High diagnostic accuracy of quantitative SARS-CoV-2 spike-binding-IgG assay and correlation with viral neutralizing activity.

Background: Antibody testing can easily evaluate the clinical status of patients, aid in the diagnosis of multisystem inflammatory syndrome, and monitor the immunity level in the population. However, the applicability of serological tests in detecting antibodies against the severe acute respiratory syndrome 2 (SARS-CoV-2) spike-binding protein remains limited. This study aimed to quantify both serum-derived neutralizing immunoglobulin-G (IgG) antibody activity and the amount of anti-SARS-CoV-2 Spike-IgG (S-IgG) in convalescent sera/plasmas and evaluate the direct correlation between the IgG-EC values and S-IgG values.

Methods: We evaluated the neutralizing activity of purified IgG (IgG-EC), quantified S-IgG in the serum/plasma of consecutive COVID-19 convalescent individuals using a cell-based virus-neutralizing assay, and determined the correlation between IgG-EC and S-IgG. In addition, we evaluated rational cut-off values using the receiver operating characteristic (ROC) curve and calculated the sensitivity and specificity of the quantitative S-IgG assay for moderate and high IgG-EC.

Results: A high correlation was observed between S-IgG and IgG-EC with a Spearman's ρ value of -0.748 (95 % confidence interval [CI]: -0.804-0.678). Using an IgG-EC of 50 μg/mL and 20 μg/mL as the cut-off values for moderate and high neutralizing activity, respectively, the Youden's index values of 287.5 binding antibody units (BAU)/mL and 454.1 BAU/mL determined from the ROC curve showed the highest diagnostic accuracy, with Kappa values of 0.884 (95 % CI: 0.823-0.946) and 0.920 (95 % CI: 0.681-0.979), respectively.

Conclusions: Quantitative S-IgG tests are a useful and convenient tool for estimating virus-neutralizing activity, with a high correlation with IgG-EC when the rational cut-off value is carefully determined.