sought to characterize the latest advances and evidence in the use of CP for COVID-19 through a systematic review and quantitatively analysis, identify knowledge gaps in this setting, and offer recommendations and directives for future research. METHODS PubMed, Web of Science and Embase were continuously searched for studies assessing the use of CP for COVID-19 including clinical studies, commentaries, reviews, guidelines/protocols and in vitro testing of CP antibodies. Screening process and data extraction were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Quality appraisal of all clinical studies was conducted using an universal tool independent on study designs. Meta-analysis of case-controlled and randomized controlled trials (RCTs) was conducted using a random-effects model. RESULTS Substantial 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, 35 in vitro testing of CP antibodies, matched the criteria. Positive results have been mostly observed so far when utilising CP for the treatment of COVID-19. There are remarkable heterogeneities in the CP therapy with respect to patient demographics, donor antibody titers, 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 one RCT was of high quality. Randomized and non-randomized data were found in two and 11 studies, respectively and 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. CONCLUSIONS There 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 COVID-19 patients. Future research is necessary to fill the knowledge gap regarding prevention and treatment of COVID-19 patients with CP while vaccines and other treatment are being developed.