Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients
Authors: Millat-Martinez Pere , Gharbharan Arvind , Alemany Andrea , Rokx Casper , Geurtsvankessel Corine , Papageorgiou Grigorios , van Geloven Nan , Jordans Carlijn , Groeneveld Geert , Swaneveld Francis , van der Schoot Ellen , Corbacho-Monné Marc , Ouchi Dan , Piccolo Ferreira Francini , Malchair Pierre , Videla Sebastian , García García Vanesa , Ruiz-Comellas Anna , Ramírez-Morros Anna , Rodriguez Codina Joana , Amado Simon Rosa , Grifols Joan-Ramon , Blanco Julian , Blanco Ignacio , Ara Jordi , Bassat Quique , Clotet Bonaventura , Baro Bàrbara , Troxel Andrea , Zwaginga Jaap Jan , Mitjà Oriol , Rijnders Bart J. A. ,   CoV-Early study group, Gharbharan Arvind , Rokx Casper , Jordans Carlijn , Geurtsvankessel Corine , Papageorgiou Grigorios , Rijnders Bart , Katsikis Peter , Müller Yvonne , Koopmans Marion , Bogers Susanne , Miedema Jelle , Russcher Henk , Scherpenisse Cees , van Engen Rene , Karisli Ayten , Götz Hannelore , Struik Jelle , Rokx-Niemantsverdriet Lotte , van Geloven Nan , Groeneveld Geert , Jan Zwaginga Jaap , Zwaginga Lisa , Oud Josine , Meier Romy , van Zwet Erik , Mooijaart Simon , Albersen Arjan , Swaneveld Francis , van der Schoot Ellen , Vrielink Hans , van de Watering Leo , Hogema Boris , van Wijngaarden Peter , van Etten Ronald , van Gammeren Adriaan , Maas Nanda , van Ginneken Betty , den Hollander Jan , Verstijnen Jose , van den Berg – Rahman Juliette , Karim Faiz , Hiddema Siepke , van Elst Kim , van Leeuwen-Segarceanu Elena , Reitsma Annette , Molenkamp Karin , Soetekouw Robert , Band Caterina , de Droog José , Lammers Jolanda , Buitenhuis Lonneke , Postma Douwe , Koster David , Lukens Michaèl , Scholtens Thea , van den Boomgaard Maartje , Vonk Machiel , Kampschreur Linda , van Vonderen Marit , Vrolijk Loes , Reusken Chantal , Reimerink Johan , Harvala Heli ,   COnV-ert study group, Alemany Andrea , Corbacho-Monné Marc , Ouchi Dan , Clotet Bonaventura , Mitjà Oriol , Costes Gèlia , Capdevila-Jáuregui Mar , Torrano-Soler Pamela , San José Alba , Jiménez Zahida , Ramírez-Viaplana Ferran , Ferrer Susana , Gallardo Mireia , Ubals Maria , González-Beiras Camila , Vall-Mayans Martí , Rodriguez-Arias Miquel Angel , Suñer Clara , Puig Jordi , Nieto Aroa , Galvan-Femenia Ivan , Comas-Leon Xavier , Millat-Martínez Pere , Bassat Quique , Baro Bàrbara , Blanco Ignacio , Ara Jordi , Bonet Papell Glòria , Delgado Capel Maria , Díez Sánchez Beatriz , Pons Barber Maria , Gonzalez Ruiz Cristian , Navarrete Gonzalez Laura , González García David , Vivero Larraza Ainhoa , Carceles Peiró Victor , Roquer López Clàudia , Ferrer Magí , Malchair Pierre , Videla Sebastian , García García Vanesa , Gudiol Carlota , Otero Aurema , Ruibal Suarez Jose Carlos , Pellejero Alvaro Zarauza , Llopis Roca Ferran , Rodriguez Cortez Orlando , Casares Gonzalez Pablo , Arcos Vila Gemma , Flores Aguilera Begoña , Rodríguez-Sevilla Graciela , Dastis Arias Macarena , Ruiz-Comellas Anna , Ramírez-Morros Anna , Roca Font Judit , Carrasco Matos Katherine M. , Saüch Valmaña Glòria , Vidal Obradors Carla , Rodríguez Codina Joana , Amado Simon Rosa , Tarres García Silvia , Curriu Sabatès Margarida , Nieto Rodríguez Raquel , Grífols Joan-Ramon , Millan Anna , Contreras Enric , Ancochea Àgueda , Línio Rosa , Fornos Miriam , Casamitjana Natàlia , Alonso Eva , Martinez Núria , Maglio Laura Analía , Comellas Fernandez Laura , Garcia Nadia , Hernández Luis , González María Isabel , Bravo Anna , García Yolanda , Prat Núria , Verdaguer Joaquim , Vértiz Guidotti Thatiana , Benavent Sergio , Bianco Andrea Sofia , Briones Zambrano Ney Nicanor , Viozquez Meya Maria , Forcada Anna , Vidal-Alaball Josep , Giménez Montserrat , París Alexa , Fernández Rivas Gema , Casañ Lopez Cristina , Hernández Águeda , Bordoy Antoni E. , González Soler Victoria , Blanco Julian , Pradenas Edwars , Marfil Silvia , Trinité Benjamin , Piccolo Ferreira Francini , Bonet Mireia , Cantoni Jordi , Marks Michael 
Published: May 2022

AbstractData on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved. A Bayesian-adaptive individual patient data meta-analysis was implemented. Outpatients aged ≥50 years and symptomatic for ≤7days were included. The intervention consisted of 200–300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667–1.311); OR for hospitalization or death was 0.919 (CI 0.592–1.416). CP effect on hospital admission or death was largest in patients with ≤5 days of symptoms (OR 0.658, 95%CI 0.394–1.085). CP did not decrease the time to full symptom resolution.Trial registration: Clinicaltrials.gov NCT04621123 and NCT04589949. Registration: NCT04621123 and NCT04589949 on https://www.clinicaltrials.gov