Mutational analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can quantify the relative importance of variants over time, enable dominant mutations to be identified, and facilitate near real-time detection, comparison and tracking of evolving variants. SARS-CoV-2 in Asturias, an autonomous community of Spain with a large ageing population, and high levels of migration and tourism, was monitored and tracked from the beginning of the pandemic in February 2020 until its decline and stabilization in August 2021, and samples were characterized using whole genomic sequencing and single nucleotide polymorphisms. Data held in the GISAID database were analysed to establish patterns in the appearance and persistence of SARS-CoV-2 strains. Only 138 non-synonymous mutations occurring in more than 1 % of the population with SARS-CoV-2 were found, identifying ten major variants worldwide (seven arose before January 2021), 19 regional and one local. In Asturias only 17 different variants were found. After vaccination, no further regional major variants were found. Only half of the defined variants circulated and no new variants were generated, indicating that infection control measures such as rapid diagnosis, isolation and vaccination were efficient.