There is currently no clinically proven specific antiviral agent available for SARS-CoV-2 infection. Supportive treatment, including oxygen therapy, remains the most important management strategy. Since its discovery, lactoferrin and its related peptides are mainly considered to be important non-specific host defense molecules against a broad range of viruses including SARS-CoV, which is closely related to SARS-CoV-2 that causes COVID-19. Lactoferrin has been found to experimentally inhibit viral entry in murine coronavirus, and human coronaviruses hCOV-NL63 and pseudotyped SARS-CoV. Besides reducing viral entry, lactoferrin can also suppress virus replication after the viral entry. Another major aspect of lactoferrin bioactivity relates to its immunomodulatory and anti-inflammatory functions. Current thinking suggests that mortality from COVID-19 is not simply due to viral infection but is a result of a cytokine storm associated with hyper-inflammation leading to acute respiratory distress and subsequent mortality. A cytokine profile in severe COVID-19 cases is characterized by increases in cytokines and acute phase reactants and ferritin. In this regard, lactoferrin was demonstrated to reduce IL-6, TNF a, and downregulate ferritin in experimental settings simulating sepsis. In this study, we aim to study the potential application of lactoferrin against SARS-CoV-2 and propose the possibility of using different doses of supplemental lactoferrin as a potential adjunct treatment for COVID-19.
COVID-19 has a wide clinical spectrum ranging between asymptomatic infection, mild upper
respiratory tract symptoms, and severe viral pneumonia that may result in respiratory failure
and finally death. There is currently no clinically proven specific antiviral agent available
for SARS-CoV-2 infection. Supportive treatment, including oxygen therapy, conservation fluid
management, and broad-spectrum antibiotics to cover secondary bacterial infection, remains
the most important management strategy.
Lactoferrin is a highly conserved pleiotropic iron-binding 80-kDa glycoprotein of the
transferrin family that is expressed and secreted by glandular cells and found in most body
fluids with especially high concentrations in mammalian milk. Since its discovery,
lactoferrin and its related peptides are mainly considered to be important non-specific host
defense molecules against a broad range of viruses including SARS-CoV, which is closely
related to SARS-CoV-2 that causes COVID-19. Lactoferrin has been found to experimentally
inhibit viral entry in murine coronavirus, and human coronaviruses hCOV-NL63 and pseudotyped
SARS-CoV. Given the homology of SARS-CoV and SARS-CoV-2 spike protein structures, as well as
both viruses depending on the same ACE2 receptor for cell entry, it is likely that
lactoferrin can inhibit SARS-CoV-2 invasion as in the case of SARS-CoV. Besides reducing
viral entry, lactoferrin can also suppress virus replication after the viral entry as in the
case of HIV.
Another major aspect of lactoferrin bioactivity relates to its immunomodulatory and
anti-inflammatory functions. Current thinking suggests that mortality from COVID-19 is not
simply due to viral infection but is a result of a cytokine storm associated with
hyper-inflammation leading to acute respiratory distress and subsequent mortality. A cytokine
profile in severe COVID-19 cases is characterized by increases in cytokines and acute phase
reactants such as interleukin IL-6, tumor necrosis factor-a (TNFa) and ferritin. In this
regard, lactoferrin was demonstrated to reduce IL-6, TNF a, and downregulate ferritin in
experimental settings simulating sepsis.
The aim of this study is to confirm the antiviral properties and immunomodulatory mechanisms
of lactoferrin within the context of its potential application against SARS-CoV-2 and propose
the possibility of supplemental lactoferrin in different doses as a potential adjunct
treatment for COVID-19.
The clinical data as well as the demographic information will be collected from the
clinicians involved in the project. All samples will be collected according to the approved
research protocols. During this period, the database entry platforms will be formed.
Eligible patients will be randomly distributed in 3 groups:
Group 1 (n=50): standard of care treatment; as per Egyptian Ministry of Health and Population
(MOHP) protocol, in addition to 400 mg oral lactoferrin daily Group 2 (n=50): standard of
care treatment; as per MOHP protocol, in addition to 600 mg oral lactoferrin daily Group 3
(n=50): standard of care treatment; as per MOHP protocol (control group)
The trial will be done according to the principles of the Declaration of Helsinki and the
Good Clinical Practice guidelines.
Patients will be assessed daily on a scale reflecting a range from uninfected to dead, where
0 is "no clinical or virological evidence of infection", 1 is "no limitation of activities",
2 is "limitation of activities", 3 is "hospitalized, no oxygen therapy", 4 is "oxygen by mask
or nasal prongs", 5 is "non-invasive ventilation or high-flow oxygen", 6 is "intubation and
mechanical ventilation", 7 is "ventilation + additional organ support - pressors, RRT (renal
replacement therapy), ECMO (extracorporeal membrane oxygenation)", and 8 is "death".
Serial oropharyngeal swab samples will be obtained after treatment until discharge or death
had occurred.
Drug: Lactoferrin
adding lactoferrin to standard of care treatment regimens
Other Name: Standard of care treatment regimens
Inclusion Criteria:
- Positive reverse-transcriptase-polymerase chain- reaction (RT-PCR) assay for SARS-
CoV-2 in a respiratory tract sample.
Exclusion Criteria:
- Known allergy or hypersensitivity to the used medications
- Severe symptoms: respiratory insufficiency that requires admission in intensive care
unit or mechanical ventilation