Combining L-Arginine with Vitamin C Improves Long-COVID Symptoms: The Nationwide Multicenter LINCOLN Study.

INTRODUCTION: Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms. METHODS: We designed a nationwide multicenter clinical study (LINCOLN: L-Arginine and Vitamin C improves Long-COVID), in which a survey assessing several symptoms that have been associated with Long-COVID was administered to COVID-19 survivors; effort perception was measured using the Borg scale. Patients were divided in two groups, with a 2:1 ratio: the first group included patients treated with L-Arginine + Vitamin C, whereas the second group was treated with a multivitamin combination (alternative treatment). Before administering the survey, patients completed 30 days of treatment. RESULTS: 1590 patients were initially enrolled, of which 1390 completed the study. Following a 30-day treatment with L-Arginine + Vitamin C, the survey revealed that patients in this treatment group had significantly lower scores compared to the other group. There were no other significant differences between the two groups. When examining effort perception, we observed a significantly lower value (p<0.0001) in patients receiving L-Arginine + Vitamin C compared to the alternative-treatment arm. CONCLUSIONS: Taken together, our findings indicate that the supplementation with L-Arginine + Vitamin C has beneficial effects in Long-COVID, in terms of reducing its typical symptoms and improving effort perception.