Preliminary miRNA profiling of plasma from patients infected with distinct SARS-CoV-2 variants.

BACKGROUND: Epigenetic regulation can play a dual role in viral infection, acting as part of the host defense, while being hijacked to control viral latency, replication, and persistence. During the COVID-19 pandemic, substantial evidence indicated that different SARS-CoV-2 variants may lead to distinct outcomes by affecting different molecular pathways, including epigenetic mechanisms. METHODS AND RESULTS: In this study, we assessed miRNA expression using high-throughput microarray technology to simultaneously measure the expression of thousands of miRNAs. We focused on: comparing Delta and Omicron infections with healthy controls; identifying specific miRNAs linked to symptom severity; analyzing miRNA expression across different stages of Delta variant infection; and predicting miRNA target genes and evaluating miRNA-mRNA interactions. We identified 65 miRNAs that were significantly differentially expressed simultaneously in both SARS-CoV-2 variants compared to healthy samples. These miRNAs were categorized into distinct functional groups based on their roles in viral infection. We observed an association between the expression of specific miRNAs and virus-induced symptom severity and patients' outcomes in both variants. Furthermore, we examined miRNA expression across the various phases of the Delta variant and identified 38 miRNAs that were significantly differentially expressed. Finally, mRNA-miRNA interaction analysis revealed PTEN, IGF1R, MYC, and STAT3 as the most interacting genes. CONCLUSION: Profiling thousands of miRNAs in response to different SARS-CoV-2 variants offers new opportunities for diagnosis, prognosis, and therapy. Although comorbidities and pathway cross-talk may influence the obtained results, our findings provide novel insights into the host response to SARS-CoV-2 infection at the epigenetic level.