Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia
MD Francesco Menichetti, MD Patrizia Popoli, MS Maria Puopolo, MS Stefania Spila Alegiani, MD Giusy Tiseo, MD Alessandro Bartoloni, Giuseppe Vittorio De Socio, MD Sauro Luchi, MD Pierluigi Blanc, MD Massimo Puoti, MS Elena Toschi, MS Marco Massari, MS Lucia Palmisano, MD Giuseppe Marano, MD Margherita Chiamenti, MD Laura Martinelli, MD Silvia Franchi, MD Carlo Pallotto, Lorenzo Roberto Suardi, Barbara Luciani Pasqua, MD Marco Merli, MD Plinio Fabiani, MD Luca Bertolucci, MD Beatrice Borchi, MD Sara Modica, MD Sara Moneta, MD Giulia Marchetti, Antonella D’arminio Monforte, MD Laura Stoppini, MD Nadia Ferracchiato, MD Stefania Piconi, MD Claudio Fabbri, MD Enrico Beccastrini, MD Riccardo Saccardi, MD Andrea Giacometti, MD Sara Esperti, MD Piera Pierotti, MD Laura Bernini, MD Claudia Bianco, MD Sara Benedetti, MD Alessandra Lanzi, MD Paolo Bonfanti, MS Marco Massari, MD Spartaco Sani, MD Annalisa Saracino, MD Antonella Castagna, PhD Luigia Trabace, MD Maria Lanza, MD Daniele Focosi, MD Alessandro Mazzoni, MD Mauro Pistello, MD Marco Falcone, Roberto Palazzolo, Salvatore Casari, Alessandro Occhionero, Tiziana Grazzini, Dina Leonarda Silvestri, Mariacarla Iorio, Andrea Tosti, Daniela Francisci, Cecilia Becattini, Matteo Pirro, Mauro Marchesi, Sabrina Bastianelli, Sara Pierucci, Chiara Busti, Antonella Mencacci, Silvia Bozza, Barbara Camilloni, Valentina Annoni, Chiara Bellotto, Adriano Cioppi, Giorgia Querci, Giacomo Ciusa, Michela Tassara, Anna Danise, Silvia Chigiotti, Giovanna Morelli, Micaela Meini, Valentina Galfo, Simone Ferranti, Enrico Tagliaferri, Riccardo Iapoce, Chiara Barbieri, Arianna Forniti, Claudio Caroselli, Stefano Verdenelli, Fabio Monzani, Paola Mazzetti, Giovanna Moscato, Francesco Barchiesi, Mauro Andreotti, Fausto Baldanti, Andrea Binelli, Maria R Capobianchi, Roberto Da Cas, Daniela Di Sevo, Paola Fazi, Cinzia Gasparrini, Ilaria Ippoliti, Alessandra Mancino, Francesca Menniti Ippolito, Francesca Paoloni, Paola Ruggeri, Arianna Rughini, Emanuela Salvi, Valeria Sargentini, Maria P Trotta, Marco Vignetti
JAMA Network Open, doi:10.1001/jamanetworkopen.2021.36246
IMPORTANCE Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. OBJECTIVE To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio between 350 and 200 mm Hg were eligible. INTERVENTIONS Patients in the experimental group received intravenous high-titer CP (Ն1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations.
MAIN OUTCOMES AND MEASURES The primary outcome was a composite of worsening respiratory failure (PaO 2 /FiO 2 ratio <150 mm Hg) or death within 30 days from randomization.
RESULTS Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04).
CONCLUSIONS AND RELEVANCE In patients with moderate to severe COVID-19 pneumonia, hightiter anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. (continued) Key Points Question Is convalescent plasma useful in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia? Findings In this randomized clinical trial of 487 patients with COVID-19 pneumonia and a partial pressure of arterial oxygen-to-fraction of inspired oxygen (PaO 2 /FiO 2 ) ratio between 350 and 200 mm Hg at enrollment, the rate of the primary clinical end point (need for mechanical ventilation, defined as PaO 2 /FiO 2 ratio <150 mm Hg, or death) was not significantly different between the convalescent plasma group and the control group. Meaning In this trial, convalescent plasma did not reduce the progression to severe respiratory failure or death within 30 days.
Conflict of Interest Disclosures: Dr Menichetti reported serving as the principal investigator for an AstraZenecasponsored trial and a Toscana Life Science-sponsored trial evaluating monoclonal antibodies for SARS-CoV-2 (for which no personal fees were received), and receiving speaker honoraria or advisory board or support for meetings from Angelini, Menarini, Correvio, MSD, Pfizer, Astellas, Gilead, BMS, Janssen, ViiV, BioMerieux, Biotest, Becton-Dickinson, Pfizer, Shionogi, Roche, GSK, Advanz Pharma, and ThermoFisher in the last 3 years outside the submitted work. Dr Bartoloni reported receiving study grants from MSD, ViiV Healthcare, and Nordic Pharma and receiving fees for presentations at local congress or expert meetings from Pfizer and MSD in the last 3 years outside the submitted work; Dr Puoti reported receiving personal fees and nonfinancial support from Abbvie, grants and nonfinancial support from Gilead Science, and personal fees from Merck and Theratechnologies outside the submitted work. Dr Marchetti reported receiving grants for lectures, advisory board, or conferences by Gilead, ViiV, and Janssen in the last 3 years outside the submitted work. Dr d'Arminio Monforte reported receiving grants for lectures, advisory board, or conferences by Gilead, ViiV, MSD, Angelini, and Janssen in the last 3 years outside the submitted work; Dr Bonfanti reported receiving personal fees from Viiv, Gilead, Jannsen Pharmaceuticals, Merck, and Pfizer outside the submitted work. Dr..
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