Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment

Zhou, Yadi; Xu, Jielin; Hou, Yuan; Leverenz, James B.; Kallianpur, Asha R.; Mehra, Reena; Liu, Yunlong; Yu, Haiyuan; Pieper, Andrew A.; Jehi, Lara; Cheng, Feixiong

doi:10.1186/s13195-021-00850-3

Cited by 112 publications

(57 citation statements)

References 125 publications

(200 reference statements)

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“…Likewise, hsa-miR-298 can bind the 5′UTR region, and its down-regulation in Alzheimer disease has been demonstrated. According to previously published papers, the binding of miRNAs to the viral genome may reduce the levels of free miRNAs in the cell, and it has been recently reported that COVID patients may develop an Alzheimer’s-like disease [ 51 ]. Moreover, the ability of hsa-miR-3941 to target the SARS-CoV-2 3′-UTR was recently validated in vitro by gene reporter assays [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-Mediated Regulation of the Virus Cycle and Pathogenesis in the SARS-CoV-2 Disease

Battaglia

Alonzo

Pennisi

et al. 2021

IJMS

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In the last few years, microRNA-mediated regulation has been shown to be important in viral infections. In fact, viral microRNAs can alter cell physiology and act on the immune system; moreover, cellular microRNAs can regulate the virus cycle, influencing positively or negatively viral replication. Accordingly, microRNAs can represent diagnostic and prognostic biomarkers of infectious processes and a promising approach for designing targeted therapies. In the past 18 months, the COVID-19 infection from SARS-CoV-2 has engaged many researchers in the search for diagnostic and prognostic markers and the development of therapies. Although some research suggests that the SARS-CoV-2 genome can produce microRNAs and that host microRNAs may be involved in the cellular response to the virus, to date, not enough evidence has been provided. In this paper, using a focused bioinformatic approach exploring the SARS-CoV-2 genome, we propose that SARS-CoV-2 is able to produce microRNAs sharing a strong sequence homology with the human ones and also that human microRNAs may target viral RNA regulating the virus life cycle inside human cells. Interestingly, all viral miRNA sequences and some human miRNA target sites are conserved in more recent SARS-CoV-2 variants of concern (VOCs). Even if experimental evidence will be needed, in silico analysis represents a valuable source of information useful to understand the sophisticated molecular mechanisms of disease and to sustain biomedical applications.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-Mediated Regulation of the Virus Cycle and Pathogenesis in the SARS-CoV-2 Disease

Battaglia

Alonzo

Pennisi

et al. 2021

IJMS

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“…In the COVID-19, it is highly likely that impaired retinoid signaling has an important role in the development of in the nervous system-related symptoms [170] , [171] .In the course of COVID-19, the involvement of these areas of the nervous system where retinoid signaling is normally highly intense, may likely suggest a cause-and-effect association that needs further investigation. In addition to the mild symptoms and severe clinical picture of acute illness, neuropsychiatric manifestations such as autism, dementia, schizophrenia, depression, and insomnia may occur as post-COVID syndromes that can well be, at least partially, due to impaired retinoid signaling [172] , [173] .…”

Section: Cns Involvement and Retinoid Signaling Disorder Incovid-19mentioning

confidence: 99%

A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder

Sarohan¹,

Kızıl

İnkaya

et al. 2021

Cellular Signalling

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The SARS-CoV-2 virus has caused a worldwide COVID-19 pandemic. In less than a year and a half, more than 200 million people have been infected and more than four million have died. Despite some improvement in the treatment strategies, no definitive treatment protocol has been developed. The pathogenesis of the disease has not been clearly elucidated yet. A clear understanding of its pathogenesis will help develop effective vaccines and drugs. The immunopathogenesis of COVID-19 is characteristic with acute respiratory distress syndrome and multiorgan involvement with impaired Type I interferon response and hyperinflammation. The destructive systemic effects of COVID-19 cannot be explained simply by the viral tropism through the ACE2 and TMPRSS2 receptors. In addition, the recently identified mutations cannot fully explain the defect in all cases of Type I interferon synthesis. We hypothesize that retinol depletion and resulting impaired retinoid signaling play a central role in the COVID-19 pathogenesis that is characteristic for dysregulated immune system, defect in Type I interferon synthesis, severe inflammatory process, and destructive systemic multiorgan involvement. Viral RNA recognition mechanism through RIG-I receptors can quickly consume a large amount of the body's retinoid reserve, which causes the retinol levels to fall below the normal serum levels. This causes retinoid insufficiency and impaired retinoid signaling, which leads to interruption in Type I interferon synthesis and an excessive inflammation. Therefore, reconstitution of the retinoid signaling may prove to be a valid strategy for management of COVID-19 as well for some other chronic, degenerative, inflammatory, and autoimmune diseases.

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“…Several studies have described the presence of brain lesions as responsible of auditory impairment ( 9 – 11 ), supporting the hypothesis that SARS-CoV-2, which has neuro-invasive characteristics, might determine a central hearing loss in COVID-19 patients both in the active phase and during recovery ( 12 ). It has been shown that the virus can spread from neuroepithelium to the olfactory bulb to the brain ( 13 – 15 ), causing loss of smell ( 16 ), persistent cough after pneumonia resolution ( 17 ), memory deficit ( 18 ), and neurocognitive problems ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Auditory Disturbances and SARS-CoV-2 Infection: Brain Inflammation or Cochlear Affection? Systematic Review and Discussion of Potential Pathogenesis

et al. 2021

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Patients affected by COVID-19 present a series of different symptoms; despite some of these are common, other less likely appear. Auditory symptoms seem to be less frequent, maybe because rarer or, alternatively, because they are underestimated during the clinical investigation. The hearing impairment might be related to the central or peripheral involvement of the auditory pathways; in particular, the likelihood of thrombosis might be one of the causes. To date, the prevalence of auditory symptoms such as sudden or progressive sensorineural hearing loss and tinnitus is unclear in COVID-19 patients. However, their presence might be an early sign of thrombosis or spread of the infection into the brain. In this systematic review of the literature we investigated the presence of auditory symptoms in COVID-19 patients and discussed their potential origin and causal relationship with SARS-CoV-2. Results showed that, despite rarely, auditory impairment can appear in patients with COVID-19 and should always be investigated for an early treatment and potential indicator of involvement of the central nervous system.

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Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment

Cited by 112 publications

References 125 publications

MicroRNA-Mediated Regulation of the Virus Cycle and Pathogenesis in the SARS-CoV-2 Disease

MicroRNA-Mediated Regulation of the Virus Cycle and Pathogenesis in the SARS-CoV-2 Disease

A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder

Auditory Disturbances and SARS-CoV-2 Infection: Brain Inflammation or Cochlear Affection? Systematic Review and Discussion of Potential Pathogenesis

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