What is known about this topic?: The emerging H5Ny lineages of the avian influenza virus (AIV) with genomic reassortments have posed a continuous threat to animals and human beings. Since the first case of avian influenza A (H5N6) virus infection in 2014, the World Health Organization has reported a total of 38 cases by August 6, 2021.

What is added by this report?: A total of 5 new cases of H5N6 that occurred from May 2021 to July 2021 in Sichuan Province, China were reported in this study. Epidemiological and laboratory information of the five cases were investigated. The genomic analysis of the H5N6 genomes showed the features of AIV genomic reassortments and key residue substitutions.

What are the implications for public health practice?: The emergence of human cases infected by AIV H5Ny lineages through time demonstrates a risk of the persistence and evolution of the virus to trigger sporadic outbreaks and even pandemics, which need continuous surveillance.