Biochemical rationale for transfusion of high titre COVID-19 convalescent plasma

We aimed to model binding of donor antibodies to virus that infects COVID-19 patients following transfusion of convalescent plasma (CCP). An immunosorbent assay was developed to determine apparent affinity (K_{d, app}). Antibody binding to virus was modelled using antibody concentration and estimations of viral load. Assay and model were validated using reference antibodies and clinical data of monoclonal antibody therapy. A single K_{d, app} or two resolvable K_{d, app} were found for IgG in 11% or 89% of CCP donations, respectively. For IgA this was 50%-50%. Median IgG K_{d, app} was 0.8nM and 3.6nM for IgA, ranging from 0.1-14.7nM and 0.2-156.0nM respectively. The median concentration of IgG was 44.0nM (range 8.4-269.0nM) and significantly higher than IgA at 2.0nM (range 0.4-11.4nM). The model suggested that a double CCP transfusion (i.e. 500 mL) allows for > 80% binding of antibody to virus provided K_{d, app} was < 1nM and concentration > 150nM. In our cohort from the pre-vaccination era, 4% of donations fulfilled these criteria. Low and mid-range viral loads are found early post exposure, suggesting that convalescent plasma will be most effective then. This study provides a biochemical rationale for selecting high affinity and high antibody concentration CCP transfused early in the disease course.