Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population
Sabra L. Klein, … , Arturo Casadevall, Aaron A.R. Tobian
Sabra L. Klein, … , Arturo Casadevall, Aaron A.R. Tobian
Published August 7, 2020
Citation Information: J Clin Invest. 2020;130(11):6141-6150. https://doi.org/10.1172/JCI142004.
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Research Article COVID-19

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 4

Male sex and hospitalization are predictors of overall greater antibody titers in convalescent plasma.

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Male sex and hospitalization are predictors of overall greater antibody ...
(A) Composite scores were computed for each subject on the basis of the quartile of their response across the anti–S protein domain S1-IgG, anti–S-IgG, anti–S-RBD-IgG, and nAb (NT) assays. The distribution of scores among the study population is shown to the right of the heatmap. (B–E) Multiple linear regression analysis was performed on the continuous outcome of score, including parameters for sex, age in decades, hospitalization status, and number of days since collection of the PCR+ nasal swab scaled by 10. For each predictor, the raw data are shown in gray, and the marginal effect plus 95% CI of the given predictor for the average individual in the study is shown in white. P values on top of each panel represent the significance level for the parameter. (F) Summary of the model, where the position of the marker indicates the coefficient value and 95% CI or the expected increase in score for a 1-unit increase in each predictor.