Poly(A) tail dynamics, non-adenine incorporation and alternative polyadenylation shape the host transcriptome in COVID-19 pathogenesis.

The COVID-19 pandemic has had a profound global impact since its emergence in late 2019. Characterized by a wide spectrum of clinical manifestations, COVID-19 has necessitated extensive research into the host-pathogen interactions that drive disease progression. Understanding the molecular mechanisms underlying the host response to SARS-CoV-2 infection is crucial for the development of effective therapeutic interventions and preventative strategies. This study employed a multi-omic approach that combined direct RNA sequencing (DRS) and Illumina cDNA sequencing to investigate whole blood transcriptomic profiles in COVID-19 patients. By leveraging the unique capabilities of Nanopore DRS, which provides long-read sequencing data, we were able to capture not only gene expression levels but also crucial poly(A) tail length fluctuations and non-adenine residue (non-A) modifications. This comprehensive analysis allowed us to identify differentially expressed genes and explore the impact of these poly(A) modifications on function within the context of COVID-19. Findings reveal significant alterations in gene expression patterns, poly(A) tail lengths and non-A modifications in COVID-19 patients compared to healthy controls. Results provide valuable insights into the complex interplay between viral infection, host immune response, and RNA processing, contributing to a deeper understanding of COVID-19 pathogenesis.