The serological diversity of serum IgG/IgA/IgM against SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan

Yudai Kaneko; Akira Sugiyama; Toshiya Tanaka; Kazushige Fukui; Akashi Taguchi; Kenji Tatsuno; Aya Nakayama; Kazumasa Koga; Yoshiro Kishi; Wang Daming; Chungen Qian; Fuzhen Xia; Fan He; Liang Zheng; Yi Yu; Youichiro Wada; Yoshiaki Wada; Tatsuhiko Kodama; Takeshi Kawamura

doi:10.1002/hsr2.572

The serological diversity of serum IgG/IgA/IgM against SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan

Health Sci Rep. 2022 Apr 13;5(3):e572. doi: 10.1002/hsr2.572. eCollection 2022 May.

Authors

Yudai Kaneko^{1

2}, Akira Sugiyama^{1

3}, Toshiya Tanaka¹, Kazushige Fukui³, Akashi Taguchi¹, Kenji Tatsuno¹, Aya Nakayama³, Kazumasa Koga⁴, Yoshiro Kishi², Wang Daming⁵, Chungen Qian⁶, Fuzhen Xia⁷, Fan He⁷, Liang Zheng⁷, Yi Yu⁷, Youichiro Wada^{1

3}, Yoshiaki Wada⁴, Tatsuhiko Kodama¹, Takeshi Kawamura^{1

3}

Affiliations

¹ Research Center for Advanced Science and Technology (RCAST) The University of Tokyo Tokyo Japan.
² Medical & Biological Laboratories Co. Ltd Tokyo Japan.
³ Isotope Science Center The University of Tokyo Tokyo Japan.
⁴ Department of Neurology Nissan Tamagawa Hospital Tokyo Japan.
⁵ Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences Suzhou China.
⁶ Department of Biomedical Engineering, The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme College of Life Science and Technology, Huazhong University of Science and Technology Hubei China.
⁷ Reagent R&D Center Shenzhen YHLO Biotech Co. Ltd Guangdong China.

Abstract

Background: We compared the temporal changes of immunoglobulin M (IgM), IgG, and IgA antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (N), spike 1 subunit (S1), and receptor-binding domain (RBD), and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19) to understand the humoral immunity in COVID-19 patients for developing drugs and vaccines for COVID-19.

Methods: A total of five confirmed COVID-19 cases in Nissan Tamagawa Hospital in early August 2020 were recruited in this study. Using a fully automated chemiluminescence immunoassay analyzer, we measured the levels of IgG, IgA, and IgM against SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2 in COVID-19 patients' sera acquired multiple times in individuals from 0 to 76 days after symptom onset.

Results: IgG levels against SARS-CoV-2 structural proteins increased over time in all cases but IgM and IgA levels against SARS-CoV-2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA increasing before IgG and IgM in some cases. The NAb levels were more than cut-off value in 4/5 COVID-19 patients some of whose antibodies against RBD did not exceed the cut-off value in the early stage. Furthermore, NAb levels against SARS-CoV-2 increased and kept above cut-off value more than around 70 days after symptom onset in all cases.

Conclusion: Our findings indicate COVID-19 patients should be examined for IgG, IgA, and IgM against SARS-CoV-2 structural proteins and NAbs against SARS-CoV-2 to analyze the diversity of patients' immune mechanisms.

Keywords: COVID‐19; SARS‐CoV‐2; antibody; neutralizing antibody; patient.