Objective To understand the genomic characteristics of the novel coronavirus (SARS-CoV-2) in Guizhou province from 2020 to 2023, to clarify the patterns of gene mutation, and the changes in susceptibility caused by key amino acid loci mutations.

Methods A total of 316 SARS-CoV-2 positive oropharyngeal and nasopharyngeal swab samples were collected in Guizhou province from 2020 to 2023. Whole-genome amplification and sequencing of the virus were performed using high-throughput sequencing technology. The off-machine data were analyzed using the Nextclade online data analysis platform to determine the virus types and evolutionary branches, as well as to analyze the variations of the key amino acid sites and the genetic evolution characteristics.

Results A total of 259 SARS-CoV-2 whole-genome sequences were successfully obtained, comprising 59 evolutionary branches. In the early stage (January to August 2020), the virus evolved to a limited extent, mainly consisting of the original strains (Pango lineage B.1). The second stage (September 2020 to December 2021) was dominated by the Delta variant (3 evolutionary branches), with 36 – 39 amino acid mutations, about 8 – 10 of which were spike protein mutation sites. The third stage (January 2022 to December 2023) was mainly dominated by the Omicron variant (56 evolutionary branches), with approximately 47 – 66 amino acid mutations, about 28 – 42 of which were spike protein mutation sites. The top three proportions were: the Omicron XBB recombinant and its sub-branches, Omicron BA.5.2 and its sub-branches, and Omicron BF.7 variants.

Conclusion The mutations occurring in the early stages of SARS-CoV-2 infections in Guizhou province from 2020 to 2023 exhibited a higher affinity for angiotensin-converting enzyme 2 (ACE2) binding and partial immune escape capability. Later mutations showed higher immune escape capability, leading to a gradually increasing immunological gap in the entire population.