Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

Abstract

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.

Keywords: COVID-19; double-blind clinical trial; lactoferrin; multicenter; placebo-controlled; randomized.

Figure 1

Flow diagram. The flow diagram shows the number of subjects assessed for eligibility, randomized, randomized and receiving intervention, randomized and withdrawing consent before treatment initiation, and included in the primary analysis. Patients who were eligible but not randomized, who were not randomly allocated, who were lost to follow-up, and who discontinued the intervention are also reported.

Figure 2

Changes in inflammatory markers between lactoferrin and placebo arms. CRP (a), IL-6 (b), and ferritin (c) plasma levels measured at different time points (t0, t7, t14). Circles represent the placebo arm, while triangles represent the lactoferrin one. Data are reported as median values (dashed lines) and interquartile range (bold lines).