Background Monoclonal antibodies (mAbs) represent a crucial antiviral strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether combination mAbs offer a benefit over single-active mAb treatment. Amubarvimab and romlusevimab significantly reduced the risk of hospitalizations or death in the ACTIV-2/A5401 trial. Certain SARS-CoV-2 variants are intrinsically resistant against romlusevimab, leading to only single-active mAb therapy with amubarvimab in these variants. We evaluated virologic outcomes in individuals treated with single- versus dual-active mAbs. Methods Participants were nonhospitalized adults at higher risk of clinical progression randomized to amubarvimab plus romlusevimab or placebo. Quantitative SARS-CoV-2 RNA levels and targeted S-gene next-generation sequencing was performed on anterior nasal samples. We compared viral load kinetics and resistance emergence between individuals treated with effective single- versus dual-active mAbs depending on the infecting variant. Results Study participants receiving single- or dual-active mAbs had similar demographics, baseline nasal viral load, symptom score, and symptom duration. Compared with single-active mAb treatment, treatment with dual-active mAbs led to faster viral load decline at study days 3 (P < .001) and 7 (P < .01). Treatment-emergent resistance mutations were more likely to be detected after amubarvimab plus romlusevimab treatment than with placebo (2.6% vs 0%; P < .001) and were more frequently detected in the setting of single-active compared with dual-active mAb treatment (7.3% vs 1.1%; P < .01). Single-active and dual-active mAb treatment resulted in similar decrease in rates of hospitalizations or death. Conclusions Compared with single-active mAb therapy, dual-active mAbs led to similar clinical outcomes but significantly faster viral load decline and a lower risk of emergent resistance.

中文翻译：

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针对严重急性呼吸系统综合症冠状病毒 2 的单活性单克隆抗体与双活性单克隆抗体的治疗耐药性和病毒动力学特征


背景单克隆抗体 （mAb） 是严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 感染的重要抗病毒策略，但尚不清楚联合 mAb 是否比单一活性 mAb 治疗具有益处。在 ACTIV-2/A5401 试验中，安巴韦单抗和罗米司韦单抗显著降低了住院或死亡的风险。某些 SARS-CoV-2 变体对罗米司韦单抗具有内在耐药性，导致在这些变体中仅使用安巴韦单抗进行单活性 mAb 治疗。我们评估了单活性 mAb 与双活性 mAb 治疗个体的病毒学结局。方法 参与者是临床进展风险较高的非住院成年人，随机接受安巴韦单抗加罗米司韦单抗或安慰剂组。对前鼻样本进行定量 SARS-CoV-2 RNA 水平和靶向 S 基因下一代测序。我们根据感染变异比较了接受有效单活性和双活性 mAb 治疗的个体之间的病毒载量动力学和耐药性出现。结果 接受单活性或双活性 mAb 的研究参与者具有相似的人口统计学、基线鼻病毒载量、症状评分和症状持续时间。与单活性 mAb 处理相比，双活性 mAb 处理导致研究第 3 天 （P < .001） 和 7 （P < .01） 病毒载量下降更快。与安慰剂相比，安巴韦单抗联合罗米司韦单抗治疗后更有可能检测到治疗中出现的耐药突变（2.6% 对 0%;P < .001），与双活性 mAb 处理相比，在单活性 mAb 处理的情况下更频繁地检测到 （7.3% 对 1.1%;P < .01）.单活性和双活性 mAb 治疗导致住院率或死亡率的降低相似。 结论 与单活性 mAb 治疗相比，双活性 mAb 导致相似的临床结局，但病毒载量下降速度显著加快，紧急耐药风险降低。