SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.

The Malnutritional Status of the Host as a Virulence Factor for New Coronavirus SARS-CoV-2

The efficacy of probiotics is currently well documented with regard to the improvement of gastrointestinal functions, whereas their potential role in the prevention of infectious respiratory diseases has not been sufficiently analyzed. PURPOSE OF THE STUDY AND METHODS: A 3-stage prospective, randomized, double blind, placebo-controlled study was carried out with several synbiotic preparations containing 3 to 5 strains of Lactobacillus plantarum, Lactobacillus rhamnosus, and Bifidobacterium lactis, lactoferrin and prebiotics such as either FOS (short-chain fructooligosaccharides) or GOS (galactooligosaccharides). The study was performed over 3 different winter seasons between 2003 and 2007, and was aimed at assessing the ability of the different preparations to improve intestinal functions and to increase the body's defences against respiratory infections. In 2003/04 (stage 1; 237 healthy volunteers) an active formulation (A) containing 3 probiotic strains and FOS was used versus placebo; in 2005/06 (stage 2; 234 healthy volunteers) the same formulation versus a similar preparation enriched with lactoferrin (B), and versus placebo; in 2006/07 (stage 3; 250 healthy volunteers), 2 new synbiotic formulations each containing 5 probiotics and FOS (C) or GOS (D), respectively, versus placebo. In stage 1, bowel functions improved (P=0.004) in terms of reduced bloating and more regular intestinal motility. The length of acute respiratory infection episodes considered as a whole (-0.97 d; P=0.007) and upper respiratory tract infections (URTIs, -1.96 d; P=0.044) were significantly decreased in the synbiotic group. The severity of episodes recorded a statistically significant drop in both episodes considered as a whole (3.21 average score vs. 3.98 in the placebo group, P<0.001) and in URTI (2.56 vs. 3.82; P=0.004) and flu classes (3.80 vs. 4.67, P=0.001). In stage 2, improvement of bowel functions was statistically significant (P=0.005) in synbiotic preparation A. A statistically significant reduction in the number of respiratory tract infections episodes was noted with both the two active formulations (P=0.002 in group A and P=0.003 in group B). The duration of episodes considered as a whole (-1.12 d in one of the 2 active formulation groups; P=0.005), URTIs (-2.08 d in group A; P=0.036) and influenza-like illness episodes (-1.40 d in group A; P=0.049) was significantly decreased in the synbiotic group. A reduction trend in cold episodes was also recorded. The severity of episodes recorded a statistically significant drop in episodes considered as a whole (-0.73 in group A, P=0.003; -0.65 in group B, P=0.004) and in the case of flu (-1.25 in group A, P<0.001; -1.18 in group B, P<0.001). In stage 3, the improvement of bowel functions was confirmed for both active formulations (P<0.001). A significant decrease in the total length of respiratory episodes (-1.51 d; P<0.001 in the group C and -1.39 d; P<0.001 in the group D) and in the length of cough (-3.08 d; P<0.001 in group C; -2.83 d; P<0.001 in group D), cold (-1.02 d; P=0.019 in group C; -1.32 d; P=0.001 in group D) and flu episodes was reported. The severity of episodes recorded a statistically significant drop in regard to episodes considered as a whole, the cold and flu classes in both groups and for cough too in group C. The number of episodes also dropped considerably in terms of overall episodes, cold (group C) and flu. These results demonstrate that a regular, long-term intake of various synbiotics may improve health by reducing the incidence and severity of respiratory diseases during the cold season.