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. 2023 Jun:116:1-6.
doi: 10.1016/j.clinbiochem.2023.02.010. Epub 2023 Feb 26.

Evaluation and comparison of four quantitative SARS-CoV-2 serological assays in COVID-19 patients and immunized healthy individuals, cancer patients, and patients with immunosuppressive therapy

Agnes Chan  1 , Jorge Martinez-Cajas  2 , Paul M Yip  3 , Vathany Kulasingam  4 , Jocelyn Garland  5 , David Holland  5 , M Khaled Shamseddin  5 , Yanping Gong  6
Affiliations

Evaluation and comparison of four quantitative SARS-CoV-2 serological assays in COVID-19 patients and immunized healthy individuals, cancer patients, and patients with immunosuppressive therapy

Agnes Chan et al. Clin Biochem. 2023 Jun.

Abstract

Background: Semi-quantitative and quantitative immunoassays are the most commonly used methodology to evaluate immunity post immunization.

Objectives: To compare four quantitative SARS-CoV-2 serological assays in COVID-19 patients and immunized healthy individuals, cancer patients, and patients with immunosuppressive therapy.

Study design: 210 serological samples from COVID-19 infection and vaccination cohorts were used to create a serological sample repository. Serological methods from four manufacturers, namely Euroimmun, Roche, Abbott, and DiaSorin, were evaluated for quantitative, semi-quantitative, and qualitative antibody measurements. All four methods measure IgG antibodies against the SARS-CoV-2 spike receptor-binding domain and report the results in Binding Antibody Unit/mL (BAU/mL). A Total Error Allowable (TEa) of ±25% was chosen as the criteria to determine whether two methods are clinically equivalent quantitatively. Semi-quantitative results (titers) were derived using numeric antibody concentration divided by the cut-off value for each method.

Results: All paired quantitative comparisons demonstrated unacceptable performance. With ±25% as TEa, the best agreement was 74 (35.2% out of 210 samples) between Euroimmun and DiaSorin, whereas the lowest agreement was 11 (5.2% out of 210 samples) between Euroimmun and Roche. Antibody titers amongst all four methods were significantly different (p < 0.001). The highest titer difference from the same sample is between Roche and DiaSorin with a 1392-fold difference. On qualitative comparison, none of the paired comparison showed acceptable comparison (p < 0.001).

Conclusions: Poor correlation exists between four evaluated assays, quantitatively, semi-quantitatively, and qualitatively. Further harmonization of assays is required to achieve comparable measurements.

Keywords: Comparability; SARS-CoV-2 vaccination; Serological assays; Standardization.

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Conflict of interest statement

Declaration of Competing Interest The study was funded by the PSI foundation: 2020–1972, and Southeastern Ontario Academic Medical Organization Innovation Fund 2021. The study received in-kind reagent support and limited financial support from EUROIMMUN AG, Abbott, Roche, and DiaSorin.

Figures

Fig. 1
Fig. 1
Pairwise comparisons of quantitative serological testing.
Fig. 2
Fig. 2
Pairwise comparison of semi-quantitative serological testing agreement.
See this image and copyright information in PMC

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