Progress in Research on SARS-CoV-2 Infection Causing Neurological Diseases and Its Infection Mechanism

Wang, Lintao; Ren, Zhiguang; Ma, Li; Han, Yongtao; Wei, Wenqiang; Ji, Xin

doi:10.3389/fneur.2020.592888

Cited by 11 publications

(12 citation statements)

References 84 publications

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“…Although the great majority of people infected with SARS-CoV-2 develop only mild or asymptomatic disease, COVID-19 has already taken more than 5.7 million lives worldwide. Moreover, although it is essentially a lung disease, unconventional neurological symptoms have been reported since the beginning of the pandemic, from mild anosmia and ageusia 19,21 , to more severe neurological cases of encephalitis, cerebrovascular disease, ataxia and seizures 37 . Most recently, the description of the "long COVID-19" and the "brain fog", still intrigues physicians and researchers, as cases of cognitive impairment, memory impairment, disorientation and depression have been increasing, evidencing the complexity of the disease 27,38 .…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes

Oliveira

Angelo

Yamamoto

et al. 2021

Preprint

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Coronaviruses belong to a well-known family of enveloped RNA viruses and are the causative agent of the common cold. Although the seasonal coronaviruses do not pose a threat to human life, three members of this family, i.e., SARS-CoV, MERS-CoV and recently, SARS-CoV2, may cause severe acute respiratory syndrome and lead to death. Unfortunately, COVID-19 has already caused more than 4.4 million deaths worldwide. Although much is better understood about the immunopathogenesis of the lung disease, important information about systemic disease is still missing, mainly concerning neurological parameters. In this context, we sought to evaluate immunometabolic changes using in vitro and in vivo models of hamsters infected with SARS-CoV-2. Here we show that, besides infecting hamsters astrocytes, SARS-CoV-2 induces changes in protein expression and metabolic pathways involved in carbon metabolism, glycolysis, mitochondrial respiration, and synaptic transmission. Interestingly, many of the differentially expressed proteins are concurrent with proteins that correlate with neurological diseases, such as Parkinsons's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. Metabolic analysis by high resolution real-time respirometry evidenced hyperactivation of glycolysis and mitochondrial respiration. Further metabolomics analysis confirmed the consumption of many metabolites, including glucose, pyruvate, glutamine, and alpha ketoglutarate. Interestingly, we observed that glutamine was significantly reduced in infected cultures, and the blockade of mitochondrial glutaminolysis significantly reduced viral replication and pro-inflammatory response. SARS-CoV-2 was confirmed in vivo as hippocampus, cortex, and olfactory bulb of intranasally infected hamsters were positive for viral genome several days post-infection. Altogether, our data reveals important changes in overall protein expression, mostly of those related to carbon metabolism and energy generation, causing an imbalance in important metabolic molecules and neurotransmitters. This may suggest that some of the neurological features observed during COVID-19, as memory and cognitive impairment, may rely on altered energetic profile of brain cells, as well as an unbalanced glutamine/glutamate levels, whose importance for adequate brain function is unquestionable.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes

Oliveira

Angelo

Yamamoto

et al. 2021

Preprint

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“…But, many studies have also confirmed that ACE2 and TMPRSS2 may be expressed at low levels in the brain ( Rothan and Byrareddy, 2020 , Butowt and Bilinska, 2020 ), and the cell types include glial cells, neurons ( Wu et al, 2020 , Guo et al, 2020 ), and epithelial cells from the veins ( Jacob et al, 2020 ). ACE is expressed in the following brain regions: nucleus tractus solitarius, ventral region of the medulla oblongata, substantia nigra (SN), olfactory bulb (OB), ventricle, middle temporal gyrus, cingulate cortex, motor cortex, and other cerebral cortex areas ( Flores, 2021 , Wang et al, 2021 , Faried et al, 2020 ). Therefore, the virus should theoretically be able to infect nerve cells and possibly spread throughout the brain.…”

Section: How Does Sars-cov-2 Affect the Nervous System?mentioning

confidence: 99%

“…At the same time, the Angiotensin Type 1 receptor (AT1 receptor) is over-activated, and the level of angiotensin II increases ( Zou et al, 2020 ). Angiotensin II is a powerful angiotonics in capillary and arteriole vasoconstrictor, affecting blood pressure and cerebral blood flow regulation, and its increass may lead to cerebral hemorrhage and ischemic stroke ( Wang et al, 2021 ). ACE2 expression on endothelial cells is higher in COVID-19 patients with dementia and hypertension, and these patients have generally poorer prognosis ( Buzhdygan et al, 2020a ).…”

Section: How Does Sars-cov-2 Affect the Nervous System?mentioning

confidence: 99%

“…CSF's cytological and biochemical tests are similar to the characteristics of common viral encephalitis, manifested by mild protein and cell count abnormalities ( Moriguchi et al, 2020 , Huang et al, 2020b , Sun and Guan, 2020 ). It indicates that there may be other factors (such as peripheral infectious inflammation and neurotransmitter changes) that lead to meningoencephalitis ( Wang et al, 2021 ). In addition, the neurological prognosis of most patients with encephalitis or encephalopathy is generally favorable ( Wang et al, 2021 ).…”

Section: Nervous System Diseases Related To Sars-cov-2mentioning

confidence: 99%

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Nervous system manifestations related to COVID-19 and their possible mechanisms

Xie

Huang

Zhao

et al. 2022

Brain Research Bulletin

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“…11 The COVID-19 causative virus can cross the blood-brain barrier and invade the brain. 12 The SARS-CoV-2 virus enters the brain either via the olfactory system or the hematogenous route. 13 Endothelial cells on the cerebral vessels contain angiotensin-converting enzyme two receptors which are thought to be a possible viral entry point.…”

Section: Introductionmentioning

confidence: 99%

Neurological Manifestations of Covid-19 Hospitalized Patients In the state of Punjab, India

Parry

Bumb

Kumar³

et al. 2021

Bangladesh J Med Sci

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Introduction: COVID 19 often presents with flu-like symptoms. Elderly patients with systemic comorbidities are more likely to have severe COVID 19 infections and deaths. Severe neurological complications are frequently reported in severely and critically ill patients. In COVID-19, both central and peripheral nervous systems can be affected. The study aims to overview the spectrum, characteristics, and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: A total of 1000 confirmed CoVID-19 patients were enrolled for the study. Demographic features and initial clinical manifestations were noted, and patients were followed during the hospital stay to develop any new neurological signs and symptoms. For analytical purposes, neurological presentations were grouped into the central nervous system, peripheral nervous system, and musculoskeletal system manifestations. Appropriate laboratory testing was employed as required on a case-to-case basis. Results: The mean age was 44.6 ± 14.3 years. 625 (62.5%) patients were male, while 375 (37.5%) were female. The neurological illness was a primary manifestation in 119 (11.9%) cases. These included encephalopathy (n=78), ischemic stroke (n=28), Guillain- Barre syndrome, (n=3), facial nerve palsy (n=4), and encephalitis (n=6). The most common neurological symptoms were headache 313 (31.3%) and hyposmia 52 (5.2%), followed by encephalopathy 78 (7.8%). More serious complications like seizures 18 (1.8%) and stroke 28 (2.8%) were also seen. Conclusion: CoVID-19 can present with a neurological illness, and we should remain vigilant to the possibility of neurological presentation of COVID-19 that can be thrombo-embolic, inflammatory, or immune-mediated. Bangladesh Journal of Medical Science Vol.20(5) 2021 p.155-161

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Progress in Research on SARS-CoV-2 Infection Causing Neurological Diseases and Its Infection Mechanism

Cited by 11 publications

References 84 publications

SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes

SARS-CoV-2 Infection Impacts Carbon Metabolism and Depends on Glutamine for Replication in Syrian Hamster Astrocytes

Nervous system manifestations related to COVID-19 and their possible mechanisms

Neurological Manifestations of Covid-19 Hospitalized Patients In the state of Punjab, India

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