Neutralizing antibodies (NAbs) are effective in treating COVID-19, but the mechanism of immune protection is not fully understood. Here, we applied live bioluminescence imaging (BLI) to monitor the real-time effects of NAb treatment during prophylaxis and therapy of K18-hACE2 mice intranasally infected with SARS-CoV-2-nanoluciferase. Real-time imaging revealed that the virus spread sequentially from the nasal cavity to the lungs in mice and thereafter systemically to various organs including the brain, culminating in death. Highly potent NAbs from a COVID-19 convalescent subject prevented, and also effectively resolved, established infection when administered within three days. In addition to direct neutralization, depletion studies indicated that Fc effector interactions of NAbs with monocytes, neutrophils, and natural killer cells were required to effectively dampen inflammatory responses and limit immunopathology. Our study highlights that both Fab and Fc effector functions of NAbs are essential for optimal in vivo efficacy against SARS-CoV-2.

中和抗体 (NAb) 可有效治疗 COVID-19，但免疫保护机制尚不完全清楚。在这里，我们应用实时生物发光成像 (BLI) 来监测 NAb 治疗在预防和治疗鼻内感染 SARS-CoV-2-纳米荧光素酶的 K18-hACE2 小鼠期间的实时效果。实时成像显示，病毒在小鼠体内依次从鼻腔传播到肺部，然后全身传播到包括大脑在内的各种器官，最终导致死亡。来自 COVID-19 恢复期受试者的高效 NAb 在三天内给药时可预防并有效解决已建立的感染。除了直接中和，耗竭研究表明，NAb 与单核细胞、中性粒细胞、自然杀伤细胞需要有效抑制炎症反应并限制免疫病理学。我们的研究强调，NAb 的 Fab 和 Fc 效应器功能对于优化体内抗 SARS-CoV-2 的功效。