van Dorp Christiaan, Goldberg Emma, Ke Ruian, Hengartner Nick, Romero-Severson Ethan
Department of Pathology & Cell Biology, Columbia University Irving Medical Center, New York NY, USA.
Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos NM, USA.
medRxiv. 2022 Jun 16:2022.06.15.22276436. doi: 10.1101/2022.06.15.22276436.
New variants of SARS-CoV-2 show remarkable heterogeneity in their relative fitness both over time and space. In this paper we extend a previously published model for estimating the selection strength for new SARS-CoV-2 variants to a hierarchical, mixed-effects, renewal equation model. This formulation allows us to globally estimate selection effects at different spatial levels while controlling for complex patterns of transmission and jointly inferring the effects of unit-level covariates in the spatial heterogeneity of SARS-CoV-2 selection effects. Applying this model to the spread of Omicron in 40 counties finding evidence for very strong (64%) but very heterogeneous selection effects at the country level. We further considered different measures of vaccination levels and measures of recent population-level infection as possible explanations. However, none of those variables were found to explain a significant proportion of the heterogeneity in country-level selection effects. We did find a significant positive correlation between the selection advantage of Delta and Omicron at the country level, suggesting that region-specific explanatory variables of fitness differences do exist. Our method is implemented in the Stan programming language, can be run on standard commercial-grade computing resources, and should be straightforward to apply to future variants.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的新变种在其相对适应性方面,无论在时间上还是空间上都表现出显著的异质性。在本文中,我们将先前发表的用于估计SARS-CoV-2新变种选择强度的模型扩展为一个分层、混合效应、更新方程模型。这种公式使我们能够在控制复杂传播模式的同时,在不同空间层面全局估计选择效应,并共同推断单位层面协变量对SARS-CoV-2选择效应空间异质性的影响。将该模型应用于奥密克戎在40个县的传播情况,发现在国家层面存在非常强(64%)但非常异质的选择效应的证据。我们进一步考虑了不同的疫苗接种水平衡量指标以及近期人群感染水平衡量指标,作为可能的解释。然而,这些变量均未被发现能够解释国家层面选择效应异质性的很大一部分。我们确实发现,在国家层面,德尔塔和奥密克戎的选择优势之间存在显著的正相关,这表明确实存在特定区域的适应性差异解释变量。我们的方法是用Stan编程语言实现的,可以在标准商业级计算资源上运行,并且应该很容易应用于未来的变种。