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 A.R.
N1 - Funding Information:
We are grateful to all the study participants who donated plasma, the clinical staff, including Sonali Thapa, Liz Martinez, Mary De’Jarnette, Carlos Aguado, Peggy Iraola, and Jackie Lobien, who collected samples, and the technical staff, including Yolanda Eby, Rey Fernandez, Haley Schmidt, Charles Kirby, Ethan Klock, Owen Baker, Jernelle Miller, and Morgan Keruly, who aliquoted and stored samples for this study. We thank Florian Krammer of the Icahn School of Medicine at Mount Sinai for providing protocols, plasmids, and initial stocks of ELISA antigens and Daniel Smith for assistance with the graphical abstract generated in BioRender. We thank the National Institute of Infectious Diseases, Japan, for providing VeroE6TMPRSS2 cells and acknowledge the Centers for Disease Control and Prevention, BEI Resources, NIAID, NIH for SARS-related coronavirus 2, isolate USA-WA1/2020, NR-5228. This work was supported in part by grants from the NIH Specialized Center of Research Excellence (U54AG062333, to SLK, AP, HSP, and JRS); the NIH Center of Excellence in Influenza Research and Surveillance (HHSN272201400007C, to AP, KL, SLK, and RLU); the NIH Molecular and Cellular Basis of Infectious Diseases program (T32A1007417, to RLU); the NIAID (AI052733 and AI15207, to AC, and R01AI120938, R01AI120938S1, and R01AI128779, to AART); the Division of Intramural Research, NIAID (to OL and TQ); the National Heart, Lung and Blood Institute (NHLBI) (1K23HL151826-01, to EBM, and R01HL059842, to AC); Bloomberg Philanthropies (to AC); and the US Department of Defense (W911QY2090012, to AC and DS).
Funding Information:
We are grateful to all the study participants who donated plasma, the clinical staff, including Sonali Thapa, Liz Martinez, Mary De?Jarnette, Carlos Aguado, Peggy Iraola, and Jackie Lobien, who collected samples, and the technical staff, including Yolanda Eby, Rey Fernandez, Haley Schmidt, Charles Kirby, Ethan Klock, Owen Baker, Jernelle Miller, and Morgan Keruly, who aliquoted and stored samples for this study. We thank Florian Krammer of the Icahn School of Medicine at Mount Sinai for providing protocols, plasmids, and initial stocks of ELISA antigens and Daniel Smith for assistance with the graphical abstract generated in BioRender. We thank the National Institute of Infectious Diseases, Japan, for providing VeroE6TMPRSS2 cells and acknowledge the Centers for Disease Control and Prevention, BEI Resources, NIAID, NIH for SARS-related coronavirus 2, isolate USAWA1/2020, NR-5228. This work was supported in part by grants from the NIH Specialized Center of Research Excellence (U54AG062333, to SLK, AP, HSP, and JRS); the NIH Center of Excellence in Influenza Research and Surveillance (HHSN272201400007C, to AP, KL, SLK, and RLU); the NIH Molecular and Cellular Basis of Infectious Diseases program (T32A1007417, to RLU); the NIAID (AI052733 and AI15207, to AC, and R01AI120938, R01AI120938S1, and R01AI128779, to AART); the Division of Intramural Research, NIAID (to OL and TQ); the National Heart, Lung and Blood Institute (NHLBI) (1K23HL151826-01, to EBM, and R01HL059842, to AC); Bloomberg Philanthropies (to AC); and the US Department of Defense (W911QY2090012, to AC and DS).
Publisher Copyright:
Copyright: © 2020, American Society for Clinical Investigation.
PY - 2020/11/2
Y1 - 2020/11/2
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.
AB - 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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U2 - 10.1172/JCI142004
DO - 10.1172/JCI142004
M3 - Article
C2 - 32764200
AN - SCOPUS:85091018297
SN - 0021-9738
VL - 130
SP - 6141
EP - 6150
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 11
ER -