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Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population.
J Clin Invest. 2020 11 02; 130(11):6141-6150.JCI

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+Show Affiliations

W. Harry Feinstone Department of Molecular Microbiology and Immunology. Department of Biochemistry and Molecular Biology. Department of International Health, and.W. Harry Feinstone Department of Molecular Microbiology and Immunology. Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.W. Harry Feinstone Department of Molecular Microbiology and Immunology.Department of Biochemistry and Molecular Biology.Department of International Health, and.Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.W. Harry Feinstone Department of Molecular Microbiology and Immunology.Advanced Mammalian Biomanufacturing Innovation Center, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.Advanced Mammalian Biomanufacturing Innovation Center, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.Advanced Mammalian Biomanufacturing Innovation Center, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.W. Harry Feinstone Department of Molecular Microbiology and Immunology.Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.W. Harry Feinstone Department of Molecular Microbiology and Immunology.Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

32764200

Citation

Klein, Sabra L., et al. "Sex, Age, and Hospitalization Drive Antibody Responses in a COVID-19 Convalescent Plasma Donor Population." The Journal of Clinical Investigation, vol. 130, no. 11, 2020, pp. 6141-6150.
Klein SL, Pekosz A, Park HS, et al. Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population. J Clin Invest. 2020;130(11):6141-6150.
Klein, S. L., Pekosz, A., Park, H. S., Ursin, R. L., Shapiro, J. R., Benner, S. E., Littlefield, K., Kumar, S., Naik, H. M., Betenbaugh, M. J., Shrestha, R., Wu, A. A., Hughes, R. M., Burgess, I., Caturegli, P., Laeyendecker, O., Quinn, T. C., Sullivan, D., Shoham, S., ... Tobian, A. A. (2020). Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population. The Journal of Clinical Investigation, 130(11), 6141-6150. https://doi.org/10.1172/JCI142004
Klein SL, et al. Sex, Age, and Hospitalization Drive Antibody Responses in a COVID-19 Convalescent Plasma Donor Population. J Clin Invest. 2020 11 2;130(11):6141-6150. PubMed PMID: 32764200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population. AU - Klein,Sabra L, AU - Pekosz,Andrew, AU - Park,Han-Sol, AU - Ursin,Rebecca L, AU - Shapiro,Janna R, AU - Benner,Sarah E, AU - Littlefield,Kirsten, AU - Kumar,Swetha, AU - Naik,Harnish Mukesh, AU - Betenbaugh,Michael J, AU - Shrestha,Ruchee, AU - Wu,Annie A, AU - Hughes,Robert M, AU - Burgess,Imani, AU - Caturegli,Patricio, AU - Laeyendecker,Oliver, AU - Quinn,Thomas C, AU - Sullivan,David, AU - Shoham,Shmuel, AU - Redd,Andrew D, AU - Bloch,Evan M, AU - Casadevall,Arturo, AU - Tobian,Aaron Ar, PY - 2020/07/07/received PY - 2020/08/06/accepted PY - 2020/8/9/pubmed PY - 2020/11/20/medline PY - 2020/8/9/entrez KW - COVID-19 KW - Immunoglobulins SP - 6141 EP - 6150 JF - The Journal of clinical investigation JO - J Clin Invest VL - 130 IS - 11 N2 - 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. SN - 1558-8238 UR - https://www.unboundmedicine.com/medline/citation/32764200/Sex_age_and_hospitalization_drive_antibody_responses_in_a_COVID_19_convalescent_plasma_donor_population_ L2 - https://doi.org/10.1172/JCI142004 DB - PRIME DP - Unbound Medicine ER -