Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection
Arvind Gharbharan, Carlijn Jordans, Corine H. GeurtsvanKessel, Jan G. den Hollander, Faiz Karim, Femke Mollema, Janneke E. Stalenhoef, Anthonius S. M. Dofferhoff, Inge Ludwig, Adrianus Koster, Robert‐Jan Hassing, Jeannet C. Bos, Geert R. Van Pottelberge, Imro N. Vlasveld, Heidi Ammerlaan, Elena M. van Leeuwen – Segarceanu, Jelle Miedema, Menno M. van der Eerden, Thijs J. Schrama, Grigorios Papageorgiou, Peter A.W. te Boekhorst, Francis Swaneveld, Yvonne M. Mueller, Marco W.J. Schreurs, Jeroen J. A. van Kampen, Barry Rockx, Nisreen M.A. Okba, Peter D. Katsikis, Marion Koopmans, Bart L. Haagmans, Casper Rokx, Bart Rijnders
Abstract
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 SARS-CoV-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 SARS-CoV-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.