Role of CXCL12/CXCR4 pathway and miRNA expression profiles on polymorphonuclear mobilization in COVID-19 patients

Introduction: Polymorphonuclear neutrophils (PMN) are actively recruited during COVID-19 and yet dysfunctions are associated with its prognosis. The PMN receptor CXCR4 and its ligand SDF-1/CXCL12 are known to play a role in the recruitment of PMN. The primary objective was to evaluate the modulation of this pathway in COVID-19 patients and after treatment with dexamethasone (DXM). Secondary objectives were to evaluate miRNA expression profiles. Material and Methods We conducted a prospective study comparing patients admitted to the emergency department from December 2022 to April 2023 for SARS-CoV-2 infection with a control population. We studied the PMN surface expression of the CXCR4 receptor, circulating levels of SDF-1 and miR levels. Patients treated with dexamethasone (DXM) were sampled again at H48. Results Forty-four infected patients and 20 controls were analyzed. SDF-1 levels were significantly increased in COVID-19 patients and significantly decreased after treatment by DXM and CXCR4 + PMN percentages increased significantly. SDF-1 levels on admission were associated with the risk of mechanical ventilation. Levels of miR 15b-5p, miR 146a-5p, miR 155-5p and miR 30d-5p were significantly increased in COVID-19 patients. Levels of miR-hsa-122 on admission were found significantly associated with mortality and its variation with the need for mechanical ventilation. Conclusions Our study suggests a possible involvement of the SDF-1/CXCR4 axis in the physiopathogenesis of COVID-19.