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

Noriko Iwamoto; Yuki Takamatsu; Yusuke Asai; Kiyoto Tsuchiya; Kouki Matsuda; Yusuke Oshiro; Natsumi Inamura; Mari Terada; Takashi Nemoto; Moto Kimura; Sho Saito; Shinichiro Morioka; Maeda Kenji; Hiroaki Mitsuya; Norio Ohmagari

doi:10.1016/j.heliyon.2024.e24513

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

Heliyon. 2024 Jan 13;10(2):e24513. doi: 10.1016/j.heliyon.2024.e24513. eCollection 2024 Jan 30.

Authors

Noriko Iwamoto¹, Yuki Takamatsu², Yusuke Asai¹, Kiyoto Tsuchiya³, Kouki Matsuda^{2

4}, Yusuke Oshiro⁵, Natsumi Inamura⁵, Mari Terada^{1

6}, Takashi Nemoto⁵, Moto Kimura⁶, Sho Saito¹, Shinichiro Morioka¹, Maeda Kenji^{2

4}, Hiroaki Mitsuya^{2

7

8}, Norio Ohmagari¹

Affiliations

¹ Department of Disease Control Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
² Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan.
³ AIDS Clinical Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
⁴ Division of Antiviral Therapy, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Japan.
⁵ Clinical Laboratory Department, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan.
⁶ Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
⁷ Experimental Retrovirology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁸ Department of Clinical Sciences, Kumamoto University School of Medicine, Kumamoto, Japan.

Abstract

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 in vitro IgG-EC_₅₀ values and S-IgG values.

Methods: We evaluated the neutralizing activity of purified IgG (IgG-EC₅₀), 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-EC₅₀ 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-EC₅₀.

Results: A high correlation was observed between S-IgG and IgG-EC₅₀ with a Spearman's ρ value of -0.748 (95 % confidence interval [CI]: -0.804-0.678). Using an IgG-EC₅₀ of 50 μg/mL and 20 μg/mL as the cut-off values for moderate and high in vitro 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 in vitro virus-neutralizing activity, with a high correlation with IgG-EC₅₀ when the rational cut-off value is carefully determined.

Keywords: COVID-19; Diagnostic tools; Neutralizing antibody; Quantitative anti-SARS-CoV-2-spike-IgG antibody test; SARS-CoV-2.