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0 0.5 1 1.5 2+ Mortality 4% primary Improvement Relative Risk Time to discharge 12% Conv. Plasma  Gharbharan et al.  LATE TREATMENT  RCT Is late treatment with convalescent plasma beneficial for COVID-19? RCT 86 patients in Netherlands (April - June 2020) Trial underpowered for serious outcomes Gharbharan et al., Nature Communications, May 2021 Favors conv. plasma Favors control

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

Gharbharan et al., Nature Communications, doi:10.1038/s41467-021-23469-2, NCT04342182
May 2021  
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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.
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.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Gharbharan et al., 27 May 2021, Randomized Controlled Trial, Netherlands, peer-reviewed, 32 authors, study period 8 April, 2020 - 14 June, 2020, average treatment delay 10.0 days, trial NCT04342182 (history).
This PaperConv. PlasmaAll
Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection
Arvind Gharbharan, Carlijn C E Jordans, Corine Geurtsvankessel, 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 Papageorgiou, Peter 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
Nature Communications, doi:10.1038/s41467-021-23469-2
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.
Author contributions Competing interests The Additional information Supplementary information The online version contains supplementary material available at Correspondence and requests for materials should be addressed to C.R. Reprints and permission information is available at Peer review Information Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Late treatment
is less effective
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