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The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In Mexico, this subvariant began spreading during the first week of December 2021 and became dominant in the next three weeks, causing the fourth COVID-19 epidemiological surge in the country. Unlike previous SARS-CoV-2 variants, BA.1 did not acquire local substitutions nor exhibited a geographically distinct circulation pattern in Mexico. However, a regional difference in the speed of the replacement of the Delta variant was observed, as some northern states showed persistence of Delta lineages well into February 2022. Mexican states were divided into four regions (North, Central North, Central South, and Southeast) based on the lineage circulation before the dominance of BA.1 to study possible causes for this difference. For each region, the time to fixation of BA.1, the diversity of Delta sublineages in the weeks preceding BA.1 entry, the population density, and the level of virus circulation during the inter-wave interval were determined. An association between a faster Omicron spread and lower Delta diversity, as well as fewer COVID-19 cases during the Delta-BA.1.x inter-wave period, was observed. For example, the North region exhibited the slowest spread but had the highest diversity of Delta sublineages and the greatest number of inter-wave cases relative to the maximum amount of the virus circulating in the region, whereas the Southeast region showed the opposite. Viral diversity and the relative abundance of the virus in a particular area around the time of the introduction of a new lineage seem to have influenced the spread dynamics. Nonetheless, if there is a significant difference in the fitness of the variants or the time allowed for the competition is sufficient, it seems the fitter virus will eventually become dominant, as observed in the eventual dominance of the BA.1.x variant in Mexico. Impact statementThe surveillance of lineage circulation of SARS-CoV-2 has helped identify variants that have a transmission advantage and are of concern to public health and to track the virus dispersion accurately. However, many factors contributing to differences in lineage spread dynamics beyond the acquisition of specific mutations remain poorly understood. In this work, a description of BA.1 entry and dispersion within Mexico is presented, and which factors potentially affected the spread rates of the Omicron variant BA.1 among geographical regions in the country are analyzed, underlining the importance of population density, the proportion of active cases, and viral lineage diversity and identity before the entry of BA.1. Data summaryThis work was carried out using data shared through the GISAID initiative. All sequences and metadate are available through GISAID with the accession EPI_SET_220927gw, accession numbers and metadata are also reported in the supplemental material of this article. Epidemiological data was obtained though the Secretaria de Salud website (https://www.gob.mx/salud/documentos/datos-abiertos-152127),
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Up to November 2021, over 200 different SARS-CoV-2 lineages circulated in Mexico. To investigate lineage replacement dynamics, we applied a phylodynamic approach to explore the evolutionary trajectories of five dominant lineages that circulated during the first year of the local epidemic. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in the country. Lineages B.1.1.222 and B.1.1.519 showed comparable dynamics, represented by clades likely originating in Mexico and persisting for over a year. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. We further explored viral movements across the country, applied within the largest clades identified (belonging to lineage B.1.617.2). Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.
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SARS-CoV-2 variants have emerged in late 2020 and there are at least three variants of concern (B.1.1.7, B.1.351, P1) reported by WHO. These variants have several substitutions in the Spike protein that affect receptor binding; they present increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we are reporting the identification of a potential variant of interest harboring the mutations T478K, P681H, and T732A in the Spike protein, within the newly named lineage B.1.1.519, which rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021.
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Understanding the evolution of SARS-CoV-2 virus in various regions of the world during the Covid19 pandemic is essential to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A RT-qPCR screening and phylogenomics reconstructions directed a sequence/structure analysis of the Spike glycoprotein, revealing mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show Spike protein mutations in the N-terminal domain (i.e., R190M), in the receptor-binding motif (i.e., T478K, E484K), within the S1-S2 subdomains (i.e., P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the variants of interest (VOI) we postulate: 20B/478K.V1 (B.1.1.222 or B.1.1.519) and 20B/P.4 (B.1.1.28.4). Moreover, the population patterns of Single Nucleotide Variants (SNVs) from symptomatic and asymptomatic carriers obtained with a self-sampling scheme confirmed the presence of several fixed variants, and differences in allelic frequencies among localities. We identified the mutation N:S194L of the Nucleocapsid protein associated with symptomatic patients. Phylogenetically, this mutation is frequent in Mexican sub-clades, so we propose an additional VOI, 20A/N:194L.V2 (B.1.243). Our results highlight the dual and complementary role of Spike and Nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage. IMPACT STATEMENTFollowing self-sampling, screening of mutations of concern, and a combined phylogenomic and population genetics pipeline, we reveal the appearance of three VOI with mutations in the Spike protein, P.4 (B.1.1.28.4) and 20B/478K.V1 (B.1.1.222, leading to B.1.1.519), and in the Nucleocapsid protein, 20A/N:194L.V2 (B.1.243), in Mexico during the pre-vaccination stage. The mutation S194L in the Nucleocapsid was found to associate with symptomatic patients versus asymptomatic carriers in the population investigated. Our research can aid epidemiological genomics efforts during the vaccination stage in Mexico by contributing with a combined analytical platform and information about variants within different genetic lineages with the potential to evolve into variants of concern (VOC).
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The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described in the country. Within this Mexican cluster, we also identified an H49Y amino acid change in the spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts. This work is the result of the collaboration of five institutions into one research consortium: three public health institutes and two universities. From the beginning of this work, it was agreed that the experimental leader of each institution would share the first authorship. Those were the criteria followed to assign first co-first authorship in this manuscript. The order of the other authors was randomly assigned. IMPORTANCEUnderstanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.
