Combining L-Arginine with Vitamin Improves Long-COVID Symptoms The National Multiwide LINCOLN Study Raffaele Izzo 1, Valentina Trimarco 2, Pasquale Mone 3, Teresita Aloè 4, Massimo Capra Marzani 5, Antonio Diana 6, Giovanni Fazio 7, Mario Mallardo 8, Mauro Maniscalco 9, Giuseppe Marazzi 10, Nunzia Messina 11, Simone Mininni 12, Chiara Mussi 13, Girolamo Pelaia 14, Alfio Pennisi 15, Pierachille Santus 16, Francesco Scarpelli 17, Francesco Tursi 18, Alessandro Zanforlin 19, Gaetano Santulli 20, Bruno Trimarco 1
1Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
2Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University, Naples, Italy.
3Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA.
4San Martino Hospital, Genoa, Italy.
5Alessandria Hospital, Alessandria, Italy.
6Aversa Hospital, Aversa, Caserta, Italy.
7Palermo Hospital, Palermo, Italy.
8″San Gennaro” Hospital, Naples, Italy.
9Istituti Clinici Scientifici Maugeri IRCCS, Telese Terme, Italy.
10San Raffaele Hospital, Rome, Italy.
11ASL Napoli 1, Naples, Italy.
12Associazione Scientifica Interdisciplinare Aggiornamento Medico (ASIAM), Florence, Italy.
13Department of Biomedical and Metabolic Sciences and Neuroscience, University of Modena and Reggio Emilia, Modena, Italy.
14Department of Health Science, Magna Graecia University, Catanzaro, Italy.
15Catania Hospital, Catania, Italy.
16″Luigi Sacco” University Hospital, Milan, Italy.
17Trani Hospital, Trani (BT), Italy.
18Codogno Hospital, ASST Lodi, Lodi, Italy.
19Health Authority of South Tyrol, Bolzano, Italy.
20Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy; Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA.
Abstract 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. Keywords: Ascorbic acid; COVID-19; Endothelial dysfunction; L-Arginine; Long-COVID; Oxidative stress. Keywords: Arterial stiffness; Asthma; Cardiovascular; Flow-mediated dilation; Short-acting beta agonist; Vascular function. Copyright © 2022. Published by Elsevier Ltd.