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

• Published in: The Journal of clinical investigation Vol. 130; no. 11; pp. 6141 - 6150
• Main Authors: 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 J., Shrestha, Ruchee, Wu, Annie A., Hughes, Robert M., Burgess, Imani, Caturegli, Patricio, Laeyendecker, Oliver, Quinn, Thomas C., Sullivan, David, Shoham, Shmuel, Redd, Andrew D., Bloch, Evan M., Casadevall, Arturo, Tobian, Aaron A.R.
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.11.2020
• Subjects: Adult; Age; Age Factors; Aged; Animals; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibody Formation; Antibody response; Antigen-antibody reactions; Antiviral drugs; Avidity; Betacoronavirus - immunology; Betacoronavirus - metabolism; Biomedical research; Blood Donors; Care and treatment; Chlorocebus aethiops; Convalescence; Convalescent plasma therapy; Coronaviridae; Coronavirus Infections - blood; Coronavirus Infections - immunology; Coronavirus Infections - therapy; Coronaviruses; COVID-19; Demographic aspects; Development and progression; Disease age factors; Enzyme-linked immunosorbent assay; Female; Hospital patients; Hospitalization; Humans; Immune response (humoral); Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic research; Infections; Male; Males; Middle Aged; Pandemics; Patient outcomes; Plasma; Pneumonia, Viral - blood; Pneumonia, Viral - immunology; Pneumonia, Viral - therapy; Prediction models; Proteins; Regression analysis; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Sex Factors; Vero Cells; Viral infections; United States; China; COVID-19; Immunoglobulins
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI142004

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.