With the continuous emergence of highly transmissible SARS-CoV-2 variants, thecomparison of their infectivity has become a critical issue for public health. However,a direct assessment of the viral characteristic has been challenging becauseof the lack of appropriate experimental models and efficient methods. Here, weintegrated human alveolar organoids and single-cell transcriptome sequencing tofacilitate the evaluation. In a proof-of-concept study with four highly transmissibleSARS-CoV-2 variants, including GR (B.1.1.119), Alpha (B.1.1.7), Delta(B.1.617.2), and Omicron (BA.1), a rapid evaluation of the relative infectivitywas possible. Our system demonstrates that the Omicron variant is 5- to 7-foldmore infectious to human alveolar cells than the other SARS-CoV-2 variants atthe initial stage of infection. To our knowledge, for the first time, this study measuresthe relative infectivity of the Omicron variant under multiple virus co-infectionand provides new experimental procedures that can be applied to monitoremerging viral variants.