Lactoferrin as Immune-Enhancement Strategy for SARS-CoV-2 Infection in Alzheimer's Disease Patients

Abstract

Coronavirus 2 (SARS-CoV2) (COVID-19) causes severe acute respiratory syndrome. Severe illness of COVID-19 largely occurs in older people and recent evidence indicates that demented patients have higher risk for COVID-19. Additionally, COVID-19 further enhances the vulnerability of older adults with cognitive damage. A balance between the immune and inflammatory response is necessary to control the infection. Thus, antimicrobial and anti-inflammatory drugs are hopeful therapeutic agents for the treatment of COVID-19. Accumulating evidence suggests that lactoferrin (Lf) is active against SARS-CoV-2, likely due to its potent antiviral and anti-inflammatory actions that ultimately improves immune system responses. Remarkably, salivary Lf levels are significantly reduced in different Alzheimer's disease (AD) stages, which may reflect AD-related immunological disturbances, leading to reduced defense mechanisms against viral pathogens and an increase of the COVID-19 susceptibility. Overall, there is an urgent necessity to protect AD patients against COVID-19, decreasing the risk of viral infections. In this context, we propose bovine Lf (bLf) as a promising preventive therapeutic tool to minimize COVID-19 risk in patients with dementia or AD.

Keywords: Alzheimer’s disease; COVID-19; SARS-CoV2; brain-immunity interactions; dementia; inflammation; lactoferrin; saliva.

Figure 1

Schematic representation of potential mechanisms of SARS-CoV-2 infection in neurodegeneration. SARS-CoV-2 infection causes severe upregulation of proinflammatory cytokines and chemokines (so called “cytokine storm”) leading to increased permeability of BBB and blood-CSF barrier, and initiating CNS invasion This event also involves overactivation of glial cells that can promote detrimental effects, indirectly and/or directly, by inducing synapse loss, oxidative injury and further contributing to neuronal degeneration.

Figure 2

Potential role of Lf in the relationship between AD brain pathology and COVID-19. Pathogenic events leading to neuronal damage may impair the host defense system which in turn reduce AMP production, including Lf, and influence the extent of SARS-CoV-2 infection in the brain. Additionally, potential antiviral mechanisms of Lf are shown: (1) by modulating SARS-CoV-2 induced inflamation, reducing pro-inflammatory cytokine levels, such as IL-6 and TNFα; (2) by occupying binding sites of SARS-CoV-2, as heparan sulfate proteoglycans (HSPGs) on the host cell surface, reducing viral surfing and subsequent viral entry; and (3) by inhibition of viral replication via induction of intracellular cell signals. AD, Alzheimer’s disease; Lf, lactoferrin; AMP, antimicrobial peptide; BBB, blood-brain barrier.