Regeneron Pharmaceuticals, Tarrytown, New York, USA.
Certara, Paris, France.
Clin Pharmacol Ther. 2022 Dec;112(6):1224-1235. doi: 10.1002/cpt.2728. Epub 2022 Sep 20.
To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April-August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID-19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment-as-prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS-CoV-2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness.
为评估抗病毒单克隆抗体(mAbs)和疫苗联合在降低美国严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)传播和死亡率方面的作用,开发了一个基于代理的模型,该模型考虑了社会接触、移动/旅行、疾病进展和病毒脱落。该模型根据 2020 年 10 月至 2021 年 4 月(积极大流行阶段)的 2019 冠状病毒病(COVID-19)死亡率进行了校准,并预测了一个扩展的前景,以估计在不那么积极的阶段(2021 年 4 月至 8 月)的死亡率。模拟场景评估了 mAbs 在疫苗之外预防感染和死亡的作用,以及聚合的非药物干预措施。这些场景包括将 mAbs 作为 COVID-19 的治疗方法,以及在变体易受 mAbs 影响的时期用于接触后预防(PEP)的被动免疫。快速诊断测试与 mAbs 联合使用被评估为一种早期治疗即预防策略。敏感性分析包括增加 mAb 供应和疫苗接种。仅将 mAb 用于 PEP 的分配避免了多达 14%的感染,而仅针对≥65 岁的人群则避免了多达 37%的死亡。快速检测用于更早诊断和 mAb 使用放大了这些好处。将 mAb 供应增加一倍进一步减少了感染和死亡。即使免疫人群的比例增加,mAb 仍能提供益处。模型预测估计,2021 年 4 月至 8 月期间,预计死亡人数中约有 42%可以避免。假设对 mAbs 敏感,除了疫苗外,将其作为早期治疗和 PEP 使用将大大降低 SARS-CoV-2 的传播和死亡率,即使疫苗接种增加和死亡率降低。这些结果为未来大流行准备的公共卫生政策提供了模板。