The impact of immune escape on the epidemiology and evolutionary dynamics of the COVID-19 pandemic in Yucatan, Mexico

免疫逃逸对墨西哥尤卡坦半岛 COVID-19 大流行的流行病学和进化动态的影响

基本信息

项目摘要

PROJECT SUMMARY: More than two years after the beginning of the COVID-19 pandemic caused by SARS-CoV-2, more than 600 million cases and 6.5 million deaths have been reported worldwide. Genomic and epidemiological analyses of SARS-CoV-2 have provided key understanding of the emergence and evolutionary processes that drive viral mutations and promote antigenic escape and enhanced virus transmission. Preliminary studies reported increased transmissibility for SARS-CoV-2 lineages with the D614G mutation 1, as well as the variants of concern (VOC) Alpha/B.1.1.7, Beta/B.1.351, Gamma/P.1 and Delta/B.1.617.2. The emergence and unprecedented speed of transmission of the VOC Omicron/B.1.1.529 resulted in a significant number of cases worldwide and breakthrough infections in a high proportion of vaccinated individuals. Therefore, there is a continued need to monitor the genomic characteristics of circulating viruses for early identification of new variants with altered immune, transmission or pathogenicity properties, particularly in settings with high infection rates. Mexico ranks third in Latin America in terms of COVID-19 burden with more than 7 million cases as of November 3, 2022, and third worldwide in total number of reported COVID-19 related deaths, with fatalities above 330,000. The COVID-19 pandemic has underlined the gaps in the current surveillance system in Mexico. The genomic epidemiology of SARS-CoV-2 in Mexico is underrepresented and undercharacterized due to limited spatial coverage of viral genomes. Genetic differences between the circulating SARS-CoV-2 viruses in Mexico, the Americas and globally are unclear. Mexico is a vast and diverse country with differences in demography, climate, and significant population mobility, both domestically and internationally, recording 32.4 million US tourists in 2019 5. Our previous work on influenza virus in Yucatan showed strong evidence that seasonality and the occurrence of genetic variants vary greatly across the country, which encompasses temperate and tropical regions 6,7. Thus examining the genomic epidemiology of SARS-CoV-2 in Mexico, particularly in highly touristic states such as Yucatan, will shed light on the viral diversity and transmission dynamics in the country, and clarify evolutionary changes as the disease becomes endemic. Because of tight connections between Mexico and the US, these analyses will also contribute to informing public health interventions in both nations. This project leverages existing and newly generated data on SARS-CoV-2 in Yucatan and consequently in Mexico, enabling: 1) epidemiological and mathematical modeling to evaluate changes in viral dissemination and diversity in the context of vaccination campaigns and changes in population mobility, and estimate the fitness advantage of new variants on a population level, and 2) characterize circulating variants by generating genomic sequences and reconstructing the evolutionary history and migrations that led to the emergence or introduction of locally circulating lineages. Genomic and phylodynamic analysis, in conjunction with mathematical modeling, have provided powerful tools to understand and predict the fate of new SARS-CoV-2 variants elsewhere 8. An integrated capacity for outbreak analytics combining genomics, phylodynamics and mathematical modeling is lacking in Yucatan, Mexico. This work will build local capacity to address these questions and have a significant public health impact by providing accurate information about COVID-19 transmission dynamics.
项目总结: 在由SARS-CoV-2引发的新冠肺炎大流行开始两年多后,更多 全球报告的病例超过6亿例,死亡650万人。基因组和 对SARS-CoV-2的流行病学分析提供了对SARS-CoV-2出现和 驱动病毒突变并促进抗原逃逸和增强病毒的进化过程 变速箱。初步研究报告称,随着SARS-CoV-2基因谱系的增加,其传播性增加 D614G突变1以及关注的变异体(VOC)Alpha/B.1.1.7、Beta/B.1.351、Gamma/P.1 和Delta/B.1.617.2。VOC的出现和前所未有的传播速度 Omicron/B.1.1.529导致全球大量病例和#年突破性感染 接种疫苗的个人比例很高。因此,继续需要对基因组进行监测 用于早期识别免疫改变的新变种的流行病毒的特征, 传播或致病特性,特别是在高感染率的环境中。墨西哥排名 截至11月3日,在新冠肺炎负担方面,拉丁美洲排名第三,有700多万例, 2022年,报告的新冠肺炎相关死亡总数全球第三,以上死亡人数 33万。新冠肺炎疫情突显了当前监测系统在 墨西哥。墨西哥SARS-CoV-2的基因组流行病学未得到充分代表 由于病毒基因组的空间复盖面有限,特征不足。不同性别间的遗传差异 目前尚不清楚在墨西哥、美洲和全球传播的SARS-CoV-2病毒。墨西哥是一个辽阔的 和多样化的国家,在人口结构、气候和显著的人口流动方面存在差异,两者 国内和国际,2019年记录了3240万美国游客5。我们之前在 流感病毒在尤卡坦显示出强烈的季节性和遗传性的发生 变种在全国范围内差异很大,包括温带和热带地区6,7。 检查墨西哥SARS-CoV-2的基因组流行病学,特别是在高度旅游的州 例如尤卡坦半岛,将揭示该国的病毒多样性和传播动态,以及 随着疾病的流行,阐明进化的变化。因为它们之间有着紧密的联系 在墨西哥和美国,这些分析也将有助于为这两个国家的公共卫生干预提供信息 国家。 该项目利用了尤卡坦现有的和新生成的关于SARS-CoV-2的数据和 因此,在墨西哥,能够:1)流行病学和数学建模以评估 疫苗接种运动背景下病毒传播和多样性的变化以及 种群流动性,并在种群水平上估计新变种的适应优势,以及2) 通过生成基因组序列并重建 导致地方流通出现或引入的进化史和迁徙 血统。基因组和系统动力学分析,与数学建模相结合, 为理解和预测其他地方新的SARS-CoV-2变种的命运提供了强大的工具8。 结合基因组学、系统动力学和 在墨西哥的尤卡坦,数学建模是欠缺的。这项工作将建设当地能力,以 解决这些问题,并通过提供准确的 有关新冠肺炎传输动态的信息。

项目成果

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