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Robust SARS-CoV-2 infection in nasal turbinates after treatment with systemic neutralizing antibodies

2021; Cell Press; Volume: 29; Issue: 4 Linguagem: Inglês

10.1016/j.chom.2021.02.019

1934-6069

Dongyan Zhou, Jasper Fuk‐Woo Chan, Biao Zhou, Runhong Zhou, Shuang Li, Sisi Shan, Li Liu, Jinxia Zhang, Serena J. Chen, Chris Chung-Sing Chan, Haoran Xu, Vincent Kwok‐Man Poon, Shuofeng Yuan, Cun Li, Kenn Ka-Heng Chik, Chris Chun-Yiu Chan, Jianli Cao, Chun-Yin Chan, Ka-Yi Kwan, Zhenglong Du, Thomas Tsz-Kan Lau, Qi Zhang, Jie Zhou, Kelvin Kai‐Wang To, Linqi Zhang, David D. Ho, Kwok‐Yung Yuen, Zhiwei Chen,

SARS-CoV-2 detection and testing

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.