Abstract: ARTICLE https://doi.org/10.1038/s41467-021-23469-2 OPEN 1234567890():,; Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection Arvind Gharbharan1,16, Carlijn C. E. Jordans1,16, Corine GeurtsvanKessel 1, Jan G. den Hollander2, Faiz Karim3, Femke P. N. Mollema4, Janneke E. Stalenhoef – Schukken 5, Anthonius Dofferhoff6, Inge Ludwig7, Adrianus Koster8, Robert-Jan Hassing9, Jeannet C. Bos10, Geert R. van Pottelberge11, Imro N. Vlasveld12, Heidi S. M. Ammerlaan13, Elena M. van Leeuwen – Segarceanu14, Jelle Miedema1, Menno van der Eerden1, Thijs J. Schrama 1, Grigorios Papageorgiou1, Peter te Boekhorst1, Francis H. Swaneveld15, Yvonne M. Mueller 1, Marco W. J. Schreurs1, Jeroen J. A. van Kampen1, Barry Rockx 1, Nisreen M. A. Okba 1, Peter D. Katsikis 1, Marion P. G. Koopmans 1, Bart L. Haagmans 1, Casper Rokx 1,16 ✉ & Bart J. A. Rijnders1,16 In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARSCoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARSCoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development. 1 Erasmus MC, University Medical Center, Rotterdam, The Netherlands. 2 Maasstad Hospital, Rotterdam, The Netherlands. 3 Groene Hart Hospital, Gouda, The Netherlands. 4 Haaglanden Medical Center, The Hague, The Netherlands. 5 OLVG Hospital, Amsterdam, The Netherlands. 6 Canisius Wilhelmina Hospital, Nijmegen, The Netherlands. 7 Bernhoven Hospital, Uden, The Netherlands. 8 Viecuri Medical Center, Venlo, The Netherlands. 9 Rijnstate Hospital, Arnhem, The Netherlands. 10 Reinier de Graaf Gasthuis, Delft, The Netherlands. 11 ZorgSaam Hospital, Terneuzen, The Netherlands. 12 Martini Hospital, Groningen, The Netherlands. 13 Catharina Hospital, Eindhoven, The Netherlands. 14 Sint Antonius Hospital, Nieuwegein, The Netherlands. 15 Unit of Transfusion Medicine, Sanquin Blood Supply, Amsterdam, The Netherlands. 16These authors contributed equally: Arvind Gharbharan, Carlijn C.E. Jordans, Casper Rokx, Bart J.A. Rijnders. ✉email: c.rokx@erasmusmc.nl NATURE COMMUNICATIONS | (2021)12:3189 | https://doi.org/10.1038/s41467-021-23469-2 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-021-23469-2 S evere acute respiratory syndrome coronavirus 2 (SARSCoV-2), the cause of coronavirus disease 2019 (COVID-19), continues to put a tremendous strain on healthcare systems despite the advances that were made regarding the management of these patients. Anti-inflammatory therapy with dexamethasone significantly decreased mortality1...