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

Habermann, Elisa; Frommert, Leonie Maria; Ghannam, Khetam; My, Ln; Gieselmann, Lutz; Tober‐Lau, Pinkus; Silva, Amanthi Nadira Arumahandi de; Hagen, Alexander ten; Zernicke, Jan; Kurth, Florian; Sander, Leif E.; Klein, Florian; Burmester, G. R.; Biesen, Robert; Albach, Fredrik N.

doi:10.1016/j.jcv.2023.105518

Cited by 3 publications

(1 citation statement)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Commercial assays developed early during the pandemic are based on ancestral/wild-type antigens. Subsequently, there is potential for differential performance in the Omicron-era: in particular, S-and RBD-specific immunoassays have shown significantly reduced performance (112)(113)(114), and decreased comparability of quantitative results (115).…”

Section: Commercial High-throughput Immunoassaysmentioning

confidence: 99%

Clinical and laboratory considerations: Determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19

Holdenrieder,

Ferreira,

Izopet

et al. 2023

Preprint

View full text Add to dashboard Cite

Much of the global population now has some level of adaptive immunity to SARS-CoV-2 induced by exposure to the virus (natural infection), vaccination, or a combination of both (hybrid immunity). Key questions that subsequently arise relate to the duration and the level of protection an individual might expect based on their infection and vaccination history. A multi-component composite correlate of risk (CoR) could inform individuals and stakeholders about protection and aid decision making. This perspective evaluates the various elements that need to be accommodated in the development of an antibody-based composite CoR for reinfection with SARS-CoV-2 or development of severe COVID-19, including variation in exposure dose, transmission route, viral genetic variation, patient factors, and vaccination status. We provide an overview of antibody dynamics to aid exploration of the specifics of SARS-CoV-2 antibody testing. We further discuss anti-SARS-CoV-2 immunoassays, sample matrices, testing formats, frequency of sampling and the optimal time point for such sampling. Whilst the development of a composite CoR is challenging, we provide our recommendations for each of these key areas and highlight areas that require further work to be undertaken.

show abstract

Section: Commercial High-throughput Immunoassaysmentioning

confidence: 99%

Clinical and laboratory considerations: Determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19

Holdenrieder,

Ferreira,

Izopet

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Anti-SARS-CoV-2 serology based on ancestral RBD antigens does not correlate with the presence of neutralizing antibodies against Omicron variants

Dépéry,

Bally,

Amen

et al. 2024

Microbiol Spectr

View full text Add to dashboard Cite

Neutralizing antibody titers and binding antibody levels are considered correlates of protection against severe SARS-CoV-2 infection. The clinical utility of serology should be reevaluated in light of the emergence of escape variants, as commercial antibody-binding assays have not been adapted to the virus’ antigenic evolution. We compared anti-SARS-CoV-2 antibody titers in four quantitative serological tests based on variable ancestral spike antigens (three in-house ELISAs and the prototype VIDAS SARS-CoV-2 IgG QUANT assay) and neutralization assays against the pseudotyped Wuhan, BA.2, BA.4/5, BQ.1.1, and XBB.1.1 viruses in a cohort of 100 patients infected in 2020 or during the Omicron waves. Binding antibody levels correlated well with neutralizing antibody titers for Wuhan, BA.2, and BA.4/5, but the association decreased for BQ.1.1 and XBB.1 (for the VIDAS assay, Spearman’s correlation was 0.82 [95% CI 0.74–0.88] and 0.61 [0.46–0.72] for BA.2 and XBB.1, respectively). In 15% of patients with no neutralizing antibodies against XBB.1, the VIDAS assay still yielded binding antibody levels ranging from 74 to 7,652 binding antibody units/mL. Using an adjusted threshold based on receiver operating characteristic (ROC) curve analysis, the specificity of neutralizing antibody detection increased from 0.15 (95% CI 0.02–0.45) and 0.17 (0.04–0.41) to 0.92 (0.64–1.00) and 0.83 (0.59–0.96) against BQ.1.1 and XBB.1, respectively. Serological tests based on receptor-binding domain antigens from the ancestral virus fail to predict neutralizing activity against the latest circulating Omicron variants. Adapting serological tests may improve their clinical utility in immunocompromised patients. IMPORTANCE Anti-SARS-CoV-2 serology was developed in 2020 in response to the COVID-19 pandemic to diagnose SARS-CoV-2 infection and monitor an individual’s immunity following natural infection or vaccination. Given the relationship between neutralizing antibody titers and protection against severe infection, many studies have evaluated the correlation between serology tests and neutralization assays in the pre-Omicron era. An important potential clinical use of serology, which explores binding antibodies, is estimating an individual’s level of protection against new infection, particularly in immunosuppressed individuals and those at risk of severe COVID. However, in the Omicron era, as new viruses evade the immunity induced by previous infections and vaccination, the correlation between binding antibody levels determined by serological assays developed from ancestral antigens and neutralizing antibody titers against new viruses should be re-examined in order to determine whether these assays should be optimized by adapting antigens to the circulating SARS-CoV-2 strains.

show abstract

Clinical and laboratory considerations: determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19

Holdenrieder,

Dos Santos Ferreira,

Izopet

et al. 2023

Front. Public Health

View full text Add to dashboard Cite

Much of the global population now has some level of adaptive immunity to SARS-CoV-2 induced by exposure to the virus (natural infection), vaccination, or a combination of both (hybrid immunity). Key questions that subsequently arise relate to the duration and the level of protection an individual might expect based on their infection and vaccination history. A multi-component composite correlate of risk (CoR) could inform individuals and stakeholders about protection and aid decision making. This perspective evaluates the various elements that need to be accommodated in the development of an antibody-based composite CoR for reinfection with SARS-CoV-2 or development of severe COVID-19, including variation in exposure dose, transmission route, viral genetic variation, patient factors, and vaccination status. We provide an overview of antibody dynamics to aid exploration of the specifics of SARS-CoV-2 antibody testing. We further discuss anti-SARS-CoV-2 immunoassays, sample matrices, testing formats, frequency of sampling and the optimal time point for such sampling. While the development of a composite CoR is challenging, we provide our recommendations for each of these key areas and highlight areas that require further work to be undertaken.

show abstract

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

Cited by 3 publications

References 13 publications

Clinical and laboratory considerations: Determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19

Clinical and laboratory considerations: Determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19

Anti-SARS-CoV-2 serology based on ancestral RBD antigens does not correlate with the presence of neutralizing antibodies against Omicron variants

Clinical and laboratory considerations: determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19

Contact Info

Product

Resources

About