Phenotypic evolution of SARS-CoV-2: A statistical inference approach

Since its emergence in late 2019, the SARS-CoV-2 virus has spread globally, causing the ongoing COVID-19 pandemic. In the fall of 2020, the Alpha variant (lineage B.1.1.7) was detected in England and spread rapidly, outcompeting the previous lineage. Yet, very little is known about the underlying modifications of the infection process that can explain this selective advantage. Here, we try to quantify how the Alpha variant differed from its predecessor on two phenotypic traits: the transmission rate and the duration of infectiousness. To this end, we analysed the joint epidemiological and evolutionary dynamics as a function of the Stringency Index, a measure of the amount of Non-Pharmaceutical Interventions. Assuming that these control measures reduce contact rates and transmission, we developed a two-step approach based on SEIR models and the analysis of a combination of epidemiological and evolutionary information. First, we quantify the link between the Stringency Index and the reduction in viral transmission. Secondly, based on a novel theoretical derivation of the selection gradient in an SEIR model, we infer the phenotype of the Alpha variant from its frequency changes. We show that its selective advantage is more likely to result from a higher transmission than from a longer infectious period. Our work illustrates how the analysis of the joint epidemiological and evolutionary dynamics of infectious diseases can help understand the phenotypic evolution driving pathogen adaptation.

Methods
We only used publicly available data.

自2019年末首次出现以来，严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）已在全球范围内持续传播，引发了至今仍未结束的新型冠状病毒肺炎（COVID-19）大流行。2020年秋季，Alpha变异株（谱系B.1.1.7）在英国被检测发现，并快速扩散，在竞争中击败了此前的主流毒株谱系。然而，目前学界对能够解释该变异株选择优势的感染过程底层调控机制仍知之甚少。本研究旨在量化Alpha变异株与其亲本毒株在两项表型性状上的差异：传播速率与传染期时长。为此，我们以严格指数（Stringency Index，即衡量非药物干预措施（Non-Pharmaceutical Interventions）强度的指标）为自变量，分析了传染病的联合流行病学与进化动力学特征。基于"此类防控措施可降低人群接触率与病毒传播效率"的假设，我们开发了一套基于易感-暴露-感染-恢复（SEIR）模型的两步分析方法，并结合流行病学与进化信息开展联合解析。第一步，我们量化了严格指数与病毒传播效率降幅之间的关联；第二步，基于易感-暴露-感染-恢复模型中选择梯度的全新理论推导，我们通过Alpha变异株的人群频率变化推断其表型特征。研究结果显示，该变异株的选择优势更可能源于更高的传播速率，而非更长的传染期。本研究阐明了对传染病联合流行病学与进化动力学的分析，如何助力解析驱动病原体适应性进化的表型演化机制。

方法
本研究仅使用公开可获取的数据集。