In Mexico, the BA.4 and BA.5 Omicron variants dominated the fifth epidemic wave (summer 2022), superseding BA.2, which had circulated during the inter-wave period. The present study uses genome sequencing and statistical and phylogenetic analyses to examine these variants’ prevalence, distribution, and genetic diversity in Mexico from April to August 2022. Over 35% of the sequenced genomes in this period corresponded to the BA.2 variant, 8% to the BA.4, and 56% to the BA.5 variant. Multiple subvariants were identified, but only BA.2.9, BA.2.12.1, BA.5.1, BA.5.2, BA.5.2.1, and BA.4.1 circulated throughout the fifth wave across the entire country, not forming geographical clusters. Contrastingly, other subvariants exhibited a geographically restricted distribution, most notably in the Southeast region, which showed a distinct subvariant dynamic. This study supports previous results showing that this region may be a major entry point and may have contributed to the introduction and evolution of novel variants in Mexico. Furthermore, a differential distribution was observed for certain subvariants among specific States throughout time, which may have contributed to the overall increased diversity observed during this wave compared to the previous one. This study highlights the importance of sustaining genomic surveillance to identify novel variants that may impact public health.

Concerns about the prospect of a global pandemic have been triggered many times during the last two decades. These have been realized through the current COVID-19 pandemic, due to a new coronavirus SARS-CoV2, which has impacted almost every country on Earth. Here, we show how considering the pandemic through the lenses of the evolutionary ecology of pathogens can help better understand the root causes and devise solutions to prevent the emergence of future pandemics. We call for better integration of these approaches into transdisciplinary research and invite scientists working on the evolutionary ecology of pathogens to contribute to a more “solution-oriented” agenda with practical applications, emulating similar movements in the field of economics in recent decades.