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

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.

SUBMITTER: Gharbharan A

PROVIDER: S-EPMC8160346 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Gharbharan Arvind A Jordans Carlijn C E CCE GeurtsvanKessel Corine C den Hollander Jan G JG Karim Faiz F Mollema Femke P N FPN Stalenhoef-Schukken Janneke E JE Dofferhoff Anthonius A Ludwig Inge I Koster Adrianus A Hassing Robert-Jan RJ Bos Jeannet C JC van Pottelberge Geert R GR Vlasveld Imro N IN Ammerlaan Heidi S M HSM van Leeuwen-Segarceanu Elena M EM Miedema Jelle J van der Eerden Menno M Schrama Thijs J TJ Papageorgiou Grigorios G Te Boekhorst Peter P Swaneveld Francis H FH Mueller Yvonne M YM Schreurs Marco W J MWJ van Kampen Jeroen J A JJA Rockx Barry B Okba Nisreen M A NMA Katsikis Peter D PD Koopmans Marion P G MPG Haagmans Bart L BL Rokx Casper C Rijnders Bart J A BJA

Nature communications 20210527 1

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 ...[more]

PMID: 34045486

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Project description:Currently, neutralizing antibody and vaccine strategies have been developed by targeting the SARS-CoV-2 strain identified during the early phase of the pandemic. Early studies showed that the ability of SARS-CoV-2 RBD or NTD antibodies to elicit infection enhancement in vivo is still controversial. There are growing concerns that the plasma and neutralizing antibodies from convalescent patients or people receiving vaccines mediate ADE of SARS-CoV-2 variants infections in immune cells. Here, we constructed engineered double-mutant variants containing an RBD mutation and D614G in the spike (S) protein and natural epidemic variants to gain insights into the correlation between the mutations in S proteins and the ADE activities and tested whether convalescent plasma and TOP10 neutralizing antibodies in our laboratory mediated the ADE effects of these SARS-CoV-2 variants. We found that one out of 29 convalescent plasma samples caused the ADE effect of pandemic variant B.1.1.7 and that the ADE effect of wild-type SARS-CoV-2 was not detected for any of these plasma samples. Only one antibody, 55A8, from the same batch of convalescent patients mediated the ADE effects of multiple SARS-CoV-2 variants in vitro, including six double-mutant variants and four epidemic variants, suggesting that ADE activities may be closely related to the antibody itself and the SARS-CoV-2 variants' S proteins. Moreover, the ADE activity of 55A8 depended on FcγRII on immune cells, and the introduction of LALA mutations at the Fc end of 55A8 eliminated the ADE effects in vitro, indicating that 55A8LALA may be a clinical drug used to prevent SARS-CoV-2 variants. Altogether, ADE may occur in rare convalescent patients or vaccinees with ADE-active antibodies who are then exposed to a SARS-CoV-2 variant. These data suggested that potential neutralizing antibodies may need to undergo ADE screening tests for SARS-CoV-2 variants, which should aid in the future design of effective antibody-based therapies.

Dataset Information

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

Publications

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

Similar Datasets

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