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COVID-19 convalescent plasma boosts early antibody titer and does not influence the adaptive immune response
John F. McDyer, … , Philip J. Norris, for the SIREN-C3PO Investigators
John F. McDyer, … , Philip J. Norris, for the SIREN-C3PO Investigators
Published March 2, 2023
Citation Information: JCI Insight. 2023;8(8):e167890. https://doi.org/10.1172/jci.insight.167890.
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Research Article COVID-19 Immunology

COVID-19 convalescent plasma boosts early antibody titer and does not influence the adaptive immune response

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Abstract

Multiple randomized, controlled clinical trials have yielded discordant results regarding the efficacy of convalescent plasma in outpatients, with some showing an approximately 2-fold reduction in risk and others showing no effect. We quantified binding and neutralizing antibody levels in 492 of the 511 participants from the Clinical Trial of COVID-19 Convalescent Plasma in Outpatients (C3PO) of a single unit of COVID-19 convalescent plasma (CCP) versus saline infusion. In a subset of 70 participants, peripheral blood mononuclear cells were obtained to define the evolution of B and T cell responses through day 30. Binding and neutralizing antibody responses were approximately 2-fold higher 1 hour after infusion in recipients of CCP compared with saline plus multivitamin, but levels achieved by the native immune system by day 15 were almost 10-fold higher than those seen immediately after CCP administration. Infusion of CCP did not block generation of the host antibody response or skew B or T cell phenotype or maturation. Activated CD4+ and CD8+ T cells were associated with more severe disease outcome. These data show that CCP leads to a measurable boost in anti–SARS-CoV-2 antibodies but that the boost is modest and may not be sufficient to alter disease course.

Authors

John F. McDyer, Mahzad Azimpouran, Valerie L. Durkalski-Mauldin, Robert G. Clevenger, Sharon D. Yeatts, Xutao Deng, William Barsan, Robert Silbergleit, Nahed El Kassar, Iulia Popescu, Dimiter Dimitrov, Wei Li, Emily J. Lyons, Sophia C. Lieber, Mars Stone, Frederick K. Korley, Clifton W. Callaway, Larry J. Dumont, Philip J. Norris, for the SIREN-C3PO Investigators

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Figure 2

Evolution of antibody responses in study participants.

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Evolution of antibody responses in study participants.
(A) Binding antib...
(A) Binding antibody responses were measured using an ELISA from EUROIMMUN, and the natural log of the ratio of the sample OD to a calibrator OD is shown for the saline (black line) versus CCP (orange line) recipients across the 4 sample time points. (B and C) Individual participants’ data are shown in gray lines, with the average for the saline (black) and CCP (orange) recipients plotted for subjects who were seronegative for binding antibodies at BL (B) or seropositive for binding antibodies at BL (C). (D) Neutralizing antibody activity was measured using the Broad Institute assay and reported as the 50% inhibitory dose (ID50). (E and F) Results separated by participants who were seronegative (E) or seropositive (F) at BL for neutralizing antibody activity (titer threshold of 1:40). Error bars represent 95% CI limits for the mean. ****P < 0.0001 for saline versus CCP groups at each time point. P values are based on a 2-tailed t test comparing the differences within each specific visit day, adjusted for multiple comparisons.

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