AUTHOR=Windsor William Jonathan , Roell Yannik , Tucker Heidi , Cheng Chi-An , Suliman Sara , Peek Laura J. , Pestano Gary A. , Lee William T. , Zeichhardt Heinz , Lamb Molly M. , Kammel Martin , Wang Hui , Kedl Ross , Rester Cody , Morrison Thomas E. , Davenport Bennet J. , Carson Kyle , Yates Jennifer , Howard Kelly , Kulas Karen , Walt David R. , Dafni Aner , Taylor Daniel , Chu May 

TITLE=Harmonization of Multiple SARS-CoV-2 Reference Materials Using the WHO IS (NIBSC 20/136): Results and Implications

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.893801

DOI=10.3389/fmicb.2022.893801

ISSN=1664-302X

ABSTRACT=Background: There is an urgent need for harmonization between SARS-CoV-2 serology platforms and assays prior to defining appropriate correlates of protection and as well inform the development of new rapid diagnostic tests that can be used for sero-surveillance as new variants of concern (VOC) emerge. We compared multiple SARS-CoV-2 serology reference materials to the WHO IS to determine their utility as secondary standards, using an international network of laboratories with high-throughput quantitative serology assays. This enabled the comparison of quantitative results between multiple serology platforms.  Methods: Between April and December of 2020, thirteen well-characterized and validated SARS-CoV-2 serology reference materials were recruited from six different providers to qualify as secondary standards to the WHO International Standard. All samples were tested in parallel with NIBSC 20/136 and parallel line assays were used to compute the relevant potency and binding antibody units. Results: All samples saw varying levels of concordance between diagnostic methods at specific antigen-antibody combinations. Seven of the 12 candidate materials had high concordance for the Spike-IgG analyte (%CV between 5% and 44%). Conclusions: Despite some concordance between laboratories, qualification of secondary materials to a WHO IS using arbitrary IU or BAU/mL does not provide any benefit to the reference materials overall, due to the lack of consistent agreeable IU or BAU/mL conversions between labs. Secondary standards should be qualified to well-characterized reference materials, such as the WHO IS, using serology assays that are similar to the ones used for the original characterization of the WHO IS.