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

Clin Infect Dis. 2020 Aug 25;ciaa1247. doi: 10.1093/cid/ciaa1247. Online ahead of print.

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.

Keywords: LOTUS China; clinical outcomes; dynamic changes; humoral response; neutralizing antibody; severe COVID-19.