Modelling upper respiratory viral load dynamics of SARS-CoV-2.
Modelling upper respiratory viral load dynamics of SARS-CoV-2.
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DOI：
10.1186/s12916-021-02220-0
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发表时间：
2022-01-13
期刊：
影响因子：
9.3
通讯作者：
Cunnington AJ
中科院分区：
文献类型：
--
作者：
Challenger JD;Foo CY;Wu Y;Yan AWC;Marjaneh MM;Liew F;Thwaites RS;Okell LC;Cunnington AJ
病毒载量、疾病严重程度和病毒传播性之间的关系对于理解COVID-19的发病机制和制定更好的治疗和预防策略至关重要。在这里，我们提出了在上呼吸道（URT）中观察到的病毒载量动态的宿主内建模，从17个不同的研究中收集了605名受试者的2172个连续测量值。我们开发了一种机制模型来描述病毒载量动态和宿主反应，并将其与峰值病毒载量及其随后下降的简单混合效应回归分析进行对比。我们观察到，在症状发作后的任何给定时间点，个体之间的URT病毒载量存在很大差异，超过5个数量级。这种变化不能用年龄、性别或疾病的严重程度来解释，这些变量与免疫介导的病毒载量控制的早期或晚期模型无关。我们探讨了应用机制模型来确定与病毒载量控制相关的免疫反应。在产生中和抗体的受试者中，中和抗体与病毒载量的模拟免疫介导控制密切相关。我们的模型可用于识别控制URT病毒载量动态的宿主和病毒因素，为未来的治疗和传播阻断干预提供信息。在线版本包含补充材料，可通过10.1186/s12916-021-02220-0获得。
Relationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions. The online version contains supplementary material available at 10.1186/s12916-021-02220-0.
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