Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses.
Heterogeneous SARS-CoV-2 kinetics due to variable timing and intensity of immune responses.
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由于免疫反应的时间和强度不同而导致 SARS-CoV-2 动力学异质。
DOI：
10.1101/2023.08.20.23294350
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Schiffer,JoshuaT
中科院分区：
文献类型：
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作者：
Owens,Katherine;Esmaeili-Wellman,Shadisadat;Schiffer,JoshuaT
记录的SARS-CoV-2感染的病毒动力学表现出高度的个体间变异性。通过对来自美国国家篮球协会队列中768例感染的数据进行聚类，我们确定了6种不同的病毒脱落模式，这些模式根据峰值病毒载量、持续时间、扩增率和清除率而不同。在先前接种疫苗的个体中，Omicron变体感染通常导致SARS-CoV-2的累积脱落水平低于其他情况。然后，我们开发了一个机械数学模型，概括了1,510个观察到的病毒轨迹，包括病毒反弹和再感染病例。较低的峰值病毒载量被解释为在感染期间易感细胞更快速和持续地转变为难治性状态，以及更早和更有效的晚期溶细胞免疫应答。我们的研究结果表明，在Omicron感染期间，接种疫苗后和再感染后，由于增强的先天性和获得性免疫应答，病毒消除发生得更快。由于病毒载量与COVID-19的严重程度和传播风险有关，我们的模型为理解广泛的SARS-CoV-2感染结果提供了一个框架。
The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of interindividual variability. We identified 6 distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate, and clearance rate, by clustering data from 768 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1,510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection as well as by an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during Omicron infection, following vaccination, and following reinfection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.