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Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies.
Cell Host Microbe. 2021 Feb 25 [Online ahead of print]CH

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC50 range, 0.0007-0.35 μg/mL) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain (RBD). Prophylactic intraperitoneal or intranasal injection of individual HuNAb or DNA vaccination significantly reduces infection in the lungs but not in the nasal turbinates of hamsters intranasally challenged with SARS-CoV-2. Although postchallenge HuNAb therapy suppresses viral loads and lung damage, robust infection is observed in nasal turbinates treated within 1-3 days. Our findings demonstrate that systemic HuNAb suppresses SARS-CoV-2 replication and injury in lungs; however, robust viral infection in nasal turbinate may outcompete the antibody with significant implications to subprotection, reinfection, and vaccine.

Authors+Show Affiliations

AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Carol Yu Center for Infection, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Clinical Microbiology and Infection Control, the University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center and School of Medicine, and Vanke School of Public Health, Tsinghua University, Beijing, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Carol Yu Center for Infection, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Carol Yu Center for Infection, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Clinical Microbiology and Infection Control, the University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center and School of Medicine, and Vanke School of Public Health, Tsinghua University, Beijing, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Carol Yu Center for Infection, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Carol Yu Center for Infection, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Clinical Microbiology and Infection Control, the University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, PRC.Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center and School of Medicine, and Vanke School of Public Health, Tsinghua University, Beijing, PRC.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Carol Yu Center for Infection, The University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Clinical Microbiology and Infection Control, the University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, PRC. Electronic address: kyyuen@hku.hk.AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; State Key Laboratory of Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PRC; Department of Clinical Microbiology and Infection Control, the University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, PRC. Electronic address: zchenai@hku.hk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33657424

Citation

Zhou, Dongyan, et al. "Robust SARS-CoV-2 Infection in Nasal Turbinates After Treatment With Systemic Neutralizing Antibodies." Cell Host & Microbe, 2021.
Zhou D, Chan JF, Zhou B, et al. Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies. Cell Host Microbe. 2021.
Zhou, D., Chan, J. F., Zhou, B., Zhou, R., Li, S., Shan, S., Liu, L., Zhang, A. J., Chen, S. J., Chan, C. C., Xu, H., Poon, V. K., Yuan, S., Li, C., Chik, K. K., Chan, C. C., Cao, J., Chan, C. Y., Kwan, K. Y., ... Chen, Z. (2021). Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies. Cell Host & Microbe. https://doi.org/10.1016/j.chom.2021.02.019
Zhou D, et al. Robust SARS-CoV-2 Infection in Nasal Turbinates After Treatment With Systemic Neutralizing Antibodies. Cell Host Microbe. 2021 Feb 25; PubMed PMID: 33657424.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies. AU - Zhou,Dongyan, AU - Chan,Jasper Fuk-Woo, AU - Zhou,Biao, AU - Zhou,Runhong, AU - Li,Shuang, AU - Shan,Sisi, AU - Liu,Li, AU - Zhang,Anna Jinxia, AU - Chen,Serena J, AU - Chan,Chris Chung-Sing, AU - Xu,Haoran, AU - Poon,Vincent Kwok-Man, AU - Yuan,Shuofeng, AU - Li,Cun, AU - Chik,Kenn Ka-Heng, AU - Chan,Chris Chun-Yiu, AU - Cao,Jianli, AU - Chan,Chun-Yin, AU - Kwan,Ka-Yi, AU - Du,Zhenglong, AU - Lau,Thomas Tsz-Kan, AU - Zhang,Qi, AU - Zhou,Jie, AU - To,Kelvin Kai-Wang, AU - Zhang,Linqi, AU - Ho,David D, AU - Yuen,Kwok-Yung, AU - Chen,Zhiwei, Y1 - 2021/02/25/ PY - 2020/12/21/received PY - 2021/02/01/revised PY - 2021/02/19/accepted PY - 2021/3/3/entrez PY - 2021/3/4/pubmed PY - 2021/3/4/medline KW - COVID-19 KW - SARS-CoV-2 KW - human neutralizing antibody KW - lung injury KW - nasal turbinate KW - phage display KW - receptor binding domain KW - upper respiratory tract JF - Cell host & microbe JO - Cell Host Microbe N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a burst in the upper respiratory portal for high transmissibility. To determine human neutralizing antibodies (HuNAbs) for entry protection, we tested three potent HuNAbs (IC50 range, 0.0007-0.35 μg/mL) against live SARS-CoV-2 infection in the golden Syrian hamster model. These HuNAbs inhibit SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain (RBD). Prophylactic intraperitoneal or intranasal injection of individual HuNAb or DNA vaccination significantly reduces infection in the lungs but not in the nasal turbinates of hamsters intranasally challenged with SARS-CoV-2. Although postchallenge HuNAb therapy suppresses viral loads and lung damage, robust infection is observed in nasal turbinates treated within 1-3 days. Our findings demonstrate that systemic HuNAb suppresses SARS-CoV-2 replication and injury in lungs; however, robust viral infection in nasal turbinate may outcompete the antibody with significant implications to subprotection, reinfection, and vaccine. SN - 1934-6069 UR - https://www.unboundmedicine.com/medline/citation/33657424/Robust_SARS-CoV-2_infection_in_nasal_turbinates_after_treatment_with_systemic_neutralizing_antibodies. L2 - https://linkinghub.elsevier.com/retrieve/pii/S1931-3128(21)00098-6 DB - PRIME DP - Unbound Medicine ER -
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