Convalescent Plasma Transfusion for Treatment of Corona Virus Disease 2019 (COVID-19) Infection: A Systematic Review

Abstract

Abstract Background and object The coronavirus disease 2019 (COVID-19) represents a major global challenge with more than 200 million confirmed cases and over 4.5 million deaths till now. Unfortunately, therapeutic options are still limited and under trial. Convalescent plasma (CP) has emerged as a treatment modality based on previous use in similar viral outbreaks and early clinical trials, but there is still a controversy regarding its efficacy in COVID-19 patients. The aim of this systematic review is to examine evidence on the value of CP as a potential therapy for COVID-19 patients. Methods The current review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. A literature search was conducted on multiple databases including Medline/PubMed, Web of Science, Cochrane library, Wiley Online Library, Scopus and Google Scholar. Databases were searched for eligible studies using the following keywords: COVID-19, novel corona virus, SARS-COV-2, convalescent plasma, and convalescent plasma therapy (CPT). Data extraction and risk of bias assessments were performed by independent two reviewers. Clinical studies comparing CP combined with standard treatment for COVID-19 versus standard treatment only were eligible, including RCTs, non-randomized clinical trials (NRCTs) and case series. We only included studies published in English but there was no restriction on the year of publication, country where study was conducted or age or sex of patients. The primary outcome was mortality rate. Secondary outcomes were time to clinical improvement, need for mechanical ventilation, intensive care or hospital length of stay and incidence of transfusion-related adverse outcomes. Results Based on the selection criteria, 23 articles were eligible including 8 RCTs and 15 controlled nonrandomized studies of interventions (NRSIs). Nearly all RCTs had low risk of bias. However, the risk of bias was considered to be high in all NRSIs. Our review showed that CP reduced overall mortality significantly in only 3 RCTs and 5 NRSIs and improved clinical outcomes significantly in only one RCT and 6 NRSIs. The time to clinical improvement, ICU stay, and need for mechanical ventilations were significantly better in CP groups in limited numbers of studies. The overall incidence of severe transfusionrelated adverse outcomes was low. Conclusions Current evidence regarding the benefit of CP in moderate to severe COVID-19 is nonconclusive. Most evidence is derived from NRSI that suffer from significant risk of bias. Evidence from RCTs carries low risk of methodological bias but clinical benefit of CP is inconsistent across studies. CP seems to be associated with no increased risk of serious transfusion-related adverse outcome. More welldesigned RCTs are still needed to elucidate the actual role of CP in patients with COVID-19.