Can commercial automated immunoassays be utilized to predict neutralizing antibodies after SARS-CoV-2 infection? A comparative study between three different assays

Ahmed Ismail¹, Farah M. Shurrab², Hadeel T. Al-Jighefee^2,3, Duaa W. Al-Sadeq^2,4, Hamda Qotba^5,6, Ibrahim Abdu Al-Shaar¹, Hadi. M. Yassine^2,3, Laith J. Abu-Raddad^7,8,9, Gheyath K. Nasrallah^2,3,*

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¹ Laboratory Section, Medical Commission Department, Ministry of Public Health, 42 Doha, Qatar

² Biomedical Research Center, Qatar University, 2713 Doha, Qatar

³ Department of Biomedical Science, College of Health Sciences, Member of QU Health, Qatar University, 2713 Doha, Qatar

⁴ College of Medicine, Member of QU Health, Qatar University, 2713 Doha, Qatar

⁵ Department of Clinical Research, Primary Health Care Centers, 26555 Doha, Qatar

⁶ Department of Pathology, Sidra Medicine, 26999 Doha, Qatar

⁷ Infectious Disease Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation—Education City, 24144 Doha, Qatar

⁸ World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine—Qatar, Cornell University, Qatar Foundation—Education City, 24144 Doha, Qatar

⁹ Department of Healthcare Policy and Research, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA

^*Correspondence: gheyath.nasrallah@qu.edu.qa (Gheyath K. Nasrallah)

Front. Biosci. (Landmark Ed) 2021, 26(7), 198–206; https://doi.org/10.52586/4934

Submitted: 19 April 2021 | Revised: 22 May 2021 | Accepted: 4 June 2021 | Published: 30 July 2021

This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Abstract

Background: High-throughput assays that can infer neutralizing activity against SARS-CoV-2 are of great importance for assessing the immunity induced by natural infection and COVID-19 vaccines. We aimed to evaluate the performance and degree of correlation of three fully automated anti-SARS-CoV-2 immunoassays with neutralization activity using a surrogate virus-neutralizing test (sVNT) from GenScript, targeting the receptor-binding domain. Methods: 110 sera collected from PCR-confirmed asymptomatic COVID-19 individuals were tested for neutralizing antibodies (nAbs) using the sVNT. Positive samples were tested on three automated immunoassays targeting different viral antigens: Mindray CL-900i®, Abbott Architect, and Ortho VITROS®. The diagnostic sensitivity, specificity, agreement, and correlation with the sVNT were assessed. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal thresholds for predicting the presence of neutralizing activity by each assay. Results: All three assays showed 100% specificities. The highest sensitivity was 99.0%, demonstrated by VITROS®, followed by 94.3%, for CL-900i®, and 81.0%, for Architect. Both VITROS® and CL-900i® had the strongest correlation with the sVNT ( $\rho{}$ = 0.718 and $\rho{}$ = 0.712, respectively), while Architect showed a moderate correlation ( $\rho{}$ = 0.618). ROC curve analysis indicated that the manufacturer’s recommended cutoff values are adequate for predicting the presence of nAbs and providing a strong correlation with the sVNT. Conclusion: VITROS® and CL-900i® serological assays, which detect antibodies against SARS-CoV-2 spike protein, could serve as reliable assays to predict neutralization activity after infection or vaccination.

Keywords

SARS-CoV-2

COVID-19

Serology

Automated immunoassay

CLIA

Neutralizing antibodies

Surrogate virus neutralization test (sVNT)

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Fig. 1.

Correlation and linear regression analysis between each SARS-CoV-2 immunoassay ratio results and the surrogate virus neutralization test (sVNT) percent inhibition in asymptomatic COVID-19 individuals (n = 105). Spearman’s correlation coefficient ( $\rho{}$ ), r ${}^{2}$ , and p-value are shown for each model. Rho ( $\rho{}$ ) is shown with 95% confidence interval (95% CI), a correlation value of $<$ 0.3 is negligible, 0.3–0.5 is weak, 0.5–0.7 is moderate, 0.7–0.9 is strong and $>$ 0.9 is very strong [34]. The dashed red line corresponds to the cutoff value of each assay (CL-900i® $\geq$ 10.0, Architect $\geq$ 1.4, VITROS® $\geq$ 1.0). The significance level was set at 0.05. COI, cutoff index; S/C, signal/cutoff.

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Front. Biosci. (Landmark Ed) Print ISSN 2768-6701 Electronic ISSN 2768-6698