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

Clin Chem Lab Med. 2021 Apr 9;59(8):1453-1462. doi: 10.1515/cclm-2021-0214. Print 2021 Jul 27.

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.

Keywords: COVID-19; SARS-CoV-2; neutralization assay; sensitivity; serology; specificity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • COVID-19 / diagnosis*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Male
  • Middle Aged
  • Neutralization Tests*
  • Protein Subunits / immunology
  • Reagent Kits, Diagnostic
  • SARS-CoV-2 / isolation & purification
  • SARS-CoV-2 / metabolism*
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / immunology*
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Protein Subunits
  • Reagent Kits, Diagnostic
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2