Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection
RCT 86 hospitalized patients, 43 treated with convalescent plasma, showing no significant differences with treatment. Authors conclude that the most likely explanation was already high antibody titers on the day of inclusion, and they recommend treating patients early.
NCT04342182 (history).
risk of death, 3.8% lower, RR 0.96, p = 0.95, treatment 6 of 43 (14.0%), control 11 of 43 (25.6%), NNT 8.6, adjusted per study, odds ratio converted to relative risk, multivariable logistic regression, primary outcome.
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time to discharge, 11.7% lower, relative time 0.88, p = 0.68, treatment 43, control 43, adjusted per study, multivariable Fine and Gray regression.
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Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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Gharbharan et al., 27 May 2020, Randomized Controlled Trial, Netherlands, peer-reviewed, 32 authors, average treatment delay 10.0 days, trial
NCT04342182 (history).
Abstract: ARTICLE
https://doi.org/10.1038/s41467-021-23469-2
OPEN
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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
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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...
Late treatment
is less effective
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