van Dorp Christiaan H, Goldberg Emma E, Hengartner Nick, Ke Ruian, Romero-Severson Ethan O
Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos NM, USA.
New Mexico Consortium, Los Alamos NM, USA.
medRxiv. 2021 Sep 24:2021.03.29.21254233. doi: 10.1101/2021.03.29.21254233.
Controlling the SARS-CoV-2 pandemic becomes increasingly challenging as the virus adapts to human hosts through the continual emergence of more transmissible variants. Simply observing that a variant is increasing in frequency is relatively straightforward, but more sophisticated methodology is needed to determine whether a new variant is a global threat and the magnitude of its selective advantage. We present three methods for quantifying the strength of selection for new and emerging variants of SARS-CoV-2 relative to the background of contemporaneous variants. These methods range from a detailed model of dynamics within one country to a broad analysis across all countries, and they include alternative explanations such as migration and drift. We find evidence for strong selection favoring the D614G spike mutation and B.1.1.7 (Alpha), weaker selection favoring B.1.351 (Beta), and no advantage of R.1 after it spreads beyond Japan. Cutting back data to earlier time horizons reveals large uncertainty very soon after emergence, but that estimates of selection stabilize after several weeks. Our results also show substantial heterogeneity among countries, demonstrating the need for a truly global perspective on the molecular epidemiology of SARS-CoV-2.
随着新冠病毒（SARS-CoV-2）通过不断出现更具传播性的变体来适应人类宿主，控制该疫情变得越来越具有挑战性。仅仅观察到某个变体的频率在增加相对简单，但需要更复杂的方法来确定一个新变体是否构成全球威胁及其选择优势的大小。我们提出了三种方法，用于量化新冠病毒新出现变体相对于同期变体背景的选择强度。这些方法从一个国家内动态的详细模型到对所有国家的广泛分析，并且它们包括迁移和漂变等其他解释。我们发现有证据表明强烈选择有利于D614G刺突突变和B.1.1.7（阿尔法）变体，较弱选择有利于B.1.351（贝塔）变体，而R.1变体在传播到日本以外地区后没有优势。将数据回溯到更早的时间范围会发现在出现后很快就存在很大的不确定性，但选择估计在几周后会稳定下来。我们的结果还显示各国之间存在很大的异质性，这表明需要对新冠病毒的分子流行病学有一个真正的全球视角。
