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. 2023 Aug:165:105518.
doi: 10.1016/j.jcv.2023.105518. Epub 2023 Jun 9.

Performance of commercial SARS-CoV-2 wild-type and Omicron BA.1 antibody assays compared with pseudovirus neutralization tests

E Habermann  1 , L M Frommert  1 , K Ghannam  1 , L Nguyen My  1 , L Gieselmann  2 , P Tober-Lau  3 , J Klotsche  4 , A N Arumahandi de Silva  1 , A Ten Hagen  1 , J Zernicke  1 , F Kurth  3 , L E Sander  3 , F Klein  2 , G R Burmester  1 , R Biesen  1 , F N Albach  5
Affiliations

Performance of commercial SARS-CoV-2 wild-type and Omicron BA.1 antibody assays compared with pseudovirus neutralization tests

E Habermann et al. J Clin Virol. 2023 Aug.

Abstract

Background: Commercially available ELISA-based antibody tests are used to approximate vaccination success against SARS-CoV-2 in at-risk patients, but it is unclear whether they correlate with neutralization of the Omicron variant.

Methods: 269 serum samples of a cohort of 44 non-immunosuppressed participants and 65 MTX-treated rheumatic patients taken before and after COVID-19 booster vaccinations were measured using COVID-19 antibody testing systems with wild-type and Omicron BA.1 antigens developed by three different manufacturers (surrogate virus neutralization test cPass, and binding antibody tests QuantiVac and SeraSpot), as well as with a pseudovirus neutralization test (pVNT). The pVNT was considered the gold standard for determining the presence and level of anti-SARS-CoV-2 antibodies.

Results: All three wild-type ELISAs showed excellent test performance compared with wild-type neutralization in pVNT. However, out of 56 samples without Omicron BA.1 neutralization in pVNT, 71.4% showed positive results in at least one and 28.6% in all three wild-type ELISAs at the manufacturer-defined cut-offs. Omicron ELISAs showed either decreased specificity (57.1% and 55.4% for binding ELISAs) or sensitivity (51.2% in cPass) compared to Omicron neutralization in pVNT. The proportion of any false positive results among all samples decreased from 26.5% before to 3.2% after booster vaccination, however binding antibody test specificities remained below 70%.

Conclusions: We found a poorer test performance of new Omicron antibody test systems compared to wild-type tests in detecting neutralizing antibodies against the corresponding SARS-CoV-2 variants. Decisions for booster vaccination or passive immunization of at-risk patients should not be based solely on antibody test results.

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Conflict of interest statement

Declaration of Competing Interest Euroimmun provided test kits for antibody testing free of charge as part of a research agreement. Otherwise, the authors declare that there are no conflicts of interest.

Figures

Fig 1:
Fig. 1
Wild-type (blue dots) and Omicron (green dots) pVNT results at different time points before and after booster vaccinations. Light blue and green dots indicate results of MTX patients, dark blue and green dots indicate results of NIP. The dotted line marks the lower limit of quantification (LLOQ) of the pVNT (ID50 of 10). ID50s below the LLOQ (ID50=10) were randomly assigned to a value between 4 and 7 to increase visibility of individual results in this graph. MTX, methotrexate; NIP, non-immunosuppressed persons; Om, Omicron; pVNT, Pseudovirus neutralization assay; Wt, wild-type; w, weeks. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig 2:
Fig. 2
Scatter plot and ROC analysis of wild-type and Omicron antibody tests compared with wild-type and Omicron pVNT. A) Wt-ELISAs vs Wt-pVNT B) Wt-ELISAs vs Om-pVNT C) Om-ELISAs vs Om-pVNT. Dotted horizontal and vertical lines mark manufacturer's cut-offs for seropositivity. Om, Omicron BA.1; rS, Spearman's rank correlation coefficient (p<0.001 in all tested correlations); Wt, wild-type; white dots: measurement before first booster; dark dots: measurement after first booster. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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