Is WHO International Standard for Anti-SARS-CoV-2 Immunoglobulin Clinically Useful?

Abstract

BackgroundThe 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.ObjectiveTo 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.DesignProspective assay evaluation.PatientsMedical 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.ResultsIntra-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).ConclusionsThe 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.

Third dose of anti-SARS-CoV-2 vaccine for patients with cancer: Should humoral responses be monitored? A position article

“…Such studies are not always able to establish reliable cutoffs, which could be applied to clarify which SARS-Cov-2 Abs levels would support re-vaccination of former infected or vaccinated people, owing to waning immunity. A surprising issue is that even though the sensitivity and specificity of various tests are excellent ( 72 ), the conversion of units from AU/ml to BAU/mL is not at all linear, as reported by others ( 12 , 73 , 74 , 75 ). Kim et al nicely illustrated that a factor 4.5 should be applied to convert Roche Elecsys anti-S Abs titers to Abbott IgG II ( 75 ).…”

Validity of self-testing at home with rapid SARS-CoV-2 antibody detection by lateral flow immunoassay

“…WHO international standard units are BAU ml −1 for anti-spike IgG to allow comparison across studies and platforms (20). The conversion factor for U ml −1 to BAU ml −1 for the Roche Elecsys® Anti-SARS-CoV-2 assay: (19) In addition, we selected 250 serum samples at random for assessment on a live virus neutralisation assay. Serum samples were heat-inactivated and a 2-fold dilution series was performed in 96-well plates.…”

“…The threshold value for antibody positivity for the Roche assay is 0.8 U ml -1 based on manufacturer instructions (18). The lower limit of quantification is 0.4 U ml -1 (19). Measurements below this value were truncated at 0.4 U ml -1 .…”

Changes in spike protein antibody titer over 90 days after the second dose of SARS-CoV-2 vaccine in Japanese dialysis patients

“…1) Antibody titers after the second dose 2) Factors affecting anti-spike protein antibody titers, and contributing to anti-spike protein antibody titers > 137 U/mL at 90 days after the second dose (Chloe's report indicated that the protection was 89.3% with antibody titers > 141BAU and 12.4% with antibody titers of 13 to 141BAU [16]. This antibody titer of 141 BAU corresponding to 89.3% protection was converted to 141*0.972BAU≒137 U/mL using the conversion formula based on the report by Krzysztof et al [17], which was assumed as a measure related to breakthrough infection. An analysis was performed based on whether this level was exceeded.…”

“…In contrast, higher antibody titers than necessary are not required if antibody titers associated with breakthrough infection are maintained. Thus, the value corresponding to 89.3% protection as reported by Chloe [16] was converted to the antibody titer in this study [17], and an antibody titer of 137U/mL (assumed breakthrough level) was assumed as a measure related to breakthrough infection. Factors associated with antibody titers exceeding this level at 90 days were analyzed.…”