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

Abstract

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