Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population.

Klein, Sabra L; Pekosz, Andrew; Park, Han-Sol; Ursin, Rebecca L; Shapiro, Janna R; Benner, Sarah E; Littlefield, Kirsten; Kumar, Swetha; Naik, Harnish Mukesh; Betenbaugh, Michael; Shrestha, Ruchee; Wu, Annie A; Hughes, Robert M; Burgess, Imani; Caturegli, Patrizio; Laeyendecker, Oliver; Quinn, Thomas C; Sullivan, David J; Shoham, Shmuel; Redd, Andrew D; Bloch, Evan M; Casadevall, Arturo; Tobian, Aaron A R

Convalescent plasma is a leading treatment for COVID-19, but there is a paucity of data identifying therapeutic efficacy. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to spike(S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain(S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101(80%) had detectable neutralizing antibody(nAb) titers. Using nAb titers as the reference, the IgG ELISAs confirmed between 95-98% of the nAb positive, but only 20-32% of the nAb negative samples. Male sex, older age, and hospitalization with COVID-19 were associated with increased antibody responses across the serological assays. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age, and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody responses.