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

Abstract

Multiple randomized, controlled clinical trials have yielded discordant results regarding the efficacy of convalescent plasma in outpatients, with some showing an approximate two-fold reduction in risk and others showing no effect. We quantified binding and neutralizing antibody levels in 492 of the 511 participants from the C3PO trial of a single unit of COVID-19 convalescent plasma (CCP) vs. 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 two-fold higher one hour post-infusion in recipients of CCP compared to saline plus multivitamin, but levels achieved by the native immune system by day 15 were almost ten-fold higher than 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.*The C3PO primary efficacy outcome of disease progression was defined as an emergency department (ED) or urgent care (UC) visit, hospital admission or death without a hospital admission within 15-days from randomization. ¶ The overall population is defined as randomized C3PO patients who had a baseline assay result and at least 1 post-baseline assay result.

Clinical outcomes in hospitalized plasma and platelet transfusion recipients prior to and following widespread blood donor SARS‐CoV‐2 infection and vaccination

“…Again, we found no worsening of outcomes in the study‐eligible transfused population during this period nor among a subgroup of unvaccinated transfusion recipients; the latter notable because some recipients of blood products have expressed concern about the passive transfer of SARS‐CoV‐2 antigens or antibodies 19 . Our findings are also consistent with clinical trial and observational data supporting the safety of CCP and laboratory‐based studies that did not find evidence of an impact of CCP transfusion on the adaptive immune response of recipients 38 …”

“…19 Our findings are also consistent with clinical trial and observational data supporting the safety of CCP and laboratory-based studies that did not find evidence of an impact of CCP transfusion on the adaptive immune response of recipients. 38 We focused on evaluating outcomes among transfusion recipients during study periods with known variation in donor SARS-CoV-2 infection and vaccination. [10][11][12] However, it is worth recognizing that other factors occurring Note: Adjusted odds ratios (aOR) with 95% confidence interval presented for oxygen requirements and thromboses in pre-vaccine and post-vaccine study periods relative to the Pre-COVID period adjusting for demographics and comorbidities presented in Table 1 and number of plasma, platelet, and RBC units.…”

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial

“…However, our findings show that transfusion of CCP, as compared to control plasma, was not associated with differences in the total antibody level immune response in recipients, reassuring for the immunological safety of CCP in humans. The C3PO convalescent plasma study also demonstrated no antibody level difference between CCP and saline infusions(14, 18).…”

Safety of COVID‐19 convalescent plasma: A definitive systematic review and meta‐analysis of randomized controlled trials

“…Finally, there was concern that CCP administration would blunt the immune response to SARS-CoV-2 but recent studies of participants in the C3PO trial showed no evidence that adaptive immune responses were affected. 64 Our systematic review has some limitations. The first is that most RCTs included CCP safety evaluation as secondary outcome, and this aspect could have influenced the accuracy of data recording.…”

“…Although recent studies have provided evidence that CCP with such antibodies was not harmful, 63 our results provide additional reassurance this regard. Finally, there was concern that CCP administration would blunt the immune response to SARS‐CoV‐2 but recent studies of participants in the C3PO trial showed no evidence that adaptive immune responses were affected 64 …”