Université de Paris, IAME, INSERM, Paris, France.
Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses & Le Kremlin-Bicêtre, France.
PLoS Comput Biol. 2021 Mar 17;17(3):e1008785. doi: 10.1371/journal.pcbi.1008785. eCollection 2021 Mar.
Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large burst size (>104 virus) and a within-host reproductive basic number of approximately 6 and 4 in nasopharyngeal and tracheal compartment, respectively. After peak viral load, infected cells were rapidly lost with a half-life of 9 hours, with no significant association between cytokine elevation and clearance, leading to a median time to viral clearance of 10 days, consistent with observations in mild human infections. Given these parameter estimates, we predict that a prophylactic treatment blocking 90% of viral production or viral infection could prevent viral growth. In conclusion, our results provide estimates of SARS-CoV-2 viral kinetic parameters in an experimental model of mild infection and they provide means to assess the efficacy of future antiviral treatments.
非人类灵长类动物感染 SARS-CoV-2 后会出现轻微的临床症状。在这里，我们使用数学模型详细描述了 31 只猕猴的病毒动力学特征，这些猕猴的鼻咽和气管病毒载量经常被评估。我们发现感染细胞的爆发量很大（>104 病毒），鼻咽和气管腔室中的宿主内繁殖基本数分别约为 6 和 4。在病毒载量达到峰值后，感染细胞迅速丢失，半衰期为 9 小时，细胞因子升高与清除之间没有显著关联，导致病毒清除的中位时间为 10 天，与轻度人类感染的观察结果一致。鉴于这些参数估计，我们预测阻断 90%病毒产生或病毒感染的预防性治疗可以防止病毒生长。总之，我们的研究结果提供了轻度感染实验模型中 SARS-CoV-2 病毒动力学参数的估计值，并为评估未来抗病毒治疗的疗效提供了手段。
