1. Introduction
respiratory syndrome coronavirus, death
CORONAVIRUS, SARS-COV-2 INFECTION, MIDDLE EAST RESPIRATORY SYNDROME, DISEASE COURSE
These authors contributed equally to this work.As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63–1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70–1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19.Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a positive, single-stranded β-coronavirus, showing high genetic similarities to both SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) [Although the vaccination campaign and the implementation of targeted treatments early in the disease course have lowered the risk of developing severe COVID-19, the current in-hospital mortality of unvaccinated subjects remains quite high [In this scenario, several drugs and natural products have been proposed as candidate treatments for COVID-19, owing to their presumed antiviral efficacy or immunomodulatory effects [Several studies have shown how bovine lactoferrin can interfere with SARS-CoV and SARS-CoV-2 infections in vitro by either enhancing natural killer (NK) cell and neutrophil activities, boosting interferon-mediated immune responses, or blocking viral internalization via binding to HSPGs [Bovine lactoferrin is commercially available as a generally recognized as safe (GRAS) nutritional supplement, with a high homology to the human protein and very similar biological activities [In light of the above properties, lactoferrin has been tested in a few non-randomized pilot studies in patients with COVID-19 with controversial results [