Lactoferrin is a nutrient classically found in mammalian milk. It binds iron and is transferred via a variety of receptors into and between cells, serum, bile, and cerebrospinal fluid. It has important immunological properties, and is both antibacterial and antiviral. In particular, there is evidence that it can bind to at least some of the receptors used by coronaviruses and thereby block their entry. Of importance are Heparan Sulfate Proteoglycans (HSPGs) and the host receptor angiotensin-converting enzyme 2 (ACE2), as based on other activities lactoferrin might prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from attaching to the host cells. Lactoferrin (and more specifically enteric-coated LF because of increased bioavailability) may consequently be of preventive and therapeutic value during the present COVID-19 pandemic.

Lactoferrin (LF) or lactotransferrin has recently come under the spotlight, particularly with regards to the new coronavirus pandemic that started in 2019 (COVID-19). Diet and supplements support a well-functioning immune system, and favorably influence the body’s ability to fight infection. Although LF is produced by the body itself, as a secretion by exocrine glands (such as maternal milk or tears) and secondary granules of human neutrophils (1), it can also be taken as a supplement, where it then acts as nutraceutical or functional food. Our particular focus is on its role as an oral supplement. Here we also collate some of the evidence that shows how LF may be an important nutrient to support host immunity, including as an antibacterial and antiviral agent, but particularly with the current COVID-19 pandemic in mind.

We summarize what is already known about LF, including its immunological properties, as well as its antibacterial and antiviral activities. We also discuss how LF uses Heparan Sulfate Proteoglycans (HSPGs) on cell surfaces to facilitate entry. This is of particular importance to coronaviruses, as these viruses are considered to bind to the host cell by attaching first to HSPGs using them as preliminary docking sites on the host cell surface. LF is known to interfere with some of the receptors used by coronaviruses, it may thus contribute to the prevention and treatment of SARS CoV-2 infections. In COVID-19 infection, LF may therefore have a role to play, not only sequestering iron and inflammatory molecules that are severely increased during the cytokine burst, but also possibly in assisting by occupying receptors and HSPGs.

But new findings from a team of researchers led by scientists at Washington University School of Medicine in St. Louis point to another theory and suggest that patients become ill because their immune systems can’t do enough to protect them from the virus, landing them in intensive care units. They suggest that boosting immunity could be a potential treatment strategy for COVID-19.

Such a strategy has been proposed in two recently published papers, one published online in JAMA Network Open and the other published online in the journal JCI Insight.

“People around the world have been treating patients seriously ill with COVID-19 using drugs that do very different things,” said senior investigator Richard S. Hotchkiss, MD, professor of anesthesiology, of medicine and of surgery. “Some drugs tamp down the immune response, while others enhance it. Everybody seems to be throwing the kitchen sink at the illness. It may be true that some people die from a hyperinflammatory response, but it appears more likely to us that if you block the immune system too much, you’re not going to be able to control the virus.”