Relative infectivity of the SARS-CoV-2 Omicron variant in human alveolar cells (preprint)

With the emergence of multiple highly transmissible SARS-CoV-2 variants during the recent pandemic, the comparison of their infectivity has become a substantially critical issue for public health. However, a direct assessment of these viral characteristics has been challenging due to the lack of appropriate experimental models and efficient methods. Here, we integrated human alveolar organoids and single-cell transcriptome sequencing techniques to facilitate the evaluation. In a proof-of-concept study using the assay with four highly transmissible SARS-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 infectivity was possible. Our results demonstrate that the Omicron (BA.1) variant is 3-5-fold more infectious to human alveolar cells than the other SARS-CoV-2 variants at the early phase of infection. To our knowledge, this study provides the first direct measurement of the infectivity of the Omicron variant and new experimental procedures that can be applied for monitoring newly emerging viral variants.

Robust three-dimensional expansion of human adult alveolar stem cells and SARS-CoV-2 infection (preprint)

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which is the cause of a present global pandemic, infects human lung alveolar cells (hACs). Characterising the pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hACs limits the study. Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for human alveolar type 2 (hAT2) cells, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2, and the application of long-term 3D hAT2 cultures as models for respiratory diseases.