Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders

Onisiforou, Anna; Spyrou, George M.

doi:10.3390/v14102270

Cited by 7 publications

(13 citation statements)

References 135 publications

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“…Some neurological conditions have also been linked to COVID-19 severity [ 201 , 280 , 407 ]. Possible mechanisms include immunosenescence, heightened IFN responses or genetic predisposition to severe COVID-19 (OAS1, APOE ε4 allele) in Alzheimer’s disease [ 350 , 408 , 409 , 410 ], respiratory muscle rigidity and insufficient cough reflex in Parkinson’s disease [ 350 , 411 ], systemic inflammation in epilepsy (with much uncertainty) [ 362 , 412 ] and susceptibility to acute stress in cerebrovascular diseases [ 413 , 414 ].…”

Section: Host Factorsmentioning

confidence: 99%

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Zsichla

Müller

2023

Viruses

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The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease and death. Understanding the risk factors of severe COVID-19 is relevant both in the clinical setting and at the epidemiological level. Here, we provide an overview of host, viral and environmental factors that have been shown or (in some cases) hypothesized to be associated with severe clinical outcomes. The factors considered in detail include the age and frailty, genetic polymorphisms, biological sex (and pregnancy), co- and superinfections, non-communicable comorbidities, immunological history, microbiota, and lifestyle of the patient; viral genetic variation and infecting dose; socioeconomic factors; and air pollution. For each category, we compile (sometimes conflicting) evidence for the association of the factor with COVID-19 outcomes (including the strength of the effect) and outline possible action mechanisms. We also discuss the complex interactions between the various risk factors.

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Section: Host Factorsmentioning

confidence: 99%

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Zsichla

Müller

2023

Viruses

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“…To generate the integrated networks, we merged the virus-host PPI network of each viral species with the AD PPI network, which consisted of the top 200 disease-associated proteins of AD. The confidence cut-off score, involving the interactions between the human proteins was set at 0.8, as in our previous works [23,28]. The confidence score is determined based on the nature and quality of the supporting evidence for the PPIs, with values ranging from 0 (indicating low confidence) to 1.0 (indicating high confidence).…”

Section: Methodsmentioning

confidence: 99%

“…Computational approaches, especially network-based methodologies, have been widely employed to shed light on microbe-host interactions underlying the onset of an array of diseases [25,26]. We have previously developed and applied innovative network-based approaches that allowed us to gain new insight on the role of existing viruses, but also emerging viruses (such as SARS-CoV-2), in the development of NDs [23,27,28]. In this study, we extend our previous research [23,27,28] to investigate viral-mediated pathogenic mechanisms that might lead to AD through virus-host protein-protein interactions (PPIs), with a focus on specific viral species (HSV-1, SARS-CoV-2, EBV, HCV, HCMV, Kaposi Sarcomaassociated Herpesvirus (KSHV), Hepatitis B Virus (HBV) and Influenza A virus (IAV)).…”

Section: Introductionmentioning

confidence: 99%

“…This reactivation may contribute to COVID-19 severity and post COVID-19 cognitive symptoms resembling AD, like memory impairment and brain fog [16,[19][20][21][22]. Our previous work, leveraging systems bioinformatics methodologies, also suggested an elevated risk of AD development following SARS-CoV-2 infection [23]. Hence, it is not surprising that there was an observed approximately 17% increase in AD-related deaths in 2020, possibly associated with COVID-19 infections [24].…”

Section: Introductionmentioning

confidence: 99%

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From Viral Infections to Alzheimer’s Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics

Onisiforou,

Zanos

2023

Preprint

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BackgroundEmerging evidence suggests that certain microorganisms, including viral infections, may contribute to the onset and/or progression of Alzheimer’s Disease (AD), a neurodegenerative condition characterized by memory impairment and cognitive decline. However, the precise extent of their involvement and the underlying mechanisms through which specific viruses increase AD susceptibility risk remain elusive.MethodsWe used an integrative systems bioinformatics approach to identity viral-mediated pathogenic mechanisms by which specific viral species, namely Herpes Simplex Virus 1 (HSV-1), Human Cytomegalovirus (HCMV), Epstein-Barr Virus (EBV), Kaposi Sarcoma-associated Herpesvirus (KSHV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Influenza A virus (IAV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), could facilitate the pathogenesis of AD via virus-host protein-protein interactions (PPIs). We also sought to uncover potential synergistic pathogenic effects resulting from the reactivation of specific herpesviruses (HSV-1, HCMV and EBV) during acute SARS-CoV-2 infection, potentially increasing AD susceptibility.ResultsOur findings show thatHerpesviridaeFamily members (HSV-1, EBV, KSHV, HCMV) impact AD-related processes like amyloid-beta formation, neuronal death, and autophagy. Hepatitis viruses (HBV, HCV) influence processes crucial for cellular homeostasis and dysfunction. Importantly, hepatitis viruses affect microglia activation via virus-host PPIs. Reactivation of HCMV during SARS-CoV-2 infection could potentially foster a lethal interplay of neurodegeneration, via synergistic pathogenic effects on AD-related processes like response to unfolded protein, regulation of autophagy, response to oxidative stress and amyloid-beta formation.ConclusionsCollectively, these findings underscore the complex link between viral infections and AD development. Perturbations in AD-related processes by viruses can arise from both shared and distinct mechanisms among viral species in different categories, potentially influencing variations in AD susceptibility.

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“…Other network and bioinformatics-based approaches conducted in HD include Sneha et al [132], Pirhaji et al [133], Pradhan et al [134], Xiang et al [135], Zaho et al [136], Fu et al [137], Shirasaki et al [138], Christodoulou [139][140][141], and Onisiforou [142].…”

Section: Network-based Approachesmentioning

confidence: 99%

Omics and Network-based Approaches in Understanding HD Pathogenesis

C. Christodoulou,

Zamba Papanicolaou

2024

Rare Neurodegenerative Disorders - New Insights [Working Title]

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Huntington’s Disease (HD) is a rare, progressive neurodegenerative disease caused by CAG repeat expansion in the Huntingtin gene. HD is an incurable disease; therefore, there is a growing need for effective therapeutic treatments and candidate biomarkers for prognosis and diagnosis of HD. Technological advancements over the past couple of years, have led to high-throughput experiments and omics data. The use of System Bioinformatics (SB) approaches, allows for the integration of information across different -omics, this can clarify synergistic relationships across biological molecules, resulting in complex biological networks. SB and network-based approaches, are able to shed light on the potential interactions of genes, proteins, metabolites and pathways participating in HD pathogenesis and how dysregulation of these biological entities, can affect age on onset, disease severity and progression. Moreover, −omics data analysis and network-based approaches can provide better understanding how these biological molecules interact with each other and provides potential drug targets and biomarkers that can be used to treat HD or delay symptom onset; therefore, opening the door towards precision medicine. The aim of the following chapter, is to discuss the most popular -omics related to HD research, and the growing popularity of single cell analysis, repositories and software available for bulk and single cell analysis. In addition, network-based approaches regarding HD will also be mentioned.

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Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders

Cited by 7 publications

References 135 publications

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

From Viral Infections to Alzheimer’s Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics

Omics and Network-based Approaches in Understanding HD Pathogenesis

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