Association of the Serum Levels of the Nucleocapsid Antigen of SARS-CoV-2 With the Diagnosis, Disease Severity, and Antibody Titers in Patients With COVID-19: A Retrospective Cross-Sectional Study

Rin Yokoyama; Makoto Kurano; Yuki Nakano; Yoshifumi Morita; Hiroko Ohmiya; Yoshiro Kishi; Jun Okada; Chungen Qian; Fuzhen Xia; Fan He; Liang Zheng; Yi Yu; Miyuki Mizoguchi; Yoshimi Higurashi; Sohei Harada; Daisuke Jubishi; Koh Okamoto; Kyoji Moriya; Tatsuhiko Kodama; Yutaka Yatomi

doi:10.3389/fmicb.2021.791489

Association of the Serum Levels of the Nucleocapsid Antigen of SARS-CoV-2 With the Diagnosis, Disease Severity, and Antibody Titers in Patients With COVID-19: A Retrospective Cross-Sectional Study

Front Microbiol. 2021 Dec 9:12:791489. doi: 10.3389/fmicb.2021.791489. eCollection 2021.

Authors

Rin Yokoyama¹, Makoto Kurano^{1

2}, Yuki Nakano¹, Yoshifumi Morita¹, Hiroko Ohmiya³, Yoshiro Kishi³, Jun Okada³, Chungen Qian⁴, Fuzhen Xia⁵, Fan He⁵, Liang Zheng⁵, Yi Yu⁵, Miyuki Mizoguchi⁶, Yoshimi Higurashi⁶, Sohei Harada⁶, Daisuke Jubishi⁶, Koh Okamoto⁶, Kyoji Moriya⁶, Tatsuhiko Kodama⁷, Yutaka Yatomi^{1

2}

Affiliations

¹ Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan.
² Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³ Sales and Marketing Division, Business Planning Department, Medical and Biological Laboratories Co., Ltd., Tokyo, Japan.
⁴ The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
⁵ Reagent R and D Center, Shenzhen YHLO Biotech Co., Ltd., Guangdong, China.
⁶ Department of Infection Control and Prevention, The University of Tokyo, Tokyo, Japan.
⁷ Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.

Abstract

Background: Several types of laboratory tests for COVID-19 have been established to date; however, the clinical significance of the serum SARS-CoV-2 nucleocapsid (N) antigen levels remains to be fully elucidated. In the present study, we attempted to elucidate the usefulness and clinical significance of the serum N antigen levels. Methods: We measured the serum N antigen levels in 391 serum samples collected from symptomatic patients with a confirmed diagnosis of COVID-19 and 96 serum samples collected from patients with non-COVID-19, using a fully automated chemiluminescence immunoassay analyzer. Results: Receiver operating characteristic analysis identified the optimal cutoff value of the serum N antigen level (cutoff index, based on Youden's index) as 0.255, which yielded a sensitivity and specificity for the diagnosis of COVID-19 of 91.0 and 81.3%, respectively. The serum N antigen levels were significantly higher in the patient groups with moderate and severe COVID-19 than with mild disease. Moreover, a significant negative correlation was observed between the serum N antigen levels and the SARS-CoV-2 IgG antibody titers, especially in patients with severe COVID-19. Conclusion: Serum N antigen testing might be useful both for the diagnosis of COVID-19 and for obtaining a better understanding of the clinical features of the disease.

Keywords: COVID-19; N antigen; antibody titer; coronavirus disease 2019; diagnosis; nucleocapsid antigen; severity.