Clinical validation of the quantitative Siemens SARS-CoV-2 spike IgG assay (sCOVG) reveals improved sensitivity and a good correlation with virus neutralization titers

Abstract

Objectives: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections cause Coronavirus Disease 2019 (COVID-19) and induce a specific antibody response. Serological assays detecting IgG against the receptor binding domain (RBD) of the spike (S) protein are useful to monitor the immune response after infection or vaccination. The objective of our study was to evaluate the clinical performance of the Siemens SARS-CoV-2 IgG (sCOVG) assay. Methods: Sensitivity and specificity of the Siemens sCOVG test were evaluated on 178 patients with SARS-CoV-2-infection and 160 pre-pandemic samples in comparison with its predecessor test COV2G. Furthermore, correlation with virus neutralization titers was investigated on 134 samples of convalescent COVID-19 patients. Results: Specificity of the sCOVG test was 99.4% and sensitivity was 90.5% (COV2G assay 78.7%; p<0.0001). S1-RBD antibody levels showed a good correlation with virus neutralization titers (r=0.843; p<0.0001) and an overall qualitative agreement of 98.5%. Finally, median S1-RBD IgG levels increase with age and were significantly higher in hospitalized COVID-19 patients (median levels general ward: 25.7 U/ml; intensive care: 59.5 U/ml) than in outpatients (3.8 U/ml; p<0.0001). Conclusions: Performance characteristics of the sCOVG assay have been improved compared to the predecessor test COV2G. Quantitative SARS-CoV-2 S1-RBD IgG levels could be used as a surrogate for virus neutralization capacity. Further harmonization of antibody quantification might assist to monitor the humoral immune response after COVID-19 disease or vaccination.

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection

“…Moreover, anti-RBD and anti-Spike binding assays were equivalent to NA in predicting vaccine efficacy for predicting symptomatic infection [26]. An excellent correlation of anti-RBD and NA was observed in vaccination trials [27][28][29][30] or other studies [6,7,9].…”

“…However, measuring neutralizing antibodies on a large scale is challenging. The development of binding assays directed against the spike protein of SARS-CoV-2 showed excellent correlation with neutralizing antibodies [ 6 , 7 , 8 , 9 ] and provides an opportunity to assess the immunogenicity of SARS-CoV-2 vaccines over time on a large scale. The assessment of vaccine immunogenicity to predict and monitor vaccine effectiveness is important in groups of individuals not included in clinical trials, such as patients with immunocompromising conditions [ 10 ].…”

Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment

“…Moreover, we performed quantitative detection of IgG antibody levels to SARS-CoV-2 S1 antigen using the Siemens SARS-CoV-2 spike IgG assay (sCOVG) as described before. 18 Individual neutralization capacity at 28 days post-booster was assessed using an i n vitro SARS-CoV-2 neutralization test towards the Wuhan (wild type) strain (see Supplementary Appendix).…”

Evaluation of commercial anti-SARS-CoV-2 antibody assays and comparison of standardized titers in vaccinated healthcare workers

“…A limitation of this study is that the specificity analysis was limited to a small group of patients with auto-immune diseases or mycoplasma infection. However, assay specificity analyses have been performed by manufacturers and independent groups (2,(4)(5)(6) showing specificity ≥ 99% for all the quantitative assays. In addition, not all commercial quantitative anti-SARS-CoV-2 Ab assays were evaluated limiting the scope of the conclusions.…”

“…First, binding Ab assays should be quantitative; second, titers should be consistent between different assays; third, binding Ab titers should correlate with neutralizing Ab titers; fourth, the minimum binding Ab titer associated with virus neutralization must be found; and fifth, the association between neutralizing Ab and vaccine protection must be demonstrated. It can be considered that the first and fifth conditions have been met given that commercial tests for the quantitative detection of binding Ab have been developed (2)(3)(4)(5)(6)(7), and that the role of neutralizing Ab in the infection protection have been demonstrated in animals and humans (8)(9)(10)(11); this is not the case for the other conditions. In particular, the second point is of importance for widespread evaluation of vaccines, but until now Ab titers were often expressed as an index or unit with regard to an internal standard that differs between manufacturers.…”