Neuropilin-1 (NRP1) and ACE2 synergy in immune cells: a key determinant of disease severity in COVID-19

The progression from mild to severe COVID-19 is associated with dysregulated host immune responses, although the underlying molecular mechanisms in immune cells remain incompletely characterized. Here, we investigated the association of ACE2 and Neuropilin-1 (NRP1) expression in peripheral blood mononuclear cells (PBMCs) with COVID-19 severity. In an analytical cross-sectional study, 40 patients with COVID-19 (20 milds and 20 severe) and 40 healthy controls were evaluated. Expression of ACE2, NRP1, and apoptosis-related genes in PBMCs was assessed by quantitative real-time PCR, while serum IL-6 and biochemical markers were evaluated. ACE2 expression was significantly increased in severe COVID-19 patients, accompanied by elevated NRP1 expression and a strong positive correlation between the two markers. BCL-2 expression showed a downward trend in severe cases, although this difference did not reach statistical significance. Serum IL-6 and CK levels were significantly higher in severe patients than in healthy controls ( p = 0.010 and p = 0.030, respectively), whereas LDH, ALT, and AST did not differ significantly between these groups. These findings indicate that increased ACE2 and NRP1 expression in PBMCs is associated with severe COVID-19 and may contribute to immune dysregulation. Further longitudinal and functional studies are required to determine the prognostic and therapeutic relevance of these molecular changes.