Antibody Responses and Clinical Outcomes in Adults Hospitalized With Severe Coronavirus Disease 2019 (COVID-19): A Post hoc Analysis of LOTUS China Trial

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

doi:10.1093/cid/ciaa1247

Antibody Responses and Clinical Outcomes in Adults Hospitalized With Severe Coronavirus Disease 2019 (COVID-19): A Post hoc Analysis of LOTUS China Trial

Clin Infect Dis. 2021 May 18;72(10):e545-e551. doi: 10.1093/cid/ciaa1247.

Authors

Lili Ren^{1

2}, Guohui Fan^{3

4}, Wenjuan Wu⁵, Li Guo^{1

2}, Yeming Wang^{4

6}, Xia Li⁵, Conghui Wang¹, Xiaoying Gu^{3

4}, Caihong Li⁵, Ying Wang¹, Geng Wang¹, Fei Zhou^{4

6}, Zhibo Liu^{4

6}, Qing Ge⁵, Yi Zhang^{4

6}, Hui Li^{4

6}, Lulu Zhang¹, Jiuyang Xu⁷, Chen Wang^{4

6

8}, Jianwei Wang^{1

2}, Bin Cao^{4

6}

Affiliations

¹ NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
² Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
⁴ Institute of Respiratory Medicine, Chinese Academy of Medical Science, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Diseases, Beijing, China.
⁵ Jin Yin-tan Hospital; Wuhan, Hubei Province, China.
⁶ Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
⁷ Tsinghua University School of Medicine, Beijing, China.
⁸ Peking Union Medical College, Beijing, China.

Abstract

Background: The characteristics of neutralizing antibodies (NAbs) and antibody against major antigen proteins related to clinical outcomes in severe coronavirus disease 2019 (COVID-19) patients were still less known.

Methods: 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 enzyme-linked immunosorbent assay (ELISA). Viral load was determined by real-time reverse transcription polymerase chain reaction (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 analyzed. 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-immunoglobulin M (IgM), 97.8% for S-IgM, 100% for N-immunoglobulin G (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 nonsurvivors and correlated to IgG antibodies against N, S, and RBD, whereas its presence showed no statistical correlation with death. N-IgG (slope -2.11, 95% confidence interval [CI] -3.04 to -1.18, P < .0001), S-IgG (slope -2.44, 95% CI -3.35 to -1.54, P < .0001), and RBD-IgG (slope -1.43, 95% CI -1.98 to -.88, P < .0001) were negatively correlated with viral load. S-IgG titers were lower in nonsurvivors than survivors (P = .020) at week 4 after symptoms onset.

Conclusions: IgM and 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; humoral response; neutralizing antibody; severe COVID-19.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Viral
Antibody Formation
COVID-19*
China / epidemiology
Humans
Immunoglobulin M
SARS-CoV-2

Substances

Antibodies, Viral
Immunoglobulin M