Antibody responses to SARS-CoV-2 nucleocapsid and spike proteins in hospitalized patients with COVID-19: A multicenter, retrospective, cross-sectional study in Japan

Background: There are many commercially available automated assays for assessing coronavirus disease 2019 (COVID-19) immune responses; however, owing to insufficient data, their validities remain unknown. Here, we examined antibody responses during acutephase COVID-19 using four assays that detect anti-spike protein IgM (S-IgM), anti-nucleocapsid protein IgG (N-IgG), anti-spike protein total Ig (S-total Ig), and anti-spike protein IgG (S-IgG). Methods: We measured antibody levels in 1154 serum samples collected from 286 hospitalized patients with confirmed COVID-19 by a gene amplification method between February and December 2020 in Japan. Sera from 860 healthcare workers were used as negative controls. Results: The antibody positivity rates increased on week 2, peaked, and then started to plateau by the beginning of week 3 after symptom onset. On week 1, there were some significant differences in seropositivity rates between assays (p = 0.032): 14.9% (11.0% -19.4%) for S-IgM and 8.9% (6.0%-12.7%) for N-IgG. The seropositivity for the S-total Ig (10.6% [7.3%-14.6%]) assay was considerably better than that for the S-IgG (6.9% [4.3% -10.4%]) assay, although the difference was not statistically significant (p = 0.150). The levels of S-IgM antibodies and the three others peaked on weeks 3 and 5, respectively. All four assays showed high specificities (>99%). Conclusions: All four assays had good specificities and were suitable for seropositivity detection after week 3 of symptom onset. Assays of IgM alone or total Ig (containing IgM) were better than those of IgG alone as an adjunct serological test for early-stage COVID-19 diagnosis, albeit the use of a serological assay alone is insufficient. (C) 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.