Antibody Responses and Clinical Outcomes in Adults Hospitalized with Severe COVID-19: A Post hoc Analysis of LOTUS China Trial

Ren, Lili; Fan, Guohui; Wu, Wenjuan; Guo, Li; Wang, Yeming; Li, Xia; Wang, Conghui; Gu, Xiaoying; Li, Caihong; Wang, Ying; Wang, Geng; Zhou, Fei; Liu, Zhibo; Ge, Qing; Zhang, Yi; Li, Hui; Zhang, Lulu; Xu, Jiuyang; Wang, Chen; Wang, Jianwei; Cao, Bin

BACKGROUND: The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe COVID-19 patients were still less known METHODS: The neutralizing antibodies (NAbs) and antibodies targeting nucleocapsid (N), spike protein (S), and the receptor-binding domain (RBD) in longitudinal plasma samples from the LOTUS China trial were measured by microneutralization assay and ELISA. Viral load was determined by real-time RT-PCR. A total of 576 plasma and 576 throat swabs were collected from 191 COVID-19 patients. Antibody titers related to adverse outcome and clinical improvement were analysed. Multivariable adjusted generalized linear mixed model for random effects were developed RESULTS: After day 28 post symptoms onset, the rate of antibody positivity reached 100% for RBD-IgM, 97.8% for S-IgM, 100% for N-IgG, 100% for RBD-IgG, 91.1% for N-IgM and 91.1% for NAbs. The NAbs titers increased over time in both survivors and non-survivors and correlated to IgG antibodies against N, S and RBD, while its presence showed no statistical correlation with death. N-IgG (slope -2.11, 95% CI -3.04 to -1.18, p&0.0001), S-IgG (slope -2.44, 95% CI -3.35 to -1.54, p&0.0001) and RBD-IgG (slope -1.43, 95% CI -1.98 to -0.88, p&0.0001) were negatively correlated with viral load. S-IgG titers were lower in non-survivors than survivors (p=0.020) at week 4 after symptoms onset CONCLUSIONS: IgM, IgG against N, S and RBD and NAbs developed in most severe COVID-19 patients, and do not correlate clearly with clinical outcomes. The levels of IgG antibodies against N, S and RBD were related to viral clearance