Paradoxical Upregulation of miR-146a-5p and COX-2 in Peripheral Blood Mononuclear Cells is Associated with COVID-19 Disease Severity.

INTRODUCTION: COVID-19 is closely associated with inflammatory responses, highlighting the importance of investigating key regulatory pathways. Cyclooxygenase-2 (COX-2) and microRNA-146a-5p (miR-146a-5p) are important modulators of inflammation. This study aimed to evaluate their expression in Peripheral Blood Mononuclear Cells (PBMCs) of COVID- 19 patients and examine associations with disease severity compared with healthy controls. METHODS: This case-control study included 148 participants categorized by disease severity: 72 ICU-admitted patients, 41 severe cases, 15 outpatients, and 20 healthy controls. COX-2 and miR-146a-5p expression levels in PBMCs were measured using quantitative real-time PCR, and clinical and laboratory data were analyzed. RESULTS: COX-2 and miR-146a-5p expression levels were significantly elevated in ICUadmitted and severe patients compared with controls (p < 0.001). A moderate positive correlation was observed between miR-146a-5p and COX-2 expression (r = 0.584, p < 0.0001). The ICU group had a significantly higher mean age than other groups (p < 0.0001), and C-reactive protein levels increased significantly with disease severity (p < 0.0001). DISCUSSION: Increased expression of both markers was positively associated with disease severity, suggesting a complex inflammatory response. Unlike other inflammatory conditions where miR-146a-5p negatively regulates COX-2, both markers increased concurrently, possibly reflecting a compensatory response to heightened inflammation. However, the unequal distribution of sample sizes across study groups should be considered when interpreting the findings. CONCLUSION: COX-2 and miR-146a-5p expression levels were elevated in severe COVID-19 and positively correlated with disease severity. Their concurrent upregulation suggests involvement in inflammatory dysregulation and highlights their potential as biomarkers or therapeutic targets, warranting further investigation.