Convalescent or standard plasma versus standard of care in the treatment of COVID-19 patients with respiratory impairment: short and long-term effects. A three-arm randomized controlled clinical trial
Authors: Manzini Paola Maria , Ciccone Giovannino , De Rosa Francesco Giuseppe , Cavallo Rossana , Ghisetti Valeria , D’Antico Sergio , Galassi Claudia , Saccona Fabio , Castiglione Anna , Birocco Nadia , Francisci Tiziana , Hu Huijing , Pecoraro Clara , Danielle Franca , Labanca Luciana , Bordiga Anna Maria , Lorenzi Marco , Camisasca Giovanni , Giachino Osvaldo , Pagliarino Mauro , Ottone Piero , Scuvera Ilvana Tiziana Donatella , Guaschino Roberto , Freilone Roberto , Berti Pierluigi , Pittaluga Fabrizia , Avolio Maria , Costa Cristina , Raso Samuele , Nucci Aurora , Milan Massimo , Baffa Alessandra , Russo Alessandra , Tornello Antonella , Maddalena Laura , Delios Grazia , Marletto Fabio Paolo , De Micheli Anna Grazia , Mattei Alessio , Baldassano Stefano , Canta Francesca , Russo Maria Luisa , Bergamo Daniele , Vitale Francesco , Liccardi Marco Maria , Chinaglia Alessandra , Calcagno Andrea , Converso Marcella , Aldieri Chiara , Libanore Valentina , Blangetti Ilaria , Benedetti Valentina , Mitola Barbara , Scozzari Gitana ,   the PLACO COVID Study Group, Castagno Franco , Valfrè Adriano , Rizzioli Gabriella , D’Amato Teresa , Crocillà Cristina , Naselli Silvana , Granero Valentino , Cornagliotto Grazia , Lucania Graziella , Scaglia Cristiana , Ferro Francesca , Solimine Carmela , Ricotti Monica , Gilestro Cristina , Roncato Remigio , Palladino Angela , Ongaro Daniela , Poggio Giulia Anna , Chiappero Chiara , Pinna Simone Mornese , Scabini Silvia , Vischia Federico , Gregoretti Maria Grazia , Lupia Enrico , Brazzi Luca , Albera Carlo , Scaglione Luca , Gallo Valter , Norbiato Claudio , Albiani Roberto , Sini Bruno Lucio , Fassiola Andrea , Locatelli Alessandro , Di Perri Giovanni , Navarra Mauro , Gardini Isabella , Ciardiello Aurora , La Grotta Rita , De Rosa Anna , Pasquino Paola , Fiore Gilberto , Franza Orietta , Artoni Paola , Meinardi Stefano , Calosso Liliana , Molino Paola , Veglio Maria Grazia , Beltramo Tiziana , Camerini Odetta , Giancaspero Karol , Napoli Franca , Perboni Alberto , Messa Emanuela , Buffolo Fabrizio , Pagnozzi Fiammetta , Bertone Stefania , Lutri Lorenzo , Gravante Umberto , Sacchetti Petros , Pavan Alessandra , Castenetto Enzo , Novelli Marco , Tucciarone Marco , Ocello Patrizia , Guido Giulia , Frascaroli Chiara , Vivenza Daniela Maria Luisa , Patti Francesca , Lorenzelli Laura , Balduzzi Guido , Ratti Deborah , Mazzucco Laura , Balbo Valeria , Pollis Francesca , Leoncino Sabrina , Lupo Chiara , Romano Daniele , Ziccardi Silvia , Marmifero Melania , Chichino Guido , Salio Mario , Aiosa Giuseppe , Boverio Riccardo , Avonto Ilaria , Ghiotto Sara , Balbo Riccardo , Nico Vincenza , Aguzzi Chiara , Pellegrino Maria Chiara , Prucca Maristella , Longa Lucia Assunta , Perotti Laura , Piovano Federica , Ambrogio Luca , Formica Marco , Monge Elisa , Arena Flavia , Barzaghi Nicoletta , Tavera Silvia , Canepari Mariaelisa , Strani Guido , Pomero Fulvio , Cianci Maria Grazia , Gianarda Mariella , Ruscitto Leonardo , De Martino Daniel , Macchi Sandro , Montagnana Michele , Grandinetti Vladimiro , Magnani Silvia , Radin Elisabetta , Pellu Valentina , Meucci Monica , Noè Erika , Torti Paola , Montagnani Luca , Doveri Giulio , Giustetto Gabriella , Avdis Costantino , Prina Marco , Eliantonio Franco , Lemut Francesco , Semino Giuseppe , Spidalieri Palmina , Vallino Domenico , Prota Roberto , Buono Gabriella , Segala Vincenzo , Milia Maria Grazia , Aprà Franco , Livigni Sergio , Manno Emilpaolo , Caula Giuseppe , Vitali Emanuela , Liuzzi Nicola , Pastorelli Mauro , Caironi Pietro , Gamna Federica , Scapino Bruno , Gurioli Lorenzo , Magro Emanuele , Roberti Giuseppe , Santamaria Gian Mario , Daffonchio Antonella , Varese Paola , Ghiazza Gianfranco , Girino Margherita , Pelazza Carolina , Racca Fabrizio , Grillo Mirco , Del Bono Valerio , Gianotto Giorgio , Aluffi Enzo , Ravera Enrico 
Published: November 2022

Abstract
Background
The efficacy of early treatment with convalescent plasma in patients with COVID-19 is debated. Nothing is known about the potential effect of other plasma components other than anti-SARS-CoV-2 antibodies.

Methods
To determine whether convalescent or standard plasma would improve outcomes for adults in early phase of Covid19 respiratory impairment we designed this randomized, three-arms, clinical trial (PLACO COVID) blinded on interventional arms that was conducted from June 2020 to August 2021. It was a multicentric trial at 19 Italian hospitals. We enrolled 180 hospitalized adult patients with COVID-19 pneumonia within 5 days from the onset of respiratory distress. Patients were randomly assigned in a 1:1:1 ratio to standard of care (n = 60) or standard of care + three units of standard plasma (n = 60) or standard of care + three units of high-titre convalescent plasma (n = 60) administered on days 1, 3, 5 after randomization. Primary outcome was 30-days mortality. Secondary outcomes were: incidence of mechanical ventilation or death at day 30, 6-month mortality, proportion of days with mechanical ventilation on total length of hospital stay, IgG anti-SARS-CoV-2 seroconversion, viral clearance from plasma and respiratory tract samples, and variations in Sequential Organ Failure Assessment score. The trial was analysed according to the intention-to-treat principle.

Results
180 patients (133/180 [73.9%] males, mean age 66.6 years [IQR 57–73]) were enrolled a median of 8 days from onset of symptoms. At enrollment, 88.9% of patients showed moderate/severe respiratory failure. 30-days mortality was 20% in Control arm, 23% in Convalescent (risk ratio [RR] 1.13; 95% confidence interval [CI], 0.61–2.13, P = 0.694) and 25% in Standard plasma (RR 1.23; 95%CI, 0.63–2.37, P = 0.544). Time to viral clearance from respiratory tract was 21 days for Convalescent, 28 for Standard plasma and 23 in Control arm but differences were not statistically significant. No differences for other secondary endpoints were seen in the three arms. Serious adverse events were reported in 1.7%, 3.3% and 5% of patients in Control, Standard and Convalescent plasma arms respectively.

Conclusions
Neither high-titer Convalescent nor Standard plasma improve outcomes of COVID-19 patients with acute respiratory failure.
Trial Registration Clinicaltrials.gov Identifier: NCT04428021. First posted: 11/06/2020