Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients
Pere Millat-Martínez, Arvind Gharbharan, Andrea Alemany, Casper Rokx, Corine H. GeurtsvanKessel, Grigorios Papageorgiou, Nan van Geloven, Carlijn Jordans, Geert H. Groeneveld, Francis Swaneveld, C. Ellen van der Schoot, Marc Corbacho‐Monné, Dan Ouchi, Francini Piccolo Ferreira, Pierre Malchair, Sebastián Videla, Vanesa García García, Anna Ruiz‐Comellas, Anna Ramírez‐Morros, Joana Rodríguez Codina, Rosa Amado Simon, Joan-Ramon Grífols, Julià Blanco, Ignacio Blanco, Jordi Ara, Quique Bassat, Bonaventura Clotet, Bàrbara Baró, Andrea B. Troxel, Jaap Jan Zwaginga, Oriol Mitjà, Bart Rijnders, CoV-Early study group, Arvind Gharbharan, Casper Rokx, Carlijn Jordans, Corine H. GeurtsvanKessel, Grigorios Papageorgiou, Bart Rijnders, Peter D. Katsikis, Yvonne Müller, Marion Koopmans, Susanne Bogers, Jelle Miedema, Henk Russcher, Cees Scherpenisse, Rene van Engen, Ayten Karisli, Hannelore M Götz, Jelle Struik, Lotte Rokx-Niemantsverdriet, Nan van Geloven, Geert H. Groeneveld, Jaap Jan Zwaginga, Lisa Zwaginga, Josine Oud, Romy Meier, Erik W. van Zwet, Simon P. Mooijaart, Arjan Albersen, Francis Swaneveld, C. Ellen van der Schoot, Hans Vrielink, Leo van de Watering, Boris M. Hogema, Peter van Wijngaarden, Ronald van Etten, Adriaan van Gammeren, Nanda Maas, Betty van Ginneken, Jan den Hollander, Jose Verstijnen, Juliette van den Berg – Rahman, Faiz Karim, Siepke Hiddema, Kim van Elst, Elena van Leeuwen-Segarceanu, Annette Reitsma, Karin Molenkamp, Robert Soetekouw, Caterina Band, José de Droog, Jolanda Lammers, Lonneke Buitenhuis, Douwe F. Postma, David J. Koster, Michaèl Lukens, Thea Scholtens, Maartje van den Boomgaard, Machiel Vonk, Linda M. Kampschreur, Marit van Vonderen, Loes Vrolijk, Chantal Reusken, Johan Reimerink, Heli Harvala, COnV-ert study group, Andrea Alemany, Marc Corbacho‐Monné, Dan Ouchi
Abstract
Data 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.