Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population
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 (...
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| Published in | The Journal of clinical investigation Vol. 130; no. 11; pp. 6141 - 6150 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Society for Clinical Investigation
01.11.2020
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| Subjects | |
| Online Access | Get full text |
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| 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. |
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| AbstractList | 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.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. 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. |
| Audience | Academic |
| Author | Shoham, Shmuel Redd, Andrew D. Shrestha, Ruchee Park, Han-Sol Tobian, Aaron A.R. Pekosz, Andrew Betenbaugh, Michael J. Caturegli, Patricio Casadevall, Arturo Ursin, Rebecca L. Sullivan, David Kumar, Swetha Benner, Sarah E. Burgess, Imani Wu, Annie A. Laeyendecker, Oliver Naik, Harnish Mukesh Littlefield, Kirsten Klein, Sabra L. Shapiro, Janna R. Hughes, Robert M. Bloch, Evan M. Quinn, Thomas C. |
| AuthorAffiliation | 3 Department of International Health, and 6 Advanced Mammalian Biomanufacturing Innovation Center, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA 7 Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA 5 Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA 2 Department of Biochemistry and Molecular Biology 1 W. Harry Feinstone Department of Molecular Microbiology and Immunology 8 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA 4 Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA |
| AuthorAffiliation_xml | – name: 4 Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA – name: 5 Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA – name: 6 Advanced Mammalian Biomanufacturing Innovation Center, Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA – name: 1 W. Harry Feinstone Department of Molecular Microbiology and Immunology – name: 2 Department of Biochemistry and Molecular Biology – name: 3 Department of International Health, and – name: 8 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA – name: 7 Department of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, USA |
| Author_xml | – sequence: 1 givenname: Sabra L. orcidid: 0000-0002-0730-5224 surname: Klein fullname: Klein, Sabra L. – sequence: 2 givenname: Andrew orcidid: 0000-0003-3248-1761 surname: Pekosz fullname: Pekosz, Andrew – sequence: 3 givenname: Han-Sol surname: Park fullname: Park, Han-Sol – sequence: 4 givenname: Rebecca L. orcidid: 0000-0002-3398-331X surname: Ursin fullname: Ursin, Rebecca L. – sequence: 5 givenname: Janna R. surname: Shapiro fullname: Shapiro, Janna R. – sequence: 6 givenname: Sarah E. surname: Benner fullname: Benner, Sarah E. – sequence: 7 givenname: Kirsten orcidid: 0000-0002-6019-0673 surname: Littlefield fullname: Littlefield, Kirsten – sequence: 8 givenname: Swetha surname: Kumar fullname: Kumar, Swetha – sequence: 9 givenname: Harnish Mukesh orcidid: 0000-0002-8303-4219 surname: Naik fullname: Naik, Harnish Mukesh – sequence: 10 givenname: Michael J. surname: Betenbaugh fullname: Betenbaugh, Michael J. – sequence: 11 givenname: Ruchee surname: Shrestha fullname: Shrestha, Ruchee – sequence: 12 givenname: Annie A. surname: Wu fullname: Wu, Annie A. – sequence: 13 givenname: Robert M. surname: Hughes fullname: Hughes, Robert M. – sequence: 14 givenname: Imani surname: Burgess fullname: Burgess, Imani – sequence: 15 givenname: Patricio surname: Caturegli fullname: Caturegli, Patricio – sequence: 16 givenname: Oliver orcidid: 0000-0002-6429-4760 surname: Laeyendecker fullname: Laeyendecker, Oliver – sequence: 17 givenname: Thomas C. orcidid: 0000-0002-0404-1315 surname: Quinn fullname: Quinn, Thomas C. – sequence: 18 givenname: David surname: Sullivan fullname: Sullivan, David – sequence: 19 givenname: Shmuel surname: Shoham fullname: Shoham, Shmuel – sequence: 20 givenname: Andrew D. surname: Redd fullname: Redd, Andrew D. – sequence: 21 givenname: Evan M. orcidid: 0000-0001-8181-9517 surname: Bloch fullname: Bloch, Evan M. – sequence: 22 givenname: Arturo orcidid: 0000-0002-9402-9167 surname: Casadevall fullname: Casadevall, Arturo – sequence: 23 givenname: Aaron A.R. surname: Tobian fullname: Tobian, Aaron A.R. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32764200$$D View this record in MEDLINE/PubMed |
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