Abstract: Original Investigation | Infectious Diseases Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia A Randomized Clinical Trial Francesco Menichetti, MD; Patrizia Popoli, MD; Maria Puopolo, MS; Stefania Spila Alegiani, MS; Giusy Tiseo, MD; Alessandro Bartoloni, MD; Giuseppe Vittorio De Socio, MD; Sauro Luchi, MD; Pierluigi Blanc, MD; Massimo Puoti, MD; Elena Toschi, MS; Marco Massari, MS; Lucia Palmisano, MS; Giuseppe Marano, MD; Margherita Chiamenti, MD; Laura Martinelli, MD; Silvia Franchi, MD; Carlo Pallotto, MD; Lorenzo Roberto Suardi, MD; Barbara Luciani Pasqua, MD; Marco Merli, MD; Plinio Fabiani, MD; Luca Bertolucci, MD; Beatrice Borchi, MD; Sara Modica, MD; Sara Moneta, MD; Giulia Marchetti, MD; 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, MD; Marco Massari, MD; Spartaco Sani, MD; Annalisa Saracino, MD; Antonella Castagna, MD; Luigia Trabace, PhD; Maria Lanza, MD; Daniele Focosi, MD; Alessandro Mazzoni, MD; Mauro Pistello, MD; Marco Falcone, MD; for the TSUNAMI Study group Abstract Key Points IMPORTANCE Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Question Is convalescent plasma useful in preventing worsening respiratory failure or death in patients with OBJECTIVE To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing COVID-19 pneumonia? Findings In this randomized clinical trial worsening respiratory failure or death in patients with COVID-19 pneumonia. of 487 patients with COVID-19 DESIGN, SETTING, AND PARTICIPANTS This prospective, open-label, randomized clinical trial pneumonia and a partial pressure of enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone arterial oxygen–to–fraction of inspired between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 oxygen (PaO2/FiO2) ratio between 350 pneumonia and a partial pressure of oxygen–to–fraction of inspired oxygen (PaO2/FiO2) ratio between and 200 mm Hg at enrollment, the rate 350 and 200 mm Hg were eligible. of the primary clinical end point (need for mechanical ventilation, defined as INTERVENTIONS Patients in the experimental group received intravenous high-titer CP (ⱖ1:160, by PaO2/FiO2 ratio <150 mm Hg, or death) microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum was not significantly different between of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, the convalescent plasma group and the and low–molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. control group. Meaning In this trial, convalescent MAIN OUTCOMES AND MEASURES The primary outcome was a composite of worsening plasma did not reduce the progression respiratory failure (PaO2/FiO2 ratio <150 mm Hg) or death within 30 days from randomization. to severe respiratory failure or death within 30 days. RESULTS Of the 487 randomized patients (241 to CP plus ST;..