Potential Role of Lactoferrin in COVID-19 in Children

Background: The Coronavirus disease 2019 (COVID-19) outbreak present a significant lower prevalence of paediatric COVID-19 cases. Studies suggest an implication of the innate inflammatory response related to various particularly up-regulated genes, such as the ones coding for Lactoferrin (LF). LF has a significant activity in the innate immune system and can enhance child’s immunity against bacterial and viral infections.

Objective: We aim to analyze the characteristics of LF that could influence COVID-19, and encourage clinical trials to investigate this association especially in children.

Methods: Pubmed, Embase, and Cochrane database were screened for potentially eligible articles.

Results: Findings underline the ability of LF to inhibit the entry and replication into the host cell involving multi-mechanisms, such as direct biding to the pathogen particles, blocking their cellular receptors, or stabilizing immune factors to improve host’s antiinflammatory response. Studies in vitro have established that LF prevent the entry of both DNA and RNA viruses, including Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), which commonly utilize heparan sulfate proteoglycans (HSPGs) on host cell membrane for internalization. LF can take an important part against COVID-19, not only with its antiinflammation role in restricting tissue damage by directly restoring iron homeostasis and immunomodulating pro-inflammation molecules, but also by blocking SARS-CoV-2 internalization by competitively biding to HSPGs. LF explicate an immunomodulation activity controlling the release of proinflammatory cytokines, like IL-6 and TNFα, while increase phagocytosis. Also, this glycoprotein directly bind iron, preventing oxidative stress induced by reactive oxygen species that forms during excess inflammatory response. Consequentially, this suggests that LF could explicate a preventive role in hypercoagulation and low thrombocyte levels in COVID-19.

Conclusion: LF may present a new safe approach for the prevention and treatment of COVID-19.