Robust SARS-CoV-2 Infection in Nasal Turbinates after Treatment with Systemic Neutralizing Antibodies

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

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.