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

• 批准号: 10741899
• 负责人: Guadalupe Ayora-Talavera
• 金额: $ 5.15万
• 依托单位: AUTONOMOUS UNIVERSITY OF YUCATAN
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-11 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10741899
• 关键词: 2019-nCoV; Address; Age; Americas; Archives; Authorization documentation; Automobile Driving; COVID-19; COVID-19 mortality; COVID-19 pandemic; Cessation of life; Characteristics; Circulation; Climate; Clinical; Country; Data; Databases; Demography; Disease; Disease Outbreaks; Early identification; Effectiveness; Epidemiological trend; Epidemiology; Event; Genetic; Genomics; Geography; Goals; Health; Immune; International; Intervention; Laboratories; Latin America; Measures; Mexico; Monitor; Mutation; Pathogenicity; Patients; Population; Population Dynamics; Process; Property; Prospective Studies; Public Health; Recording of previous events; Reporting; Reproduction; Reverse Transcription; Route; SARS-CoV-2 B.1.1.529; SARS-CoV-2 B.1.1.7; SARS-CoV-2 B.1.351; SARS-CoV-2 B.1.617.2; SARS-CoV-2 transmission; SARS-CoV-2 variant; Sampling; Seasons; Specimen; Speed; System; Time; Travel; Universities; Vaccination; Vaccinee; Vaccines; Variant; Viral; Viral Genome; Virus; Work; authority; breakthrough infection; comorbidity; data integration; emerging pathogen; epidemiologic data; epidemiological model; fitness; genetic variant; genomic data; genomic epidemiology; infection rate; influenzavirus; interest; mathematical model; migration; public health intervention; repository; response; sex; tool; transmission process; variants of concern; viral transmission; virology

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.

项目概要： 由 SARS-CoV-2 引起的 COVID-19 大流行开始两年多后，更多 全球报告了超过 6 亿例病例和 650 万人死亡。基因组和 SARS-CoV-2 的流行病学分析提供了对 SARS-CoV-2 的出现和发生的关键了解。 驱动病毒突变并促进抗原逃逸和增强病毒的进化过程 传播。初步研究报告称，SARS-CoV-2 谱系的传播性随着 D614G 突变 1，以及受关注的变体 (VOC) Alpha/B.1.1.7、Beta/B.1.351、Gamma/P.1 和德尔塔/B.1.617.2。 VOC的出现和前所未有的传播速度 Omicron/B.1.1.529 在全球范围内导致了大量病例，并在 接种疫苗的人比例很高。因此，需要持续监测基因组 传播病毒的特征，用于早期识别免疫改变的新变种， 传播或致病性，特别是在感染率高的环境中。墨西哥排名 截至 11 月 3 日，就 COVID-19 负担而言，拉丁美洲排名第三，病例超过 700 万例， 2022 年，报告的 COVID-19 相关死亡总数位居全球第三，死亡人数超过 330,000。 COVID-19 大流行凸显了当前监测系统的缺陷 墨西哥。墨西哥 SARS-CoV-2 的基因组流行病学代表性不足， 由于病毒基因组的空间覆盖范围有限，其特征不足。之间的遗传差异 墨西哥、美洲和全球范围内流行的 SARS-CoV-2 病毒尚不清楚。墨西哥幅员辽阔 以及在人口结构、气候和人口流动性方面存在差异的多元化国家 2019 年美国游客数量达到 3240 万人次 5. 我们之前的工作 尤卡坦半岛的流感病毒显示出季节性和遗传性的有力证据 全国各地的变体差异很大，包括温带和热带地区 6,7。因此 检查墨西哥 SARS-CoV-2 的基因组流行病学，特别是在旅游密集的州 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 阐明随着疾病流行而发生的进化变化。由于之间的紧密联系 在墨西哥和美国，这些分析也将有助于为两国的公共卫生干预措施提供信息 国家。 该项目利用尤卡坦半岛和新近生成的 SARS-CoV-2 数据 因此在墨西哥，能够：1) 流行病学和数学模型来评估 疫苗接种运动背景下病毒传播和多样性的变化以及 人口流动性，并估计新变体在人口水平上的适应度优势，以及 2) 通过生成基因组序列和重建来表征循环变异 导致当地流行的物种出现或引入的进化历史和迁徙 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 墨西哥尤卡坦半岛缺乏数学建模。这项工作将建设当地能力 通过提供准确的信息来解决这些问题并对公共健康产生重大影响 有关 COVID-19 传播动态的信息。