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

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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.