SARS-CoV-2 BW.1, a fast-growing Omicron variant from southeast Mexico bearing relevant escape mutations (preprint)

Purpose The swift growth of the BW.1 SARS-CoV-2 variant coincides with a new rapid increase of COVID-19 cases occurring in Southeast Mexico in October, 2022, putting an end to a period of low transmission after Mexico’s fifth epidemiological wave. Up to 75% of weekly sequenced genomes in the region have been identified as BW.1. In the current study, a comprehensive genomic comparison was carried out to characterize BW.1’s evolutionary history, identifying its origins and its most important mutations.Methods An alignment of all the genomes of BW.1 and its parental BA.5.6.2 variant was carried out to identify their mutations. A phylogenetic reconstruction and a longitudinal analysis of point mutations were performed to trace back their origin and contrast them with key RBD mutations in variant BQ.1, one of the fastest growing lineages to date.Results The BW.1’s genome derives from Mexican sequences of BA.5.6.2. Two traceable synonymous substitutions support its Mexican origin whereas other two are specific to BW.1: S:N460K and ORF1a:V627I. Mutations found in the receptor binding domain, S:K444T, S:L452R, S:N460K and S:F486V, in BW.1 have been reported to be relevant for immune escape and are key mutations in the BQ.1 lineage.Conclusions BW.1 appears to have arisen in the Yucatan Peninsula in Mexico sometime around July 2022 during the fifth COVID-19 wave. Its explosive growth may be in part explained by relevant escape mutations also found in BQ.1.

Regional epidemic dynamics and Delta variant diversity resulted in varying rates of spread of Omicron-BA.1 in Mexico (preprint)

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),

Overview of the SARS-CoV-2 genotypes circulating in Latin America during 2021 (preprint)

Latin America is one of the regions in which the COVID-19 pandemic has had a stronger impact, with more than 72 million reported infections and 1.6 million deaths until June 2022. Since this region is ecologically diverse and is affected by enormous social inequalities, efforts to identify genomic patterns of the circulating SARS-CoV-2 genotypes are necessary for the suitable management of the pandemic. To contribute to the genomic surveillance of the SARS-CoV-2 in Latin America, we extended the number of SARS-CoV-2 genomes available from the region by sequencing and analyzing the viral genome from COVID-19 patients from seven countries (Argentina, Brazil, Costa Rica, Colombia, Mexico, Bolivia and Peru). Subsequently, we analyzed the genomes circulating mainly during 2021 including records from GISAID database from Latin America. A total of 1534 genome sequences were generated from seven countries, demonstrating the laboratory and bioinformatics capabilities for genomic surveillance of pathogens that have been developed locally. For Latin America, patterns regarding several variants associated with multiple re-introductions, a relatively low percentage of sequenced samples, as well as an increment in the mutation frequency since the beginning of the pandemic, are in line with worldwide data. Besides, some variants of concern (VOC) and variants of interest (VOI) such as Gamma, Mu and Lambda, and at least 83 other lineages have predominated locally with a country-specific enrichments. This work has contributed to the understanding of the dynamics of the pandemic in Latin America as part of the local and international efforts to achieve timely genomic surveillance of SARS-CoV-2.

Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico (preprint)

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.

Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico (preprint)

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.

Dominance of Three Sublineages of the SARS-CoV-2 Delta Variant in Mexico (preprint)

In this study, we analyzed sequences of SARS-CoV-2 isolates of the Delta variant in Mexico, which completely replaced other previously circulating variants in the country due to its transmission advantage. Among Delta sublineages detected, 81.5 % were classified as AY.20, AY.26, and AY.100. According to publicly available data, these sublineages only reached a world prevalence of less than 1%, suggesting a possible Mexican origin. The signature mutations of these sublineages are described, and phylogenetic analyses and haplotype networks were used to track their spread across the country. Other frequently detected sublineages include AY.3, AY.62, AY.103, and AY.113. Over time, the principal sublineages showed different geographical distributions, with AY.20 predominant in Central Mexico, AY.26 in the North, and AY.100 in the Northwest and South/Southeast. This work describes the circulation, from May to November 2021, of the primary sublineages of the Delta variants associated to the third wave of the COVID-19 pandemic in Mexico and reinforces the importance of SARS-CoV-2 genomic surveillance for timely identification of emerging variants that may impact public health.

Emergence and spread of the potential variant of interest (VOI) B.1.1.519 predominantly present in Mexico. (preprint)

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.

Seroprevalence and Neutralizing Activity of IgG Antibodies Against SARS-CoV-2 in Mexico (preprint)

Background: Until recently, the incidence of COVID-19 was primarily estimated using molecular diagnostic methods. However, it is internationally accepted that the number of cases is vastly underreported using these methods. Antibody prevalence studies estimate cumulative infection incidences and allow monitoring of transmission dynamics, and the presence of neutralizing antibodies in the population.Methods: In February 2020, the Mexican Social Security Institute began conducting anonymous unrelated sampling of residual sera from specimens collected in clinical laboratories and blood banks across all 32 of the country’s states. Sampling was carried out weekly and began 17 days before Mexico’s first officially confirmed case. The 14,515 sera obtained were analyzed by chemiluminescent-linked immunosorbent assay (CLIA) IgG S1/S2 to determine the presence of total IgG antibodies and, later, positive cases using this technique were also analyzed to determine the rate of neutralization using the enzyme-linked immunosorbent assay (ELISA).Findings: We identified 40 CLIA IgG positive cases before the first official report of SARS-CoV-2 infection in Mexico. The national seroprevalence was 3∙5% in February and 21∙7% in August. Neutralizing activity among patients who generate IgG antibodies was 87∙9% in August 2020 and 10∙4% during the overall study period.Interpretation: The actual extent of the SARS-CoV-2 infection in Mexico is 21 times higher than that reported by molecular techniques. Although the general population is still far from achieving herd immunity, epidemiological indicators of disease burden, and fatality should be re-estimated based on serological studies of this type.Funding Statement: National Council of Science and Technology (CONACyT).Declaration of Interests: The authors have no conflicts of interests to declare.Ethics Approval Statement: This protocol was approved by the scientific, ethics, and biosafety committees of the IMSS National Scientific Research Commission (R-785-2020-60).

Weak association of coinfection by SARS-CoV-2 and other respiratory viruses with severe cases and death (preprint)

SARS-CoV-2 is a novel coronavirus described for the first time in China in December 2019. This virus can cause a disease that ranges in spectrum from asymptomatic to severe respiratory disease with multiorgan failure, and the most severe cases are associated with some comorbidities and patient age. However, there are patients who do not have those risk factors who still develop serious disease. In this study, we identified the presence of other respiratory viruses in positive cases of COVID-19 in Mexico to determine if any coinfections were correlated with more severe manifestations of COVID-19. We analysed 103 confirmed cases of COVID-19 using RT-qPCR for the detection of 16 other respiratory viruses.Of the cases analysed, 14 (13.6%) were cases of coinfection, and 92% of them never required hospitalization, even when comorbidities and advanced age were involved. There were not significant differences between the presence of comorbidities and the mean ages of the groups. These results suggest that coinfection is not related to more severe COVID-19 and that, depending on the virus involved, it could even lead to a better prognosis. We believe that our findings may lay the groundwork for new studies aimed at determining the biological mechanism by which this phenomenon occurs and for proposing corresponding strategies to limit the progression to severe cases of COVID-19.

Genomic analysis of early SARS-CoV-2 strains introduced in Mexico (preprint)

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.