Lactoferrin, the innate immune response and COVID-19

Who is getting sick with a COVID-19 infection? The following article deals with the question of what factors are being considered when it comes to explaining the low rates of illness and death in children. 
Children rarely become seriously ill with COVID-19 and almost never die of it. [1,2] The incidence numbers of illness and death in children are significantly lower than average, even lower in infants and young children, a phenomenon that is found in all countries worldwide. [3,4]
An interesting hypothesis put forward to address this, says the following: Children may be protected by antiviral proteins from milk, such as Lactoferrin and casein, and by maternal antibodies. Breast milk offers a broad protection against infections and protects the child until their own immune system is mature.  Certain antiviral proteins are also added in baby food, which provide a certain protection. [3,5]  
Although the human and bovine lactoferrin (derived from cows’ milk) are almost identical, the small amounts of lactoferrin in milk as a food appear to be insufficient for a health-promoting effect.  A study reviewing individual countries, showed no correlation between milk consumption and the occurrence of COVID-19 infections [3].
In view of the effective protection against illness provided by lactoferrin and other milk proteins in children, the authors of the above articles recommend investigating the possibilities of Lactoferrin use as a supplement in adults.
One reason why nasal and oral sprays with Lactoferrin are used for testing in clinical trials [6] is that lactoferrin is active in the innate defences within the body barriers, such as the mucous membranes in the lungs and digestive tract, these being the main route of access of the virus into the body. [7]  
This hypothesis is now being tested, as already described in our previous article.
Other publications also discuss the low disease and death rate in children.  Also mentioned is the increased activity of the innate immune defence, which includes Lactoferrin, as an effective defence against SARS-CoV2 in children.
The human immune system consists of two components: innate immunity and acquired immunity. The first reacts quickly and non-specifically, the second response is somewhat delayed, but more targeted and more energy efficient. In children, the first component of immune defence predominates and this is showing successful in the fight against COVID-19.
This first rapid and widespread reaction of the immune system effectively prevents the viruses from spreading in the first place, and thus prevents systemic infection, which can cause severe progression in adults [7].
As early as 2005, an increased activity of the innate immune system was observed in patients with infection by SARS [8]. In 2005, a study conducted by Reghunatan, et al. showed that in this case, the innate immune system reacted much more intensively than the specific immune response. Several genes were highly upregulated in patients with SARS, such as the genes that code for Lactoferrin, S100A9 and lipocalin 2. 
This differential profile of gene expression in patients with SARS strongly indicated that the response appears to be primarily by the innate immune system.
It seems that SARS produces a different immune response when compared to the influenza virus, for example; it uses a different strategy to bypass immune defences. 
Cristiani, et al. provide further partial explanations for the lower severity of illness observed in children [2]. High ACE2-receptor concentration in children could be a protective factor, as could also a trained immunity, due to frequent contact with related viruses.
Children generally have a higher number of lymphocytes than adults, especially natural killer cells. The number is particularly high in the first months of life and is significantly lower in the older child and adolescent. [9]
Further findings are provided by van Eeden et al. in 2020 [10]. They emphasise in their work the importance of a precise and regulated immune response for effective virus control.  The problem is this often doesn’t exist.  Factors such as age, cancers, autoimmunity or cardiovascular diseases distort the immune response, further exacerbated by the viral infection. People dying from COVID-19 often die from the effects of what’s known as the “cytokine storm“ – this happens more often in elderly patients and patients with cardiovascular diseases. Here, natural killer cells play a decisive role in immunomodulation and these are significantly less effective in the above-mentioned groups.  Studies in COVID-19 patients with severe progression showed that the number and function of natural killer cells was significantly reduced.
And here we close the loop, encompassing the importance of the body’s own well-functioning immune defence. Substances which can help regulate and optimise this, have the potential to contribute to the prophylaxis and therapy of SARS-Cov2.
The broad capabilities of lactoferrin remain promising in this sector. It acts as part of the natural barriers in both respiratory and intestinal mucosa.  It has a regulating effect on problems with iron imbalances, which can be associated with viral infections. It modulates the immune response and regulates proinflammatory cytokines released by viral inflammation. 
In these respects, lactoferrin is a promising active ingredient for the prevention and treatment of SARS CoV2, and is virtually free from the risk of possible adverse reactions. [7]