Dynamics of Gene Expression Profiling and Identification of High-Risk Patients for Severe COVID-19.

The clinical manifestations of SARS-CoV-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 hospitalized adult COVID-19 patients 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 RT-PCR-confirmed SARS-CoV-2 infection, among whom 19 developed ARDS. Peripheral blood was collected using PAXGene RNA tubes within 24 h of admission and on day 7. There were 2572 differently expressed genes in patients with ARDS at baseline and 1149 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 an immune regulation loss. This led, in turn, to a higher expression of genes related to reactive oxygen species, protein polyubiquitination, and metalloproteinases in the 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.

Circulating microRNA profiling is altered in the acute respiratory distress syndrome related to SARS-CoV-2 infection.

One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Circulating miRNAs in patients who underwent ARDS and needed mechanical ventilation (MV+; n = 15) were analyzed by next generation sequencing in comparison with patients who had COVID-19 poor symptoms but without intensive care unit requirement (MV-; n = 13). A comprehensive in silico analysis by integration with public gene expression dataset and pathway enrichment was performed. Whole miRNA sequencing identified 170 differentially expressed miRNAs between patient groups. After the validation step by qPCR in an independent sample set (MV+ = 10 vs. MV- = 10), the miR-369-3p was found significantly decreased in MV+ patients (Fold change - 2.7). After integrating with gene expression results from COVID-19 patients, the most significant GO enriched pathways were acute inflammatory response, regulation of transmembrane receptor protein Ser/Thr, fat cell differentiation, and regulation of biomineralization and ossification. In conclusion, miR-369-3p was altered in patients with mechanical ventilation requirement in comparison with COVID-19 patients without this requirement. This miRNA is involved in inflammatory response which it can be considered as a prognosis factor for ARDS in COVID-19 patients.