Characterization of 100 sequential SARS-CoV-2 convalescent plasma donations

Abstract

Background: Transfusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma is a promising treatment for severe coronavirus disease 2019 (COVID-19) cases, with success of the intervention based on neutralizing antibody content. Measurement by serologic correlates without biocontainment needs as well as an understanding of donor characteristics that may allow for targeting of more potent donors would greatly facilitate effective collection.

Study design and methods: One hundred convalescent plasma units were characterized for functionally active SARS-CoV-2 neutralizing antibodies, as well as for SARS-CoV-2 binding antibodies, with the intention to establish a correlation between the functionally more relevant neutralization assay and the more accessible enzyme-linked immunosorbent assay (ELISA). Donor demographics such as COVID-19 severity, age, and sex were correlated with antibody titers.

Results: A mean neutralization titer 50% of 230 (range, <8-1765) was seen for the 100 convalescent plasma units, with highly significant (P < .0001) yet quantitatively limited (R² = 0.2830) correlation with results of the ELISA. Exclusion of units with particularly high titers (>500) from analysis improved correlation (R² = 0.5386). A tendency of higher-titer plasma units from donors with increased disease severity, of advanced age, and of male sex was seen, yet the functional relevance of this difference is questionable.

Conclusion: The ELISA-based correlation to neutralization titer enabled a threshold proposal that could be used to eliminate lower-titer units from the clinical supply for COVID-19 treatment. Disease severity may be associated with the development of higher titers of neutralizing antibodies, although larger case numbers will be needed for additional confirmation.

Keywords: COVID-19; ELISA correlation; convalescent donor selection; severe acute respiratory syndrome coronavirus 2; virus neutralization.

FIGURE 1

Characterization of 100 convalescent plasma donations collected at the Vienna Blood Centre for (A) SARS‐CoV‐2 neutralizing antibody content, reported as log₂ microneutralization titers 50% (X) plotted against the relative frequency (percent) of occurrence. B, NT₅₀ titers were correlated against Euroimmun IgG ELISA signal ratios obtained for the same donations [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

COVID‐19 convalescent plasma donor demographics illustrating (A), correlation of SARS‐CoV‐2 neutralizing antibody titers (NT₅₀) with donor age and (B) difference in NT₅₀ between female and male donors