Correlation of sample-to-cut-off ratio of anti-SARS-CoV-2 IgG antibody chemiluminescent assay with neutralization activity: a prospective multi-centric study in India

Abstract

Background and objectives: There are limited published data on association of results from commercial serological anti-SARS-CoV-2 IgG antibody CLIA (chemiluminescent immunoassay) assays with neutralizing antibodies. This study was undertaken with an objective to correlate sample-to-cut-off (S/Co) ratio of CLIA antibody tests with inhibition activity, which may then serve as a valuable guide for labelling plasma as COVID convalescent plasma (CCP) for therapy and assessing vaccine efficacy.

Materials and methods: A total of 139 donor serum samples who were previously RT-PCR positive and had recovered completely from COVID-19 at least 28 days prior to collection of samples were recruited at three sites. The samples were analysed for S/Co ratio and per cent inhibition activity with VITROS SARS-CoV-2 IgG chemiluminescent assay and GenScript cPass SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT) kit, respectively. Linear regression equation and receiver operating characteristic (ROC) curve were used to check the proposed model of comparing S/Co with per cent inhibition.

Results: The results indicate very good correlation between the S/Co ratio of the chemiluminescent IgG assay and the neutralization activity depicted by per cent inhibition on sVNT assay. S/Co ratio of 4·04 (low-titre) and 8·19 (high-titre) correlated with 30% and 68% inhibition, respectively.

Conclusion: Chemiluminescent SARS-CoV-2 IgG assay can be used as a semi-quantitative test, with a cut-off of >8·19S/Co ratio for selecting donors for convalescent plasma therapy and assessing efficacy of vaccination.

Keywords: anti‐SARS‐CoV‐2 IgG antibodies; convalescent plasma; correlation; immunoassay; neutralization.

Fig. 1

Box and whisker plot of S/Co ratio of chemiluminescence immunoassay (CLIA) SARS‐CoV‐2 IgG antibody assay and percentage inhibition on surrogate virus neutralization test (sVNT) assay.

Fig. 2

Scatter plot and ROC* curves. Figure a and figure b is scatter plot and ROC curve for 30% inhibition on cPass sVNT kit (sensitivity: 94·8%, specificity: 91·3%, CI 95%: 0·955–0·999, AUC**: 0·977). Figure c and figure d is scatter plot and ROC curve for 68% inhibition on cPass sVNT kit (sensitivity: 80·9%, specificity: 90·1%, CI 95%: 0·955–0·999, AUC: 0·953). *ROC receiver operator characteristics; **AUC, area under curve.