Researchers continue to uncover how SARS-CoV-2, the virus responsible for COVID-19, has changed over time to better understand how it affects the human body. Researchers at Wake Forest University School of Medicine used RNA sequencing to examine how different variants of the virus influence gene expression in infected individuals.

The team analyzed RNA sequencing data from blood samples of people infected with multiple SARS-CoV-2 variants, including the Original Wuhan, French, Beta, and Omicron variants. They compared these samples to those from healthy individuals to identify which genes were turned on or off during infection. Early variants were found to interfere with pathways related to viral replication. In contrast, later variants like Beta and Omicron were more focused on manipulating the immune system to avoid detection and destruction.

Using sophisticated statistical methods and machine learning, the researchers identified a set of genes that could accurately detect COVID-19 infection regardless of the variant. Some of the most reliable gene markers included IFI27, CDC20, and RRM2. When tested on separate datasets, these markers achieved remarkably high classification accuracy—over 97% in most cases and even 100% in some.

This figure depicts the analysis process employed in this study, starting from the use of RNA-Seq datasets to analyze gene expression dynamics across multiple SARS-CoV-2 variants, including the original Wuhan, severe hospitalized French cases, severe Beta cases, and moderate Omicron cases. The workflow incorporates GLMQL-MAS technique to identify differences in gene expression and pathway analyses, which aims to provide insights into the virus’s evolution and molecular differences. The second phase involves identifying common significant gene signatures across all variants using Cross-MAS and assessing these genes’ potential as signatures via principal component analysis and linear classifiers.

This research shows the power of RNA sequencing not only in tracking how the virus evolves, but also in developing flexible and accurate diagnostic tools that can adapt to new variants. It also highlights how our immune system’s interaction with SARS-CoV-2 changes as the virus continues to evolve.