Within-host SARS-CoV-2 viral kinetics informed by complex life course exposures reveals different intrinsic properties of Omicron and Delta variants.
Within-host SARS-CoV-2 viral kinetics informed by complex life course exposures reveals different intrinsic properties of Omicron and Delta variants.
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通过复杂的生命历程暴露了解的宿主内 SARS-CoV-2 病毒动力学揭示了 Omicron 和 Delta 变体的不同内在特性。
DOI：
10.1101/2023.05.17.23290105
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Russell TW
中科院分区：
文献类型：
--
作者：
Russell TW
2020- 2022年期间连续出现的SARS-CoV-2关注变体（VOC），每种变体都表现出相对于早期流行变体的流行增长，因此需要了解这种增长的驱动因素。然而，病原体生物学和不断变化的宿主特征--如不同的免疫水平--可以联合收割机结合起来影响SARS-CoV-2在宿主内和宿主之间的复制和传播。解开变异体和宿主在VOCs个体水平病毒脱落中的作用，对于为COVID-19规划和应对提供信息以及解释过去的流行趋势至关重要。使用来自健康成年志愿者的前瞻性观察性队列研究的数据，每周进行职业健康PCR筛查，我们开发了贝叶斯分层模型来重建个体水平的病毒动力学，并估计不同因素如何塑造病毒动力学，通过PCR循环阈值（Ct）随时间的变化来测量。综合考虑Ct值的个体间变异和复杂的宿主特征（如疫苗接种状态、暴露史和年龄），我们发现年龄和既往暴露次数对病毒复制峰值有很大影响。年龄较大的个体和那些先前至少有五次抗原暴露于疫苗接种和/或感染的个体通常具有低得多的脱落水平。此外，当比较不同的VOCs和年龄组时，我们发现了早期脱落速度和潜伏期持续时间之间相关性的证据。我们的研究结果说明了将参与者特征，症状特征和感染变体与前瞻性PCR采样联系起来的价值，以及在分析VOC病毒动力学时考虑日益复杂的人群暴露景观的重要性。
The emergence of successive SARS-CoV-2 variants of concern (VOC) during 2020-22, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics – such as varying levels of immunity – can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform COVID-19 planning and response, and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both inter-individual variation in Ct values and complex host characteristics – such as vaccination status, exposure history and age – we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least five prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs.