Objective  To understand the infection source of an outbreak of coronavirus disease 2019 (COVID-19) occurred in Zhenkang county, Yunnan province in September 2022 and analyze the variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

  Methods  The samples were collected from 9 local cases and 3 imported cases for whole-genome sequencing of SARS-CoV-2. The virus genome variation and the infection source were identified by the genomics analysis and epidemiological investigation.

  Results  The SARS-CoV-2 strains detected in 9 local cases belonged to Omicron BA.5.2 and BA.5.2.20, indicating two independent transmission chains. The genome sequences of the strains were highly homologous to the strains from 3 imported cases. The epidemiological investigation also indicted that the infections might be related to the direct or indirect contacts with the imported cases. The BA.5.2 and BA.5.20 strains shared 53 amino acid missense mutations and 11 amino acid deletion mutations, but each had its representative amino acid mutation site, respectively. HV69-70del, L452R, T478K, R493Q reversion, F486V and other vital mutation sites were found in the S protein of these SARS-CoV-2 strains, which might affect the transmission and immune escape of Omicron variant of SARS-CoV-2. The functional effects of the other characteristic mutations, such as S: K147T, S: M1237V, ORF1a: M85del were discovered in this study, for which further studies are needed.

  Conclusion  The epidemic might be associated with two imported infection sources, indicating the complexity and protracted nature of the epidemic in Yunnan border area. Therefore, the sensitivity of surveillance and forewarning still needs to be enhanced in border areas, and the dynamic surveillance for virus mutation should be continued to further improve the accuracy of the prevention and control of the epidemic.