Deciphering the Host-Pathogen Interface in COVID-19: The precision molecular insight into epitranscriptomic modifications of high-impact transcripts

Abstract

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact since its emergence in late 2019. Characterized by a wide spectrum of clinical manifestations, ranging from asymptomatic infection to severe respiratory distress and death, 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 RNA modifications, including poly(A) tail length, non-adenine residue (non-A), pseudouridylation (psU), and 5-methylcytosine (m5C) methylation. This comprehensive analysis allowed us to identify differentially expressed genes (DEGs) and explore the impact of these RNA modifications on gene expression and function within the context of COVID-19. Our findings reveal significant alterations in gene expression patterns, poly(A) tail lengths, non-A and the prevalence of psU and m5C modifications in COVID-19 patients compared to healthy controls. These 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.