Bovine lactoferrin for the prevention of COVID-19 infection in health care personnel: a double-blinded randomized clinical trial (LF-COVID)
Rafaella Navarro, Jose Luis Paredes, Lourdes Tucto, Carlos Medina, Eddie Angles-Yanqui, Juan Carlos Nario, Jorge Ruiz-Cabrejos, Juan Luis Quintana, Kevin Turpo-Espinoza, Fernando Mejia-Cordero, Meylin Aphang-Lam, Jorge Florez, Gabriel Carrasco-Escobar, Theresa Jean Ochoa
BioMetals, doi:10.1007/s10534-022-00477-3
suspected episodes. A serological test was obtained from all participants at the end of the intervention. The main outcome included symptomatic and asymptomatic cases. A sub-analysis explored the time to symptomatic infection. Secondary outcomes were the severity, frequency, and duration of symptomatic infection. The study was prematurely cancelled due to the availability of vaccines against SARS-CoV-2 in Peru. 209 participants were enrolled and randomized, 104 received bLF and 105 placebo. SARS-CoV-2 infection occurred in 11 (10.6%) participants assigned to bLF and in 9 (8.6%) participants assigned to placebo without significant differences (Incidence Rate Ratio = 1.23, 95%CI 0.51-3.06, p-value = 0.64). There was no significant effect of bLF on time to symptomatic infection (Hazard Ratio = 1.61, 95%CI 0.62-4.19, p-value = 0.3). There were no significant Abstract Lactoferrin (LF) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to determine the effect of bovine lactoferrin (bLF) in the prevention of SARS-CoV-2 infection in health care personnel. A randomized, double-blinded, placebo-controlled clinical trial was conducted in two tertiary hospitals that provide care to patients with SARS-CoV-2 infection in Lima, Peru. Daily supplementation with 600 mg of enteral bLF versus placebo for 90 days was compared. Participants were weekly screened for symptoms suggestive of SARS-CoV-2 infection and molecular testing was performed on
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s10534-022-00477-3. Duration and prevalence of secondary outcomes are shown in Table 3 . The most common symptoms among the 18 symptomatic SARS-CoV-2 infections were: cough in 11 participants (61%), nasal secretion in 10 (56%), headache in 8 (44%), and sore throat in 8 (44%). The proportion of patients who developed fever during the study period and the duration of fever were slightly lower t in bLF than in the placebo group, but not significant different (Table 3 ).
References
Beljaars, Van Der Strate, Bakker, Reker-Smit, Van Loenen-Weemaes et al., Inhibition of cytomegalovirus infection by lactoferrin in vitro and in vivo, Antivir Res,
doi:10.1111/j.1574-6968.1996.tb08579.xBerlutti, Schippa, Morea, Sarli, Perfetto et al., Lactoferrin downregulates proinflammatory cytokines upexpressed in intestinal epithelial cells infected with invasive or noninvasive Escherichia coli strains, Biochem Cell Biol
Berthon, Williams, Williams, Wood, Effect of lactoferrin supplementation on inflammation, immune function, and prevention of respiratory tract infections in humans: a systematic review and meta-analysis, Adv Nutr,
doi:10.1093/advances/nmac047Biase, Pietrantoni, Tinari, Siciliano, Valenti et al., Heparin-interacting sites of bovine lactoferrin are involved in anti-adenovirus activity, J Med Virol
Chang, Ng, Sun, Lactoferrin as potential preventative and adjunct treatment for COVID-19, Int J Antimicrob Agents
Chen, Chai, Li, Zhang, Xie et al., Effect of bovine lactoferrin from iron-fortified formulas on diarrhea and respiratory tract infections of weaned infants in a randomized controlled trial, Nutrition
Drobni, Näslund, Evander, Lactoferrin inhibits human papillomavirus binding and uptake in vitro, Antivir Res
Figueroa, Bottazzi, Hotez, Batista, Ergonul et al., Urgent needs of low-income and middle-income countries for COVID-19 vaccines and therapeutics, Lancet
Hanson, Caliendo, Arias, Englund, Lee et al., ica guidelines on the diagnosis of COVID-19, Infectious Diseases Society of Amer
Harris, Taylor, Minor, Elliott, Fernandez et al., The REDCap consortium: building an international community of software platform partners, J Biomed Inform
Harris, Taylor, Thielke, Payne, Gonzalez et al., Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support, J Biomed Inform
Ishikawa, Awano, Fukui, Sasaki, Kyuwa, The protective effects of lactoferrin against murine norovirus infection through inhibition of both viral attachment and replication, Biochem Biophys Res Commun
Lang, Yang, Deng, Liu, Yang et al., Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans, PLoS ONE
Legrand, Overview of lactoferrin as a natural immune modulator, J Pediatr
Lizzi, Carnicelli, Clarkson, Bovine lactoferrin and its tryptic peptides: antibacterial activity against different species, Appl Biochem Microbiol,
doi:10.1134/S0003683816040116Marchetti, Trybala, Superti, Johansson, Bergström, Inhibition of herpes simplex virus infection by lactoferrin is dependent on interference with the virus binding to glycosaminoglycans, Virology
Oda, Wakabayashi, Tanaka, Yamauchi, Sugita et al., Effects of lactoferrin on infectious diseases in Japanese summer: a randomized, double-blinded, placebo-controlled trial, J Microbiol Immunol Infect,
doi:10.1016/j.jmii.2020.02.010Reghunathan, Jayapal, Hsu, Chng, Tai et al., Expression profile of immune response genes in patients with severe acute respiratory syndrome, BMC Immunol
Serrano, Kochergina, Albors, Diaz, Oroval et al., Liposomal lactoferrin as potential preventative and cure for COVID-19, Int J Res Health Sci
Shah, Wood, Gribben, Caldwell, Bishop et al., Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study,
doi:10.1136/bmj.m3582Superti, Siciliano, Rega, Giansanti, Valenti et al., Involvement of bovine lactoferrin metal saturation, sialic acid and protein fragments in the inhibition of rotavirus infection, Biochim Biophys Acta
Vitetta, Coulson, Beck, Gramotnev, Du et al., The clinical efficacy of a bovine lactoferrin/whey protein Ig-rich fraction (Lf/IgF) for the common cold: a double blind randomized study, Complement Ther Med
