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
Affiliations
Noriko Iwamoto
Department of Disease Control Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan; Corresponding author. 1-21-1 Toyama, Shinjuku, Tokyo, 162-8655, Japan.
Yuki Takamatsu
Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
Yusuke Asai
Department of Disease Control Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
Kiyoto Tsuchiya
AIDS Clinical Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
Kouki Matsuda
Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan; Division of Antiviral Therapy, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Japan
Yusuke Oshiro
Clinical Laboratory Department, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
Natsumi Inamura
Clinical Laboratory Department, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
Mari Terada
Department of Disease Control Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan; Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
Takashi Nemoto
Clinical Laboratory Department, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
Moto Kimura
Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
Sho Saito
Department of Disease Control Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
Shinichiro Morioka
Department of Disease Control Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
Maeda Kenji
Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan; Division of Antiviral Therapy, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Japan
Hiroaki Mitsuya
Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan; Experimental Retrovirology Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Clinical Sciences, Kumamoto University School of Medicine, Kumamoto, Japan
Norio Ohmagari
Department of Disease Control Center, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan
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-EC50 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.
