Abstract: Journal of Clinical Medicine Article Ambulatory COVID-19 Patients Treated with Lactoferrin as a Supplementary Antiviral Agent: A Preliminary Study Luigi Rosa 1, * , Giovanni Tripepi 2 , Enrico Naldi 3 , Marina Aimati 4 , Stefano Santangeli 5 , Francesco Venditto 6 , Marcello Caldarelli 7 and Piera Valenti 1 1 2 3 4 5 6 7 * Department of Public Health and Infectious Diseases, University of Rome “La Sapienza”, 00185 Rome, Italy; piera.valenti@uniroma1.it National Research Council (CNR), Institute of Clinical Physiology (IFC), Clinical Epidemiology of Renal Diseases and Hypertension, Ospedali Riuniti, 89124 Reggio Calabria, Italy; gtripepi@ifc.cnr.it General Practitioner, 50136 Florence, Italy; enrico.naldi60@virgilio.it General Practitioner, 04011 Aprilia, Italy; marina.aimati@gmail.com General Practitioner, Barberino del Mugello, 50031 Florence, Italy; dott.santangeli@alice.it General Practitioner, 50124 Florence, Italy; fravend@katamail.com General Practitioner, 00178 Rome, Italy; studio.drcaldm@gmail.com Correspondence: luigi.rosa@uniroma1.it; Tel.: +39-06-4991-4543 A. Martín-Acebes Abstract: SARS-CoV-2, an enveloped, single-stranded RNA virus causing COVID-19, exerts morbidity and mortality especially in elderly, obese individuals and those suffering from chronic conditions. In addition to the availability of vaccines and the limited efficacy of the first dose of vaccine against SARS-CoV-2 variants, there is an urgent requirement for the discovery and development of supplementary antiviral agents. Lactoferrin (Lf), a pleiotropic cationic glycoprotein of innate immunity, has been proposed as a safe treatment combined with other therapies in COVID-19 patients. Here, we present a small retrospective study on asymptomatic, paucisymptomatic, and moderate symptomatic COVID-19 Lf-treated versus Lf-untreated patients. The time required to achieve SARS-CoV-2 RNA negativization in Lf-treated patients (n = 82) was significantly lower (p < 0.001) compared to that observed in Lf-untreated ones (n = 39) (15 versus 24 days). A link among reduction in symptoms, age, and Lf treatment was found. The Lf antiviral activity could be explained through the interaction with SARS-CoV-2 spike, the binding with heparan sulfate proteoglycans of cells, and the anti-inflammatory activity associated with the restoration of iron homeostasis disorders, which favor viral infection/replication. Lf could be an important supplementary treatment in counteracting SARS-CoV-2 infection, as it is also safe and well-tolerated by all treated patients. Received: 27 July 2021 Keywords: lactoferrin; COVID-19 patients; SARS-CoV-2



 Citation: Rosa, L.; Tripepi, G.; Naldi, E.; Aimati, M.; Santangeli, S.; Venditto, F.; Caldarelli, M.; Valenti, P. Ambulatory COVID-19 Patients Treated with Lactoferrin as a Supplementary Antiviral Agent: A Preliminary Study. J. Clin. Med. 2021, 10, 4276. https://doi.org/10.3390/ jcm10184276 Academic Editor: Miguel Accepted: 17 September 2021 Published: 21 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).