Early versus deferred anti-SARS-CoV-2 convalescent plasma in patients admitted for COVID-19: A randomized phase II clinical trial
María Elvira Balcells, Luis Rojas, Nicole Le Corre, Constanza Martínez-Valdebenito, María Elena Ceballos, Marcela Ferrés, Mayling Chang, Cecilia Vizcaya, Sebastián Mondaca, Álvaro Huete, Ricardo Castro, Mauricio Sarmiento, Luis Villarroel, Alejandra Pizarro, Patricio Ross, Jaime Santander, Bárbara Lara, Marcela Ferrada, Sergio Vargas-Salas, Carolina Beltrán-Pavez, Ricardo Soto-Rifo, Fernando Valiente-Echeverría, Christian Caglevic, Mauricio Mahave, Carolina Selman, Raimundo Gazitúa, José Luis Briones, Franz Villarroel-Espindola, Carlos Balmaceda, Manuel A Espinoza, Jaime Pereira, Bruno Nervi
PLOS Medicine, doi:10.1371/journal.pmed.1003415
Background Convalescent plasma (CP), despite limited evidence on its efficacy, is being widely used as a compassionate therapy for hospitalized patients with COVID-19. We aimed to evaluate the efficacy and safety of early CP therapy in COVID-19 progression.
Methods and findings The study was an open-label, single-center randomized clinical trial performed in an academic medical center in Santiago, Chile, from May 10, 2020, to July 18, 2020, with final follow-up until August 17, 2020. The trial included patients hospitalized within the first 7 days of COVID-19 symptom onset, presenting risk factors for illness progression and not on mechanical ventilation. The intervention consisted of immediate CP (early plasma group)
Supporting information [22] ). (B) CT score 2 (Yang et al. [25] ). (C) CT score 3 (Pan et al. [23, 24] ). (TIF)
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References
Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the treatment of Covid-19-final report, N Engl J Med,
doi:10.1056/NEJMoa2007764
Beltra ´n-Pavez, Riquelme-Barrios, Oyarzu ´n-Arrau, Gaete-Argel, Gonza ´lez-Stegmaier et al., Insights into neutralizing antibodies responses in individuals exposed to SARS-CoV-2 in Chile, Sci Adv
Borobia, Carcas, Arnalich, ´lvarez-Sala, Monserrat-Villatoro et al., A cohort of patients with COVID-19 in a major teaching hospital in Europe, J Clin Med,
doi:10.3390/jcm9061733
Cheng, Wong, Soo, Wong, Lee et al., Use of convalescent plasma therapy in SARS patients in Hong Kong, Eur J Clin Microbiol Infect Dis,
doi:10.1007/s10096-004-1271-9
Duan, Liu, Li, Zhang, Yu et al., Effectiveness of convalescent plasma therapy in severe COVID-19 patients, Proc Natl Acad Sci U S A,
doi:10.1073/pnas.2004168117
Garg, Kim, Whitaker, 'halloran, Cummings et al., Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019-COVID-NET, 14 states, MMWR Morb Mortal Wkly Rep,
doi:10.15585/mmwr.mm6915e3
Gharbharan, Jordans, Geurtsvankessel, Hollander, Karim et al., Convalescent plasma for COVID-19. A randomized clinical trial, medRxiv,
doi:10.1101/2020.07.01.20139857
Guan, Ni, Hu, Liang, Ou et al., Clinical characteristics of coronavirus disease 2019 in China, N Engl J Med,
doi:10.1056/NEJMoa2002032
Hung, To, Lee, Lee, Chan et al., Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection, Clin Infect Dis,
doi:10.1093/cid/ciq106
Ji, Zhang, Xu, Chen, Yang et al., Prediction for progression risk in patients with COVID-19 pneumonia: the CALL score, Clin Infect Dis,
doi:10.1093/cid/ciaa414
Joyner, Bruno, Klassen, Kunze, Johnson et al., Safety update: COVID-19 convalescent plasma in 20,000 hospitalized patients, Mayo Clin Proc,
doi:10.1016/j.mayocp.2020.06.028
Joyner, Senefeld, Klassen, Mills, Johnson et al., Effect of convalescent plasma on mortality among hospitalized patients with COVID-19: initial three-2 month experience, medRxiv,
doi:10.1101/2020.08.12.20169359
Ko, Seok, Cho, Ha, Baek et al., Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience, Antivir Ther,
doi:10.3851/IMP3243
Li, Zhang, Hu, Tong, Zheng et al., Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial, JAMA,
doi:10.1001/jama.2020.10044
Liu, Lin, Baine, Wajnberg, Gumprecht et al., Convalescent plasma treatment of severe COVID-19: a propensity score-matched control study, Nat Med,
doi:10.1038/s41591-020-1088-9
Mair-Jenkins, Saavedra-Campos, Baillie, Cleary, Khaw et al., 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,
doi:10.1093/infdis/jiu396
Ministerio, de Salud de Chile. Esta ´ndares para la obtencio ´n de componentes sanguı ´neos y gestio ´n de stock
O ¨zdemir O ¨, Arsoy, Convalescent (immune) plasma therapy with all aspects: yesterday, today and COVID-19, Erciyes Med J,
doi:10.14744/etd.2020.36528
Pan, Ye, Sun, Gui, Liang et al., Time course of lung changes at chest CT during recovery from Coronavirus disease 2019 (COVID-19), Radiology,
doi:10.1148/radiol.2020200370
Pan, Zheng, Ye, Li, Liu et al., Different computed tomography patterns of Coronavirus Disease 2019 (COVID-19) between survivors and non-survivors, Sci Rep,
doi:10.1038/s41598-020-68057-4
Polidoro, Hagan, De, Santiago, Schmidt, Overview: systemic inflammatory response derived from lung injury caused by SARS-CoV-2 infection explains severe outcomes in COVID-19, Front Immunol,
doi:10.3389/fimmu.2020.01626
Raoufi, Naini, Azizan, Zade, Shojaeian et al., Correlation between chest computed tomography scan findings and mortality of COVID-19 cases; a cross sectional study, Arch Acad Emerg Med,
doi:10.22037/aaem.v8i1.719
Recovery Collaborative Group, Horby, Lim, Emberson, Mafham et al., Dexamethasone in hospitalized patients with Covid-19-preliminary report, N Engl J Med,
doi:10.1056/NEJMoa2021436
Richardson, Hirsch, Narasimhan, Crawford, Mcginn et al., Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area, JAMA,
doi:10.1001/jama.2020.6775
Sarzotti-Kelsoe, Bailer, Turk, Lin, Bilska et al., Optimization and validation of the TZM-bl assay for standardized assessments of neutralizing antibodies against HIV-1, J Immunol Methods,
doi:10.1016/j.jim.2013.11.022
Schmidt, Weisblum, Muecksch, Hoffmann, Michailidis et al., Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses, J Exp Med,
doi:10.1084/jem.20201181
Shen, Wang, Zhao, Yang, Li et al., Treatment of 5 critically ill patients with COVID-19 with convalescent plasma, JAMA,
doi:10.1001/jama.2020.4783
Thevarajan, Nguyen, Koutsakos, Druce, Caly et al., Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19, Nat Med,
doi:10.1038/s41591-020-0819-2
Vlaar, Toy, Fung, Looney, Juffermans et al., A consensus redefinition of transfusion-related acute lung injury, Transfusion,
doi:10.1111/trf.15311
Yang, Li, Liu, Zhen, Zhang et al., Chest CT severity score: an imaging tool for assessing severe COVID-19, Radiol Cardiothorac Imaging,
doi:10.1148/ryct.2020200047
Ye, Fu, Ren, Wang, Wang et al., Treatment with convalescent plasma for COVID-19 patients in Wuhan, China, J Med Virol,
doi:10.1002/jmv.25882
Zhang, Gan, Zhen, Hu, Li et al., Adaptive immune responses to SARS-CoV-2 infection in severe versus mild individuals, Signal Transduct Target Ther,
doi:10.1038/s41392-020-00263-y
Zhou, Yu, Du, Fan, Liu et al., Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet,
doi:10.1016/S0140-6736%2820%2930566-3
Zhou, Zhu, Wang, Xia, Imaging features and evolution on CT in 100 COVID-19 pneumonia patients in Wuhan, China, Eur Radiol,
doi:10.1007/s00330-020-06879-6