Effects of L-Arginine Plus Vitamin C Supplementation on L-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial

Altered L-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of L-arginine, citrulline, ornithine, monomethyl-L-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of L-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV2-infection. L-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., L-arginine/ADMA, L-arginine/citrulline+ornithine, and L-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS-DA) models were built to characterize systemic L-arginine metabolism and assess the effects of the supplementation. PLS-DA allowed discrimination of participants with long COVID from healthy controls with 80.2 +/- 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of L-arginine plus vitamin C supplementation, serum L-arginine concentrations and L-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID.