Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection

Arvind Gharbharan, Carlijn C.E. Jordans, Corine Geurts van Kessel, Jan G. den Hollander, Faiz Karim, Femke P.N. Mollema, Janneke E. Stalenhoef – Schukken, Anthonius Dofferhoff, Inge Ludwig, Adrianus Koster, Robert Jan Hassing, Jeannet C. Bos, Geert R. van Pottelberge, Imro N. Vlasveld, Heidi S.M. Ammerlaan, Elena M. van Leeuwen – Segarceanu, Jelle Miedema, Menno van der Eerden, Thijs J. Schrama, Grigorios PapageorgiouPeter te Boekhorst, Francis H. Swaneveld, Yvonne M. Mueller, Marco W.J. Schreurs, Jeroen J.A. van Kampen, Barry Rockx, Nisreen M.A. Okba, Peter D. Katsikis, Marion P.G. Koopmans, Bart L. Haagmans, Casper Rokx*, Bart J.A. Rijnders

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

130 Citations (Scopus)

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.

Original languageEnglish
Article number3189
Pages (from-to)1-9
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 27 May 2021

Bibliographical note

Funding Information:
We thank all plasma donors who volunteered in great numbers and all patients who participated in the study; all colleague internist-infectiologists for giving the study team at Erasmus MC the time to execute this study during unprecedented times; Professor Stephanie Klein-Nagelvoort Schuit, Professor Annelies Verbon, and Professor Charles Boucher, who sadly passed away on 26 February, 2021 for their support; the institutional review board at Erasmus MC for their efficient review of the application and several amendments on short notice; HOVON, in particular Monique Steijaert and Henk Hofwegen, for helping with IRB-related procedures and for programming the ALEA online randomization tool; Aldert Lamore, for programming the eCRF; and Sanquin Blood Supply Netherlands for collecting ConvP from hundreds of donors. We thank the members of the data safety monitoring board Dr. JL Nouwen, Professor H Boersma, and Dr. B Van der Hoven; the Erasmus foundation for financial support, and all those who donated to the foundation for this study, in particular Eduard Haegens and Marleen Hoex from Ypsilon, who made it financially possible to start the trial; Health Holland for the LSHM20056 grant to perform immunological assays; the department of virosciences and the department of immunology (in particular Rik Ruijten, Inge Brouwers - Haspels, Caoimhe Van der Wel – Kiernan, Harm de Wit, Marjan van Meurs, Manzhi Zhao, Melisa Castro Eiro, Merel Wilmsen, Tamara van Wees, and Tessa Alofs), and all laboratory technicians and medical students (in particular Renée Deckers, Freya Huijs-mans, Niek van der Maas, Miliaan Zeelenberg, Zgjim Osmani, Jari Hofmans, and Lieke Heijnen), and Frank van Vliet for helping with real-time data and sample collections throughout the country; and BMW, the Netherlands, for providing two cars free of charge for sample collection. We also thank Dr. Corine Delsing from Medisch Spectrum Twente, Dr. Jiri Wagenaar from Noordwest Ziekenhuisgroep, and Robin Soetekouw from Spaarne Gasthuis for engaging as a study site, all study nurses and trial coordinators in the participating centers, and in particular Siepke Hiddema, Frances Greven, and resident Sander Albers, and many others that volunteered their time and effort for this study.

Funding Information:
The Netherlands Organisation for Health Research and Development (ZonMW, grant agreement 10150062010008, B.L.H.), the Erasmus foundation grant (B.J.A.R.), and the PPP Allowance (grant number LSHM20056, P.D.K.) made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. The remaining authors declare no competing interests.

Publisher Copyright:
© 2021, The Author(s).

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