The relationship of soluble neuropilin-1 to severe COVID-19 risk factors in polycystic ovary syndrome

The SARS-CoV-2 coronavirus enters target cells via the angiotensin-converting enzyme 2 (ACE2) receptor; however, ACE2 expression does not match SARS-CoV-2 tissue load, suggesting additional co-factors are required for viral entry. Neuropilin-1 (NRP1) is such a co-factor that, when expressed alone shows minimal viral infectivity, but when co-expressed with ACE2 markedly increases viral infectivity. NRP1 is a transmembrane glycoprotein, which is expressed in endothelial cells, and serves as a receptor for vascular endothelial growth factor (VEGF), and both NRP1 and VEGF expression are increased in COVID-19 patients. SARS-CoV-2 uses the viral spike protein for cell entry, cleaving the protein that then attaches to NRP1. Therefore, tissues enriched for NRP1 have increased infectivity risk and subjects expressing increased NRP1 may have increased risk.