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.
View: Text | PDF
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

×

Figure 1

IgG is the primary isotype produced against SARS–CoV-2 S protein.

Options: View larger image (or click on image) Download as PowerPoint
IgG is the primary isotype produced against SARS–CoV-2 S protein. Conval...
Convalescent plasma samples from patients who recovered from COVID-19 were used to assess antibody isotypes that recognize SARS–CoV-2 antigens. (A) Commercial kits from EUROIMMUN were used to measure total IgG and IgA antibodies against the SARS–CoV-2 S protein domain S1 at an OD of 450 nm (OD450) and were compared with a calibrator to yield AU. (B) The correlation between anti–S1 isotypes is graphed, with the r value noted. Indirect ELISAs were used to measure IgG, IgM, and IgA antibody levels against S protein (C) and IgG, IgM, and IgA against S-RBD (F) and are graphed as AUC values. The heterogeneity of the IgG, IgM, and IgA antibody responses against S protein (D) and S-RBD (G) are shown in 3D scatter plots, with IgA on the x axis, IgM on the y axis, and IgG on the z axis. The correlations between IgG, IgM, and IgA for S protein (E) and S-RBD (H) are included, with r values shown, and are shaded darker for higher correlation values or lighter for lower correlation values. Data indicate the mean ± SEM. n = 126. *P < 0.05, by paired t test.