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Cross-Reactive Antibody Against Human Coronavirus OC43 Spike Protein Correlates with Disease Severity in COVID-19 Patients: A Retrospective Study

44 Pages Posted: 10 Oct 2020

See all articles by Li Guo

Li Guo

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Yeming Wang

China-Japan Friendship Hospital - Department of Pulmonary and Critical Care Medicine

Liang Kang

Jin Yin-tan Hospital

Yongfeng Hu

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Linghang Wang

Capital Medical University - Clinical and Research Center of Infectious Disease

Jingchuan Zhong

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Hong Chen

Harbin Medical University - Second Affiliated Hospital

Lili Ren

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Xiaoying Gu

China-Japan Friendship Hospital - Institute of Clinical Medical Sciences

Geng Wang

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

conghui wang

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Xiaojing Dong

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Chao Wu

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Ying Wang

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Guohui Fan

China-Japan Friendship Hospital

Xiaohui Zou

China-Japan Friendship Hospital - Department of Pulmonary and Critical Care Medicine

Haibo Li

China-Japan Friendship Hospital - Department of Pulmonary and Critical Care Medicine

Jiuyang Xu

China-Japan Friendship Hospital - Institute of Clinical Medical Sciences

Qi Jin

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Bin Cao

China-Japan Friendship Hospital - Department of Pulmonary and Critical Care Medicine

Jianwei Wang

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

More...

Abstract

Background: Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63 and -HKU1 are widely spreading in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive.

Methods: We profiled the temporal changes of IgG antibodies against spike (S; S-IgG) proteins of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivity of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between HCoV-OC43 S-IgG antibody  and disease severity in COVID-19 patients.

Findings: SARS-CoV-2 S-IgG titers mounted until days 22–28, whereas HCoV-OC43 antibody titers increased until days 15–21 and then plateaued until day 46. However, IgG antibody titers against HCoV-NL63, -229E, and -HKU1 showed no significant increasing. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detected in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titers were significantly higher in patients with severe disease than those in mild/moderate patients at days 1–21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation and the elderly. At days 1–10 PSO, HCoV-OC43 S-IgG titers correlated to disease severity in all age groups, and to fatality in over 60-year group.

Interpretation: Our data indicate that there exist a humoral cross-reactive response between HCoV-OC43 and SARS-CoV-2. The cross-reactive HCoV-OC43 S-IgG antibody is not protective against SARS-CoV-2, but may be a risk factor for the severity and adverse outcome of COVID-19.

Funding Statement: This study was funded in part by the National Major Science & Technology Project for Control and Prevention of Major Infectious Diseases in China (2017ZX10204401, 2018ZX10734404), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2016-I2M-1–014, 2018-I2M-1-003, 2020-I2M-1-001, 2020-I2M-CoV19-005), Natural Science Foundation of China (82041011/H0104), and National Key R&D Program of China (2020YFA0707600).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: This study was approved by the Ethical Review Board of Wuhan Jinyintan Hospital, Infectious Disease Hospital of Heilongjiang Province (Harbin), and Institute of Pathogen Biology, Chinese Academy of Medical Sciences. Written informed consent was obtained from each healthy volunteer and COVID-19 patients in cohort 4. Written informed consents from the remaining patients were waived in light of the emerging infectious disease of high public health relevance.

Keywords: cross-reactivity, antibody, antibody, HCoV-OC43, SARS-CoV-2, disease severity

Suggested Citation

Guo, Li and Wang, Yeming and Kang, Liang and Hu, Yongfeng and Wang, Linghang and Zhong, Jingchuan and Chen, Hong and Ren, Lili and Gu, Xiaoying and Wang, Geng and wang, conghui and Dong, Xiaojing and Wu, Chao and Wang, Ying and Fan, Guohui and Zou, Xiaohui and Li, Haibo and Xu, Jiuyang and Jin, Qi and Cao, Bin and Wang, Jianwei, Cross-Reactive Antibody Against Human Coronavirus OC43 Spike Protein Correlates with Disease Severity in COVID-19 Patients: A Retrospective Study. Available at SSRN: https://ssrn.com/abstract=3676223 or http://dx.doi.org/10.2139/ssrn.3676223

Li Guo

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Beijing
China

Yeming Wang

China-Japan Friendship Hospital - Department of Pulmonary and Critical Care Medicine

Beijing
China

Liang Kang

Jin Yin-tan Hospital

China

Yongfeng Hu

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens ( email )

Beijing
China

Linghang Wang

Capital Medical University - Clinical and Research Center of Infectious Disease ( email )

Beijing, 100015
China

Jingchuan Zhong

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens ( email )

Beijing
China

Hong Chen

Harbin Medical University - Second Affiliated Hospital

Harbin
China

Lili Ren

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Beijing
China

Xiaoying Gu

China-Japan Friendship Hospital - Institute of Clinical Medical Sciences

Beijing
China

Geng Wang

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Beijing
China

Conghui Wang

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens ( email )

Beijing
China

Xiaojing Dong

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Beijing
China

Chao Wu

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Beijing
China

Ying Wang

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens

Beijing
China

Guohui Fan

China-Japan Friendship Hospital

China

Xiaohui Zou

China-Japan Friendship Hospital - Department of Pulmonary and Critical Care Medicine

China

Haibo Li

China-Japan Friendship Hospital - Department of Pulmonary and Critical Care Medicine

China

Jiuyang Xu

China-Japan Friendship Hospital - Institute of Clinical Medical Sciences

Beijing
China

Qi Jin

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens ( email )

Beijing
China

Bin Cao

China-Japan Friendship Hospital - Department of Pulmonary and Critical Care Medicine

China

Jianwei Wang (Contact Author)

Chinese Academy of Medical Sciences - NHC Key Laboratory of Systems Biology of Pathogens ( email )

Beijing
China

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