TY - JOUR
T1 - Assessment of serological assays for identifying high titer convalescent plasma
AU - Farnsworth, Christopher W.
AU - Case, James B.
AU - Hock, Karl
AU - Chen, Rita E.
AU - O'Halloran, Jane A.
AU - Presti, Rachel
AU - Goss, Charles W.
AU - Rauseo, Adriana M.
AU - Ellebedy, Ali
AU - Theel, Elitza S.
AU - Diamond, Michael S.
AU - Henderson, Jeffrey P.
N1 - Funding Information:
This study utilized samples obtained from the Washington University School of Medicine's COVID‐19 biorepository, which is supported by: the Barnes‐Jewish Hospital Foundation; the Siteman Cancer Center grant P30 CA091842 from the National Cancer Institute of the National Institutes of Health; and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences of the National Institutes of Health. Jeffrey P. Henderson acknowledges support from National Institute of Diabetes and Digestive and Kidney Diseases grant RO1DK111930 and the Longer Life Foundation. The content is solely the responsibility of the authors and does not necessarily represent the view of the NIH. Specimen analysis was funded by the Washington University Department of Pathology and Immunology and the Mayo Clinic. No industry sponsors were involved with the collection, analysis, and presentation of data, drafting of the manuscript, or the decision to publish.
Publisher Copyright:
© 2021 AABB
PY - 2021/9
Y1 - 2021/9
N2 - Background: The COVID-19 pandemic has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose–response data using the Ortho VITROS IgG assay. The proliferation of severe acute respiratory syndrome coronavirus 2 serological assays and non-uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between multiple serological assays. Methods: We compared the Ortho, Abbott, Roche, an anti-spike (S) ELISA, and a virus neutralization assay. Relationships relative to FDA-approved cutoffs under the CCP emergency use authorization were identified in convalescent plasma from a cohort of 79 donors from April 2020. Results: Relative to the neutralization assay, the spearman r value of the Ortho Clinical, Abbott, Roche, anti-S ELISA assays was 0.65, 0.59, 0.45, and 0.76, respectively. The best correlative index for establishing high-titer units was 3.87 signal-to-cutoff (S/C) for the Abbott, 13.82 cutoff index for the Roche, 1:1412 for the anti-S ELISA, 1:219 by the neutralization assay, and 15.9 S/C by the Ortho Clinical assay. The overall agreement using derived cutoffs compared to a neutralizing titer of 1:250 was 78.5% for Abbott, 74.7% for Roche, 83.5% for the anti-S ELISA, and 78.5% for Ortho Clinical. DISCUSSION: Assays based on antibodies against the nucleoprotein were positively associated with neutralizing titers and the Ortho assay, although their ability to distinguish FDA high-titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID-19 pandemic.
AB - Background: The COVID-19 pandemic has been accompanied by the largest mobilization of therapeutic convalescent plasma (CCP) in over a century. Initial identification of high titer units was based on dose–response data using the Ortho VITROS IgG assay. The proliferation of severe acute respiratory syndrome coronavirus 2 serological assays and non-uniform application has led to uncertainty about their interrelationships. The purpose of this study was to establish correlations and analogous cutoffs between multiple serological assays. Methods: We compared the Ortho, Abbott, Roche, an anti-spike (S) ELISA, and a virus neutralization assay. Relationships relative to FDA-approved cutoffs under the CCP emergency use authorization were identified in convalescent plasma from a cohort of 79 donors from April 2020. Results: Relative to the neutralization assay, the spearman r value of the Ortho Clinical, Abbott, Roche, anti-S ELISA assays was 0.65, 0.59, 0.45, and 0.76, respectively. The best correlative index for establishing high-titer units was 3.87 signal-to-cutoff (S/C) for the Abbott, 13.82 cutoff index for the Roche, 1:1412 for the anti-S ELISA, 1:219 by the neutralization assay, and 15.9 S/C by the Ortho Clinical assay. The overall agreement using derived cutoffs compared to a neutralizing titer of 1:250 was 78.5% for Abbott, 74.7% for Roche, 83.5% for the anti-S ELISA, and 78.5% for Ortho Clinical. DISCUSSION: Assays based on antibodies against the nucleoprotein were positively associated with neutralizing titers and the Ortho assay, although their ability to distinguish FDA high-titer specimens was imperfect. The resulting relationships help reconcile results from the large body of serological data generated during the COVID-19 pandemic.
KW - COVID-19
KW - SARS-CoV-2
KW - convalescent plasma
KW - serology
UR - http://www.scopus.com/inward/record.url?scp=85109090437&partnerID=8YFLogxK
U2 - 10.1111/trf.16580
DO - 10.1111/trf.16580
M3 - Article
C2 - 34216156
AN - SCOPUS:85109090437
SN - 0041-1132
VL - 61
SP - 2658
EP - 2667
JO - Transfusion
JF - Transfusion
IS - 9
ER -