Changes in NOS and ARG1 in AMN-SARS-CoV-2
Growing evidence suggests the roles of NOS and ARG1 in immune response modulation via arginine catabolism and the urea cycle[19, 20]. It has been shown that ARG1 activity is increased in COVID-19 patients and correlated with disease severity[21]. Consistently, our study revealed significantly increased ARG1 mRNA expression in the AMN-SARS-CoV-2 group (Figure 3A). It is well-established that elevated ARG1 competes with NOS for arginine, resulting in decreased NOS activity. Three distinct isoforms of NOS, neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS), regulate vascular health, with eNOS contributing to healthy blood flow by releasing nitric oxide, which effectively counteracts arterial tone[22]. Consequently, eNOS levels were significantly elevated in the AMN-SARS-CoV-2 group (Figure 3A). UHPLC-LC/MS analysis also identified the upregulation of ADMA (Figure 3B), a known endogenous NOS inhibitor. Increased ADMA could further contribute to NOS suppression. ROC analysis for ARG1, NOS, and ADMA yielded AUC values of 0.8571, 0.6837, and 0.7959, respectively (Figure 3C). Correlation analysis indicated that NOS was negatively correlated with ARG1 (r = -0.428) and ADMA (-0.469). However, NOS displayed no significant correlation with the metabolites ornithine, citrulline, and L-proline.