Exploring the Replication and Pathogenic Characteristics of Alpha, Delta, and Omicron Variants of SARS-CoV-2

The variants of concern (VOCs) of SARS-CoV-2 have exhibited different phenotypic characteristics in clinical settings which are yet to be fully explored. This study aimed to characterize the viral replication features of major VOCs of SARS-CoV-2 and their association with pathogenicity. The Alpha, Delta, and Omicron variants of SARS-CoV-2 isolated from the COVID-19 patients in Japan were propagated in VeroE6/TMPRSS2 cells. The viral replication and pathological features were evaluated by laser and electron microscopy at different time points. The results revealed that the Delta variant dominantly infected the VeroE6/TMPRSS2 cells and formed increased syncytia compared to the Alpha and Omicron variants. Relatively large numbers of virions and increased immunoreactivities of the SARS-CoV-2 N-protein were detected in the endoplasmic reticulum and intracellular vesicles of Delta-infected cells. Interestingly, the N-protein and virions were detected in the nucleus of Delta-infected cells, while such properties were not observed in the case of Alpha and Omicron variants. In addition, early nuclear membrane damage followed by severe cellular damage was prominent in Delta-infected cells. A unique mutation (G215C) in the N-protein of the Delta variant is thought to be associated with severe cell damage. In conclusion, this study highlights the distinct replicative and pathogenic characteristics of the Delta variant of SARS-CoV-2 compared to the Alpha and Omicron variants, shedding light on the potential mechanisms underlying its increased pathogenicity.