Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern

Abstract

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. COVID-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The Food and Drug Administration currently allows outpatient CCP for the immunosuppressed. Viral-specific antibody levels in CCP can range 10- to 100-fold between donors, unlike the uniform viral-specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-δ/pre-ο donor units obtained before March 2021, 20 post-δ COVID-19/postvaccination units, and 1 pre-δ/pre-ο hyperimmunoglobulin preparation for variant-specific virus (vaccine-related isolate [WA-1], δ, and ο) neutralization correlated to Euroimmun S1 immunoglobulin G antibody levels. We observed a two- to fourfold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to δ or ο, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-δ COVID-19/postvaccination units and the hyperimmunoglobulin effectively neutralized all 3 variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.

Graphical abstract

Figure 1.

Reduction in virus neutralization sorted by plasma type as well as an increase by Euroimmun antibody levels. (A) WA-1, δ, and ο virus microneutralization sorted by the 108 CCP units, post-δ COVID-19/post vaccination, and hyperimmunoglobin. IU/mL geomeans are shown above x-axis. (B) Antibody levels over 3.5 Euroimmun AU show 85% microneutralization with WA-1 and δ, whereas ο neutralization requires Euroimmun AU over 10 for 85% of the 108 CCP donors. Post-δ COVID-19/postvaccination retains 100% virus neutralization for the 3 variants. Virus neutralization is any positive IU/mL over 1. (C) Range of Euroimmun antibody levels sorted by prevaccination 2020 donor collections and early January to March 2021 for the large number of clinical trial donors and the 108 remnant donors. Geomeans near x-axis and number above 10 AU in red above values. More than 10% of units have Euroimmun AU over 10 except for the 2020 remnant units. Three of the 12 2021 108 donors were vaccinated along with documented COVID-19. The vaccine status of the other 9 was not recorded at time of donation. The P values were Tukey’s multiple comparisons of 1-way ANOVA. ****P < .0001; ***P < .001; **P < .01. AU, arbitrary units.

Figure 2.

Sorting higher Euroimmun categories indicates virus neutralization to WA-1, δ, and ο. WA-1 (A), δ (B), and ο (C) virus microneutralization measured in CCP, post-δ COVID-19/postvaccination, and hyperimmune globulin (HIG) sorted for viral-specific antibody levels by Euroimmun AU at 1:101 dilution. IU/mL geometric means are shown above x-axis. The ratio of donor plasma neutralizations to total tested is shown below x-axis (neutralization number/total number).The P values were Tukey’s multiple comparisons of 1-way ANOVA. ****P < .0001; ***P < .001; **P < .01; *P < .05.