Variant- and vaccination-specific alternative splicing profiles in SARS-CoV-2 infections

The COVID-19 pandemic, driven by the SARS-CoV-2 virus and its variants, highlights the important role of understanding host -viral molecular interactions influencing infection outcomes. Alternative splicing postinfection can impact both host responses and viral replication. We analyzed RNA splicing patterns in immune cells across various SARS-CoV-2 variants, considering immunization status. Using a dataset of 190 RNA-seq samples from our prior studies, we observed a substantial deactivation of alternative splicing and RNA splicing -related genes in COVID-19 patients. The alterations varied significantly depending on the infecting variant and immunization history. Notably, Alpha or Beta -infected patients differed from controls, while Omicron -infected patients displayed a splicing profile closer to controls. Particularly, vaccinated Omicron -infected individuals showed a distinct dynamic in alternative splicing patterns not widely shared among other groups. Our findings underscore the intricate interplay between SARS-CoV-2 variants, vaccination -induced immunity, and alternative splicing, emphasizing the need for further investigations to deepen understanding and guide therapeutic development.