key: cord-0898319-wgdt5nt1 authors: Lukaszuk, K.; Kiewisz, J.; Rozanska, K.; Podolak, A.; Jakiel, G.; Woclawek-Potocka, I.; Lukaszuk, A.; Rabalski, L. title: Is WHO International Standard for Anti-SARS-CoV-2 Immunoglobulin Clinically Useful? date: 2021-05-02 journal: nan DOI: 10.1101/2021.04.29.21256246 sha: 4852fc5dc60870584f8f986e218d284cafc0ddf5 doc_id: 898319 cord_uid: wgdt5nt1 Background: The introduction of vaccination against SARS-CoV-2 infection needs precise instruments for quality control of vaccination procedure, detection of poor immunological response and estimation of the achieved protection against the disease but also against infection and being infective. Objective: To compare new automated SARS-CoV 2 Ig assay performance characteristics from the automated Elecsys SARS CoV 2 S (Roche) with the new LIAISON SARS-CoV-2 TrimericS IgG (DiaSorin) assay and their compatibility with WHO International Standard for anti-SARS-CoV-2 immunoglobulin. In the context of the mass vaccination programs, we undertook the investigation of clinical utility of the two new automated assays by analyzing results in samples collected at specified time points relative to the vaccination time. Design: Prospective assay evaluation. Patients: Medical staff undergoing vaccination with BioNTech/Pfizer Comirnaty vaccine between January and March 2021 (n = 79) and referred for serum antiSARS-CoV 2 Ig testing prior to vaccination, 21 days after the first dose, and 8, 14 and 30 days after the second dose. Main Outcome Measure(s): Serum antibody levels measured with Roche and DiaSorin assays. Results: Intra-assay imprecision was low with DiaSorin at 3.46%; and Roche at 2.5%. The Passing-Bablok regression equation for all tested samples was y (DiaSorin) = 184.61 + (1.03 x Roche) and the correlation between the assays (r=0.587; p < 0.0001). Conclusions: The novel automated assays exhibit strong concordance in calibration, with assay-specific interpretation required for routine clinical use. These results highlight the need for further work on the international standard of measurement of SARS-CoV 2 Ig especially in era of vaccination. The serological assays can be useful to detect IgG/IgM antibodies, to assess the degree of immunization, to trace the contacts, and to support the decision to readmit people to work or vaccinate them again. However, the values generated by both assays can be markedly different, and assay-specific and personalized interpretation is required. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 62 infection is rapidly changing the epidemic situation in countries undertaking mass vaccination 63 programs. Therefore, it is now important to define and refine vaccination assessment methods 64 to determine the vaccination course and use them to optimize epidemic management protocols. 65 A variety of kits are used for testing the level of antibodies in blood with ELISA methods. immunoglobulin [1, 2] . The intended use of the International Standard is for the calibration and 78 harmonization of serological assays detecting antibodies neutralizing SARS-CoV-2 [3] . The study has been financed by Invicta Research and Development Center. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The ethical approval was received from the Ethics Committee at the Gdansk Regional Medical Manufacturer-reported assay characteristics, measuring ranges, analytic sensitivity, and 109 detection limits are provided in Table 1 . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Laboratory specific: Two assays were used to determine antibody levels: Elecsys Anti-SARS-CoV-2 S (Roche) and (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 2, 2021. ; https://doi.org/10.1101/2021.04.29.21256246 doi: medRxiv preprint 6 in the units specific for each assay (U/ml for Roche and AU/ml for DiaSorin) and were Assay precision and accuracy 148 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The precision and accuracy of assays are shown in (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 2, 2021. Figure 4 shows Passing-Bablok regression 198 (Fig 4 A, C, E) and Bland-Altman plots (Fig 4 B, D, F) . Samples tested 8 (Fig. 4 A, B) and 14 (Fig. 4 C, D) The correlation of results of SARS-CoV-2 Ig levels was higher for samples taken 30 days after 202 the second vaccine dose (r = 0.554, p = 0.0012; Fig. 4 E, F) . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 2, 2021. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 2, 2021. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The prevalence and high mortality rate associated with SARS-CoV-2 has changed the epidemic, Roche kit makes response assessment difficult due to calibration at a relatively low level and 258 technically unfeasible sample dilution above 10x (dilution over 10x leads to unreliable results -unpublished data). The DiaSorin kit has a very wide measurement range and practically every 260 antibody level produced in a vaccinated person falls within the range that can be determined. 261 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. What is surprising, however, is the large variability in antibody levels when assessing the (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 2, 2021. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. In both cases, the companies confirmed that the results for the WHO reference panel samples (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 2, 2021. ; https://doi.org/10.1101/2021.04.29.21256246 doi: medRxiv preprint Establishment of the WHO International Standard 344 and Reference Panel for antiSARS-CoV-2 antibody First WHO International Standard Anti-SARS-CoV-2 Immunoglobulin (Human) Establishment of the WHO International Standard and Reference Panel for Anti-352 SARS-CoV-2 Antibody R: A language and environment for statistical computing. R 355 Foundation for Statistical Computing Welcome to the tidyverse Method Comparison Regression Comparison of Eight Commercial, High-Throughput, Automated or 364 ELISA Assays Detecting SARS-CoV-2 IgG or Total Antibody No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted Robab Breyer Side-by-Side Comparison of Three Fully 375 Akihide R. Interpreting Diagnostic Tests for SARS-CoV-379 No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted