LAUSR

The COVID‐19 pandemic has resulted in the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, including the Mu variant (B.1.621), first identified in Colombia in January 2021. This variant exhibits a distinct mutational profile, predominantly in the spike protein region which impact the virus's ability to be recognized by antibodies from natural infection or vaccination. Mu variant has been highly prevalent in Colombia, (https://outbreak.info/ location-reports?loc=VEN%26alias=Mu%26dark=true%26selected=Mu) and associated with a significant number of COVID‐19‐related deaths. Investigations into its emergence and spread have been conducted in various Colombian departments and neighboring countries, including Venezuela, where it was introduced through population displacement via the frontier with Colombia. Despite the well‐ known spread and dispersion of SARS‐CoV‐2 among both countries, few studies have assessed the epidemiological impact, genomic features, and phylogenetic relationship of the Mu variant in Colombian departments bordering the Western Venezuelan states with the highest prevalence of COVID‐19 cases. This data is of utmost importance, particularly in context of the ongoing Venezuelan humanitarian and refugee crisis. Twenty‐four SARS‐CoV‐2 positive samples collected between May 2021 and February 2022 were analyzed, with16 and 8 from Colombian and Venezuelan patients respectively. Whole genome analysis and lineage identification were performed as previously reported. The sociodemographic characteristics of patients are included in Supporting Information: Table 1. Comparative genomics analysis was conducted to assess phylogenomic relationships of 24 genomes, these were compared against 18 111 Colombian genomes, 542 Venezuelan genomes and 2365 reference genomes (representative selection of all SARS‐CoV‐2 lineages). The 21 042 genomes were aligned and used to build a maximum likelihood tree following a previously published pipeline. A single‐nucleotide polymorphism analysis was performed to compare Mu variant from this current study with other Colombian‐Venezuelan Mu variants. Relevant variables were analyzed using descriptive statistics. Shapiro‐Wilk Test was used to normality evaluation following by non‐parametric Kruskal−Wallis test. For categorical variables, χ2 and post hoc for multiple comparisons were used. The Mu variant was the most commonly identified infecting‐ lineage, this variant was found in 83.3% of cases, followed by BA.1.1 and B.1.625 (Supporting Information: Table 1). Most patients were female from Cucuta, with a mean age of 41.1 years. There were no statistically significant differences in Ct values between lineages and there was no relationship between specific lineages and country of birth. Mu variants from this study showed closer relation to Venezuelan Mu variants than Colombian Mu variants (Figure 1A). We identified 32 polymorphic sites that distinguished the 20 Mu variants recognized in this study in contrast to the Wuhan reference sequence. The comparative analysis between the 20 Mu variants from Norte de Santander and those Mu variants from Venezuela and Colombia revealed 24 shared nonsynonymous substitutions (NSS) (Figure 1B). Unique NSS were identified in each group assessed. L18F and M1237I mutations were identified in 13% of the Mu variants from Venezuelan genomes. This study explores the epidemiological and genomic characteristics of the Mu variant in Norte de Santander, a Colombian department bordering Venezuela, which has a high number of natural infections and deaths from SARS‐CoV‐2, as well as a large number of refugees and migrants from Venezuela (source: https://data.unhcr. org/en/country/col). Results revealed that the Mu variant caused most COVID‐19 cases (83.3%) in Norte de Santander between May 2021 and February 2022, which is consistent with the epidemiological report for the Venezuelan border states with the highest number of COVID‐19 cases, (source: https://www.mincyt.gob.ve/wp-content/uploads/2022/02/ReporteMarzo-2021-Enero-2022-Variantes-y-Linajes-SARS-Cov-2-VenezuelaVigilancia-Genomica-1-1.pdf. A close phylogenetic relationship was observed between Mu variants from this study and Venezuelan Mu variants (Figure 1A), as well as a high similarity at the level of polymorphisms (Figure 1B). These findings support the hypothesis of introduction of the Mu‐ variant from Colombia to Venezuela and subsequent spread, which is particularly relevant in light of the current socioeconomic and political conditions, as well as the ongoing health emergency, that continues to promote the migration of the Venezuelan population to bordering countries. Migration could facilitate the exchange, introduction, and spread of SARS‐CoV‐2 variants, including high‐impact ones with significant immune escape abilities. In addition, this study identified two NSS in Mu variants from Venezuela (L18F and M1237I) which confer replicative advantage and mAb escape. These mutations, present in 13% of the variants, have clinical and epidemiological importance and may affect diagnosis and treatment. Further genomic surveillance is needed. One limitation of this study was the small number of available genomes from Norte de Santander and neighboring states in Venezuela, which may result in sample bias. Therefore, closer