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

Rosa, Luigi; Valenti, Piera; Lopera, Francisco; Hernández-Gallego, Jesús; Cantero, José L.; Orive, Gorka; Carro, Eva

doi:10.3389/fimmu.2022.878201

Cited by 6 publications

(5 citation statements)

References 143 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…That is why Lf seems a prospective competitor of SARS-CoV-2 in its interaction with TfR. Such property of Lf should not be neglected, but the fact that Lf interacts with TfR has been omitted from a number of the most recent reviews concerning its functions (Mahidhara et al 2015 ; Kell et al 2020 ; Bartolomé et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is worth noting that Tf and Lf also interact with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) which mediates Tf uptake and a rapid response to hypoxia (Kumar et al 2012 ; Rawat et al 2012 ; Malhotra et al 2019 ). Other recent reviews on Lf structure and functions include its interactions with intelectin-1 (omentin-1), CD14, chemokine receptor 4 (CXCR4), and low-density lipoprotein receptor-related protein (LRP) in cellular receptors list, but interaction of Lf with TfR1 received little attention (Li and Guo 2021 ; Artym et al 2021 ; Suzuki et al 2005 ; Lepanto et al 2019 ; Elzoghby et al 2020 ; Godínez-Chaparro et al 2021 ) or was fully neglected (Kawakawi et al 1990 ; Mahidhara et al 2015 ; Kell et al 2020 ; Bartolomé et al 2022 ). Interestingly, TfR1 is regarded as cellular receptor of Lf in a recent survey of its antiviral activity, and the corresponding scheme is presented (Ward et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin

et al. 2022

View full text Add to dashboard Cite

The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection involves dysregulations of iron metabolism, and although the mechanism of this pathology is not yet fully understood, correction of iron metabolism pathways seems a promising pharmacological target. The previously observed effect of inhibiting SARS-CoV-2 infection by ferristatin II, an inducer of transferrin receptor 1 (TfR1) degradation, prompted the study of competition between Spike protein and TfR1 ligands, especially lactoferrin (Lf) and transferrin (Tf). We hypothesized molecular mimicry of Spike protein as cross-reactivity of Spike-specific antibodies with Tf and Lf. Thus, strong positive correlations (R 2 > 0.95) were found between the level of Spike-specific IgG antibodies present in serum samples of COVID-19-recovered and Sputnik V-vaccinated individuals and their Tf-binding activity assayed with peroxidase-labeled anti-Tf. In addition, we observed cross-reactivity of Lf-specific murine monoclonal antibody (mAb) towards the SARS-CoV-2 Spike protein. On the other hand, the interaction of mAbs produced to the receptor-binding domain (RBD) of the Spike protein with recombinant RBD protein was disrupted by Tf, Lf, soluble TfR1, anti-TfR1 aptamer, as well as by peptides RGD and GHAIYPRH. Furthermore, direct interaction of RBD protein with Lf, but not Tf, was observed, with affinity of binding estimated by K D to be 23 nM and 16 nM for apo-Lf and holo-Lf, respectively. Treatment of Vero E6 cells with apo-Lf and holo-Lf (1–4 mg/mL) significantly inhibited SARS-CoV-2 replication of both Wuhan and Delta lineages. Protective effects of Lf on different arms of SARS-CoV-2-induced pathogenesis and possible consequences of cross-reactivity of Spike-specific antibodies are discussed. Supplementary Information The online version contains supplementary material available at 10.1007/s10534-022-00458-6.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The first hypothesis may be approached by the investigation of the possible role in SARS-CoV-2 infection rates of oropharyngeal dysphagia, common in dementia, 181 and the effect of reduced salivary lactoferrin levels in Alzheimer's disease, which will reduce the defence mechanisms against SARS-CoV-2 and increase COVID-19 susceptibility. 189 The second one would require an investigation of the clinical significance of some changes in peripheral blood cell profiles involved at least in Alzheimer's disease and related to inflammation and immune dysfunction, such as the CD4/CD8 ratio, 190 which in turn may contribute to severe COVID-19. 191 In addition, individuals homozygous for apolipoprotein E (APOE) ε4 have shown a higher risk of COVID-19-related hospital admission, which could be explained by the changes associated with APOE ε4 that lead to extensive central nervous system inflammation, neurodegeneration and aggressive inflammatory response due to increased blood-brain barrier permeability, exacerbated microglia-mediated neuroinflammation and increased cytokine production in response to inflammatory stimuli.…”

Section: Susceptibility For Sars-cov-2 Infection and Neurodegenerativ...mentioning

confidence: 99%

SARS-CoV-2 susceptibility and COVID-19 illness course and outcome in people with pre-existing neurodegenerative disorders: systematic review with frequentist and Bayesian meta-analyses

Smadi,

Kaburis,

Schnapper

et al. 2023

Br J Psychiatry

View full text Add to dashboard Cite

Background People with neurodegenerative disease and mild cognitive impairment (MCI) may have an elevated risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may be disproportionally affected by coronavirus disease 2019 (COVID-19) once infected. Aims To review all eligible studies and quantify the strength of associations between various pre-existing neurodegenerative disorders and both SARS-CoV-2 susceptibility and COVID-19 illness course and outcome. Method Pre-registered systematic review with frequentist and Bayesian meta-analyses. Systematic searches were executed in PubMed, Web of Science and preprint servers. The final search date was 9 January 2023. Odds ratios (ORs) were used as measures of effect. Results In total, 136 primary studies (total sample size n = 97 643 494), reporting on 268 effect-size estimates, met the inclusion criteria. The odds for a positive SARS-CoV-2 test result were increased for people with pre-existing dementia (OR = 1.83, 95% CI 1.16–2.87), Alzheimer's disease (OR = 2.86, 95% CI 1.44–5.66) and Parkinson's disease (OR = 1.65, 95% CI 1.34–2.04). People with pre-existing dementia were more likely to experience a relatively severe COVID-19 course, once infected (OR = 1.43, 95% CI 1.00–2.03). People with pre-existing dementia or Alzheimer's disease were at increased risk for COVID-19-related hospital admission (pooled OR range: 1.60–3.72). Intensive care unit admission rates were relatively low for people with dementia (OR = 0.54, 95% CI 0.40–0.74). All neurodegenerative disorders, including MCI, were at higher risk for COVID-19-related mortality (pooled OR range: 1.56–2.27). Conclusions Our findings confirm that, in general, people with neurodegenerative disease and MCI are at a disproportionally high risk of contracting COVID-19 and have a poor outcome once infected.

show abstract

“…The high viral spread of the SARS-CoV-2 raised successive sequela of long-term concerns particular to those with underlying severe neuro-medical illnesses, leaving patients with severe additional impairments to their functional disabilities [ 2 ]. These CNS complications are caused via the SARS-CoV-2’s inflammatory responses within the immune system, with additional consequences resulting in patients with symptoms of ischemic or hemorrhagic stroke having a higher risk of mortality than other hospitalized patients [ 3 ]. Patients exhibiting pre-existing brain pathologies- such as dementia and Alzheimer's- experienced exacerbating symptoms that caused the further cognitive functional decline.…”

Section: Introductionmentioning

confidence: 99%

Exacerbation of Pre-existing Neurological Symptoms With COVID-19 in Patients With Chronic Neurological Diseases: An Updated Systematic Review

Sakibuzzaman¹,

Hassan²,

Hayee³

et al. 2022

Cureus

View full text Add to dashboard Cite

The neurotropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can potentially explain the worsening of symptoms in patients with a history of neurological conditions such as stroke, Parkinson's disease, Alzheimer's, and epilepsy. Several studies have reported that these pre-existing conditions may worsen with a higher frequency of flare-ups, thus resulting in a more significant risk of patient mortality. In this review, we sought to provide an overview of the relationship between pre-existing neurological disorders and COVID-19, focusing on whether the initial infection directly influenced the severity of symptoms. We systematically searched the electronic database PubMed (MEDLINE) and used specific keywords related to our aims from January 2020 to July 2022. All articles published on COVID-19 with keywords pertaining to pre-existing neurological diseases were retrieved and subsequently analyzed. After independent review, the data from 107 articles were selected and evaluated. After analyzing the data from selected articles reviewing the effect of COVID-19 on neurological conditions, we have documented the relationship between said pre-existing neurological diseases, showing an increased risk of hospitalization, admission length, worsening of symptoms, and even mortality in COVID-19 patients.

show abstract

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

Cited by 6 publications

References 143 publications

Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin

Molecular mimicry of the receptor-binding domain of the SARS-CoV-2 spike protein: from the interaction of spike-specific antibodies with transferrin and lactoferrin to the antiviral effects of human recombinant lactoferrin

SARS-CoV-2 susceptibility and COVID-19 illness course and outcome in people with pre-existing neurodegenerative disorders: systematic review with frequentist and Bayesian meta-analyses

Exacerbation of Pre-existing Neurological Symptoms With COVID-19 in Patients With Chronic Neurological Diseases: An Updated Systematic Review

Contact Info

Product

Resources

About