The following article provides an update on the latest study results on lactoferrin in use for SARS-CoV-2 infection.
At the 15th International Lactoferrin Conference in December 2021, current research on lactoferrin and COVID-19 was presented and discussed, with exciting new study results (15th International Conference on Structure, Function and Application of Lactoferrin, Beijing, China 2021).
As early as 2020, our articles (immunological functions of lactoferrin in viral defense, current data on COVID-19 and lactoferrin) described in detail that lactoferrin can be used as a defense against viruses;described in detail that lactoferrin can have a preventive and therapeutic effect through its antiviral activity in the early phase of a SARS-CoV-2 infection as well as during the infection through various mechanisms [1-3].
Recent in vitro study reports found another receptor for virus entry, the human transferrin receptor, in addition to the already described entry of SARS-CoV-2 via the ACE2 receptor and the HSPG receptor. Lactoferrin, a natural ligand of this receptor, can interact with both the spike protein and its receptor-binding domain. This allows the interaction between the receptor and the spike protein to be disrupted, effectively blocking viral entry into the cell [4].
Effect against different virus variants
Another research group investigated the effect of lactoferrin against different SARS-CoV-2 variants in vitro and was able to clearly show that lactoferrin is effective against the wild form WA1 as well as against the strains B.1.1.7 (alpha), B.1.351 (beta), P.1, Delta [5].
According to the researchers, it is expected that lactoferrin may also be effective against other emerging variants [5].
New data on the current Omikron variant is eagerly awaited.
In addition, we have already reported (Current data on COVID-19 and lactoferrin) on the first optimistic results from application studies on the efficacy of lactoferrin in the prevention and treatment of COVID-19. Consequently, these positive results could be confirmed in further studies [6-7].
Lactoferrin can significantly shorten the healing time of a SARS-CoV-2 infection as an additional therapy. Interestingly, it has also been observed that the therapeutic effect of taking lactoferrin increases with age.
This was shown in a recently published, randomized and placebo-controlled clinical study. The researchers addressed the question of whether lactoferrin in an adjusted dosage (400–1000 mg/d), depending on the severity of the symptoms, has a positive effect as an additional antiviral agent in outpatient COVID-19 patients compared to standard therapy. In fact, a shortened duration of achieving a negative real-time (RT)-PCR test for SARS-CoV-2 was observed. This was on average 15 days in pauci- to moderately symptomatic patients with lactoferrin and 24 days without lactoferrin [6].
This was confirmed by the results of a previous study, which also showed a reduction in the time to a negative SARS-CoV-2 RT-PCR test in mild to moderate and asymptomatic COVID-19 patients [7].
In addition to symptom reduction, other exciting approaches regarding the effect of lactoferrin on COVID-19 were discovered:
Lactoferrin in combination with antiviral drugs
Combination therapies are likely needed for effective treatment of SARS-CoV-2 infection, and this approach has already shown promise.
Here, the research group of Mirabelli et al. was able to show that lactoferrin enhances the antiviral activity of remdesivir and could be used in combination therapy with remdesivir, which is currently used for the treatment of COVID-19. Due to its broad availability, low cost and good safety profile, lactoferrin could be a rapidly deployable option for both prophylaxis and treatment of COVID-19.
Although the results are promising and have led to several clinical trials, further studies are needed to confirm efficacy in animal models and/or clinical trials [3].
Lactoferrin and Long COVID in children
Children have a low morbidity and mortality rate from COVID-19 infection compared to adults (Lactoferrin, the innate immune response and COVID-19) Nevertheless, Long COVID is also an important issue in children, but the current data on this is still very limited [8].
The report of a preliminary clinical trial now provides initial evidence that children with mild manifestations of Long COVID may benefit from oral administration of lactoferrin, especially those with persistent gastrointestinal symptoms. The preliminary results support the conduct of a prospective randomized and placebo-controlled trial to better define the role of lactoferrin in children with Long COVID [9].
To summarize, the study results to date indicate that the use of lactoferrin, alone or as an adjunct to standard therapy, may be a beneficial strategy for COVID-19 infection [10].
Sources
1. Carvalho, C. A. M. et al. In Vitro Inhibition of SARS-CoV-2 Infection by Bovine Lactoferrin Synthetic Anticancer Agents View project. doi:10.1101/2020.05.13.093781.
2. Lang, J. et al. Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans. PLoS ONE6, (2011).
3. Mirabelli, C. et al. Morphological cell profiling of SARS-CoV-2 infection identifies drug repurposing candidates for COVID-19. doi:10.1073/pnas.2105815118/-/DCSupplemental.
4. Lai, R. et al. Transferrin receptor is another receptor for SARS-CoV-2 entry. doi:10.21203/rs.3.rs-96962/v1.
5. Wotring, J. W., Fursmidt, R., Ward, L. & Sexton, J. Z. Evaluating the in vitro efficacy of bovine lactoferrin products against SARS-CoV-2 variants of concern. Journal of Dairy Science105, 2791–2802 (2022).
6. Rosa, L. et al. Ambulatory covid-19 patients treated with lactoferrin as a supplementary antiviral agent: A preliminary study. Journal of Clinical Medicine10, (2021).
.7 Campione, E. et al. Lactoferrin Against SARS-CoV-2: In Vitro and In Silico Evidences. Frontiers in Pharmacology12, (2021).
8. Buonsenso, D. et al. Preliminary evidence on long COVID in children. Acta Paediatrica, International Journal of Paediatrics110, 2208–2211 (2021).
9. Buonsenso, D. oral presentation 15th International Lactoferrin Conference. (2021).
10. Valenti, P. oral presentation 15th International Lactoferrin Conference. (2021).
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