Dynamics of gene expression profiling by RNA-Seq and identification of high-risk patients for severe COVID-19 [RNA-Seq]

The clinical manifestations of SARS-Co-2 infection vary widely, from asymptomatic infection to the development of acute respiratory distress syndrome (ARDS) and death. The host response elicited by SARS-CoV-2 plays a key role in determining the clinical outcome. We hypothesized that determining the dynamic whole blood transcriptomic profile of adult patients hospitalized for COVID-19 and characterizing the subgroup that develops severe disease and ARDS would broaden our understanding of the heterogeneity in clinical outcomes. We recruited 60 hospitalized patients with microbiology-confirmed COVID-19, among whom 19 developed ARDS. Peripheral blood was collected using PAXGene RNA tubes within 24 hours of admission and at day 7. There were 2150 differently expressed genes in patients with ARDS at baseline, and 1963 at day 7. We found a dysregulated inflammatory response in COVID-19 ARDS patients, with an increased expression of genes related to pro-inflammatory molecules and neutrophil and macrophage activation at admission, in addition to the loss of immune regulation. This led in turn to a higher expression of genes related to reactive oxygen species, protein polyubiquitination, and metalloproteinases in latter stages. Some of the most significant differences in gene expression found between patients with and without ARDS corresponded to long non-coding RNA involved in epigenetic control.