The exploration of glucocorticoid pathway based on disease severity in COVID-19 patients

Systemic inflammation is a hallmark of Coronavirus Disease 2019 (COVID-19) and is the key to the pathophysiology of its severe cases with host cytokine involvement. Glucocorticoids can moderate this inflammatory effect due to receptor binding (NRC31-the gene encoded), influencing the expression of effector genes and pro-inflammatory cytokines. Another important pathway in the processes of the immune and inflammatory responses is nuclear factor-κB (NF-κB) signaling (NFKBIA-the gene encoded). We aimed to explore the expression of genes in the glucocorticoid pathway in mild and severe COVID-19. We performed a cross-sectional, observational study on COVID-19 cases, assessing the expression of RNA in white blood cells. The Illumina® platform was used for RNA sequencing, and FASTQ data were quality-checked with Multiqc. The raw data were analyzed using CLC Genomics Workbench®. Our study included 23 patients with severe COVID-19 and 21 patients with mild COVID-19 with an average age of 49.9 ± 18.2 years old. The NR3C1 and NFKBIA expressions did not show a significantly significant difference between groups (log2 fold change 0.5, p = 0.1; 0.82, p = 0.09). However, the expressions of TSC22D3, DUSP-1, JAK-1 and MAPK-1 were significantly higher in mild cases (log2 fold change 1.3, p < 0.001; 2.6, p < 0.001; 0.9, p < 0.001; 1.48, p-value<0.001; respectively). Furthermore, the TNF, IL-1β, and IL-6 expressions were significantly lower in mild cases (log2 fold change 4.05, p < 0.001; 3.33, p < 0.001; 6.86, p < 0.001; respectively). In conclusion, our results showed that although the NRC31 and NFKBIA expressions did not show a statistically significant difference between groups, the expression of TSC22D3 was higher in mild cases. These results highlight the importance of effector genes, specifically TSC22D3, in combatting systemic inflammation. Our recent findings have the potential to lead to the identification of novel pharmacological targets that could prove to be vital in the fight against diseases associated with inflammation.