Comparative Analysis of Nine COVID-19 Convalescent Plasma Protocols Registered by Cochrane Central Register of Controlled Trials

Context: Coronavirusdisease 2019 (COVID-19)hasprogressedinto a public health emergency of international concern. Passive immunotherapy has been successfully used for the treatment of infectious diseases since the 1890s. It is necessary and constructive to compare and analyzeCOVID-19 convalescent plasma (CCP) randomized controlled trials (RCTs) to help clinicians to have a potential option for COVID-19.Evidence Acquisition:In this study, eight databases were searched on May 1, 2020, such as China National Knowledge Infrastructure, PubMed, and Cochrane Library, with the search fields of "Title Abstract Keyword" of "Convalescent plasma AND COVID-19" or " Convalescent plasma AND SARS-CoV-2". The outcome of interest was clinical RCTs for COVID-19.

The search retrieved nine relevant CCP protocols for severe acuterespiratory syndromecoronavirus 2(SARS-CoV-2). All nine trials were randomized, parallel assignment, interventional, clinical treatment studies with NCT04344535, NCT04345289, and NCT04323800 masking and the rest open-label. The estimated enrollment is within the range of 40-1,500 subjects, and five trials will be finished in 2020 as opposed to two in 2021 and two in 2022. Except for NCT04323800 on the prevention of COVID-19, other eight trials will test and verify the effectivenessand safety of CCP for the treatment of COVID-19.The used dosage of CCP is within the range of 200-600 mL. NCT04344535, NCT04323800, and NCT04346446 use standard donor plasma incontrolled groups in comparison toNCT04348656, NCT04342182, NCT04333251, and NCT04345523 without anypositive drug in controlled groups. NCT04332835 adds hydroxychloroquineto both groups, and only NCT04345289 is a six-armed placebo-controlled trial.Primary and secondary outcome measures are differently expressed in the nine trials. Nevertheless, they can be summarized as (一)changes in time, day, and number of a 7-point ordinal scale. There are (二)changes in SARS-CoV-2 ribonucleic acid(i.e., viral load), anti-SARS-CoV-2 antibody titers (i.e., immunoglobulin M and immunoglobulin G),C-reactive protein, lymphocyte count, lactate dehydrogenase, and interleukin 6on a specified day or during a specific period.

The nine well-designed RCT trials will establish the efficacy of CCPfor the treatment of SARS-CoV-2from the perspectiveof evidence-based medicine