Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial)
Karin Van Den Berg, Tanya Nadia Glatt, Marion Vermeulen, Francesca Little, Ronel Swanevelder, Claire Barrett, Richard Court, Marise Bremer, Cynthia Nyoni, Avril Swarts, Cordelia Mmenu, Thomas Crede, Gerdien Kritzinger, Jonathan Naude, Patryk Szymanski, James Cowley, Thandeka Moyo-Gwete, Penny L Moore, John Black, Jaimendra Singh, Jinal N Bhiman, Prinita Baijnath, Priyesh Mody, Jacques Malherbe, Samantha Potgieter, Cloete Van Vuuren, Shaun Maasdorp, Robert J Wilkinson, Vernon J Louw, Sean Wasserman
Scientific Reports, doi:10.1038/s41598-022-06221-8
There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma
www.nature.com/scientificreports/ definitive conclusions, absence of a major safety signal is somewhat reassuring. In line with experience in other settings 11 , CCP use was safe in our overall cohort, supporting future evaluation for different indications in high HIV burden populations. The premature termination of the PROTECT trial illustrates the complexity of undertaking clinical research in a rapidly evolving global pandemic. Inconsistent case numbers, viral evolution, and rapidly changing evidence during the trial period contributed to this challenge. Despite this, our trial demonstrated the feasibility of deploying CCP in a resource-limited setting and contributed knowledge on the use of this therapeutic strategy for COVID-19 pneumonia. Our experience highlights the necessity of globally networked clinical trial sites and harmonised study protocols to more efficiently evaluate interventions among diverse populations during a pandemic.
Competing interests The authors declare no competing interests.
References
Agarwal, Convalescent plasma in the management of moderate covid-19 in adults in India: Open label phase II multicentre randomised controlled trial (PLACID Trial), BMJ
Amanat, A serological assay to detect SARS-CoV-2 seroconversion in humans, Nat. Med
Axfors, Association between convalescent plasma treatment and mortality in COVID-19: A collaborative systematic review and meta-analysis of randomized clinical trials, BMC Infect. Dis
Bajpai, Kumar, Maheshwari, Efficacy of convalescent plasma therapy compared to fresh frozen plasma in severely ill COVID-19 patients: A pilot randomized controlled trial, medRxiv,
doi:10.1101/2020.10.25Beigel, Remdesivir for the Treatment of Covid-19-Final Report, N. Engl. J. Med
Bloch, Deployment of convalescent plasma for the prevention and treatment of COVID-19, J. Clin. Investig
Bloch, Guidance for the procurement of COVID-19 convalescent plasma: Differences between high-and low-middleincome countries, Vox Sang
Casadevall, Dadachova, Pirofski, Passive antibody therapy for infectious diseases, Nat. Rev. Microbiol
Chalmers, Abo-Leyah, Loftus, Spears, Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial, Lancet
Duan, Effectiveness of convalescent plasma therapy in severe COVID-19 patients, Proc. Natl. Acad. Sci. U. S. A
González, Regairaz, Salazar, Timing of convalescent plasma administration and 28-day mortality for COVID-19 pneumonia, medRxiv,
doi:10.1101/2021.02.02Guan, Clinical characteristics of coronavirus disease 2019 in China, N. Engl. J. Med
Harris, Research electronic data capture (REDCap)-A metadata-driven methodology and workflow process for providing translational research informatics support, J. Biomed. Inform
Horby, Mafham, Peto, Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Horby, On behalf of the RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19, N. Engl. J. Med
Horny, of the RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19: A randomised controlled, open-label, platform trial, Lancet
Huang, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Joyner, Convalescent plasma antibody levels and the risk of death from Covid-19, N. Engl. J. Med
Joyner, Safety update: COVID-19 Convalescent plasma in 20,000 hospitalized patients, Mayo Clin. Proc
Korley, Early convalescent plasma for high-risk outpatients with Covid-19, N. Engl. J. Med
Kyriazopoulou, Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: A double-blind, randomized controlled phase 3 trial, Nat. Med
Libster, Early high-titer plasma therapy to prevent severe Covid-19 in older adults, N. Engl. J. Med
Ling, Sim, Tan, Convalescent plasma for patients hospitalized with coronavirus disease 2019: A metaanalysis with trial sequential analysis of randomized controlled trials, Transfus Med Rev
Lundgren, On behalf of the Activ-Tico Ly-CoV555 Study Group. A neutralizing monoclonal antibody for hospitalized patients with Covid-19, N. Engl. J. Med
Mair-Jenkins, Saavedra-Campos, Baillie, The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: A systematic review and exploratory meta-analysis, J. Infect. Dis
Marconi, Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): A randomised, double-blind, parallel-group, placebo-controlled phase 3 trial, Lancet Respir. Med
Moyo-Gwete, Cross-reactive neutralizing antibody responses elicited by SARS-CoV-2 501Y.V2 (B.1.351, N. Engl. J. Med
O'donnell, A randomized double-blind controlled trial of convalescent plasma in adults with severe COVID-19, J. Clin. Investig
Recovery Collaborative Group, Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial, Lancet
Rojas, Convalescent plasma in Covid-19: Possible mechanisms of action, Autoimmun. Rev
Senefeld, Therapeutic use of convalescent plasma in COVID-19 patients with immunodeficiency,
doi:10.1101/2020.11.08Shen, Treatment of 5 critically ill patients with COVID-19 with convalescent plasma, JAMA
Simonovich, A randomized trial of convalescent plasma in Covid-19 severe pneumonia, N. Engl. J. Med
Tegally, Detection of a SARS-CoV-2 variant of concern in South Africa, Nature
Wibmer, SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma, Nat. Med
Zhou, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study, Lancet
Zhou, Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera, Cell
