Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population
Sabra L. Klein, Andrew Pekosz, Han-Sol Park, Rebecca L. Ursin, Janna R. Shapiro, Sarah E. Benner, Kirsten Littlefield, Swetha Kumar, Harnish Mukesh Naik, Michael J. Betenbaugh, Ruchee Shrestha, Annie A. Wu, Robert M. Hughes, Imani Burgess, Patricio Caturegli, Oliver Laeyendecker, Thomas C. Quinn, David Sullivan, Shmuel Shoham, Andrew D. Redd, Evan M. Bloch, Arturo Casadevall, Aaron A.R. Tobian
Sabra L. Klein, Andrew Pekosz, Han-Sol Park, Rebecca L. Ursin, Janna R. Shapiro, Sarah E. Benner, Kirsten Littlefield, Swetha Kumar, Harnish Mukesh Naik, Michael J. Betenbaugh, Ruchee Shrestha, Annie A. Wu, Robert M. Hughes, Imani Burgess, Patricio Caturegli, Oliver Laeyendecker, Thomas C. Quinn, David Sullivan, Shmuel Shoham, Andrew D. Redd, Evan M. Bloch, Arturo Casadevall, Aaron A.R. Tobian
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Research Article

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

Abstract

Convalescent plasma is a leading treatment for coronavirus disease 2019 (COVID-19), but there is a paucity of data identifying its therapeutic efficacy. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated using a severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2) virus neutralization assay with Vero-E6-TMPRSS2 cells; a commercial IgG and IgA ELISA to detect the spike (S) protein S1 domain (EUROIMMUN); IgA, IgG, and IgM indirect ELISAs to detect the full-length S protein or S receptor–binding domain (S-RBD); and an IgG avidity assay. We used multiple linear regression and predictive models to assess the correlations between antibody responses and demographic and clinical characteristics. IgG titers were greater than either IgM or IgA titers 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 95%–98% of the nAb-positive samples, but 20%–32% of the nAb-negative samples were still IgG ELISA positive. Male sex, older age, and hospitalization for 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.

Authors

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

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Figure 2

nAb titers correlate with IgG antibodies that recognize SARS–CoV-2 S protein.

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nAb titers correlate with IgG antibodies that recognize SARS–CoV-2 S pro...
Convalescent plasma samples from patients recovered from COVID-19 were used to assess functional antibody levels. (A) Microneutralization assays were performed on each plasma sample in 2-fold serial dilutions, with the AUC calculated for all samples with a titer of 20 or higher. (B) Avidity assay used varying amounts of urea to dissociate the anti–S1 spike protein domain IgG/antigen complex from each plasma sample (represented as arbitrary units, AU) to identify the optimal avidity AU ratio (2 M urea) for subsequent analyses. (C) The correlations between nAb AUC values, anti–S1-IgG avidity AU, anti–S1-IgG AU, anti–S-IgG AUC, and anti–S-RBD-IgG AUC are shown, with the r values indicated as well as darker shading for higher correlation values and lighter shading for lower correlation values. (D) For each ELISA assay, the percentage of positive and negative (neg) samples was defined and compared with the nAb AUC (ref), with the negative cutoff values for each assay listed.