Severe acute respiratory syndrome coronavirus 2 may be an underappreciated pathogen of the central nervous system

Alam, Syed Benazir; Willows, Steven; Kulka, Marianna; Sandhu, Jagdeep K.

doi:10.1111/ene.14442

Cited by 57 publications

(72 citation statements)

References 124 publications

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“…There are strong pieces of evidence of the neurotropism of coronaviruses, most of them based on the clinical manifestations, although it has not been completely elucidated how SARS-CoV-2 accesses the human CNS (for further review on this topic see ( Alam et al., 2020 ; Dos Santos et al., 2020 ; Fotuhi et al., 2020 ). Two hypotheses to explain SARS-CoV-2 neuroinvasion have been proposed so far ( Fig.…”

Section: Coronaviruses Sars-cov-2 and The Central Nervous Systemmentioning

confidence: 99%

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and glial cells: Insights and perspectives

Vargas

Geraldo

Salomão

et al. 2020

Brain, Behavior, & Immunity - Health

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In December 2019, a pneumonia outbreak was reported in Wuhan, Hubei province, China. Since then, the World Health Organization declared a public health emergency of international concern due to a growing number of deaths around the globe, as well as unparalleled economic and sociodemographic consequences. The disease called coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel form of human coronavirus. Although coronavirus infections have been associated with neurological manifestations such as febrile seizures, convulsions, change in mental status, and encephalitis, less is known about the impact of SARS-CoV-2 in the brain. Recently, emerging evidence suggests that SARS-CoV-2 is associated with neurological alterations in COVID-19 patients with severe clinical manifestations. The molecular and cellular mechanisms involved in this process, as well as the neurotropic and neuroinvasive properties of SARS-CoV-2, are still poorly understood. Glial cells, such as astrocytes and microglia, play pivotal roles in the brain response to neuroinflammatory insults and neurodegenerative diseases. Further, accumulating evidence has shown that those cells are targets of several neurotropic viruses that severely impact their function. Glial cell dysfunctions have been associated with several neuroinflammatory diseases, suggesting that SARS-CoV-2 likely has a primary effect on these cells in addition to a secondary effect from neuronal damage. Here, we provide an overview of these data and discuss the possible implications of glial cells as targets of SARS-CoV-2. Considering the roles of microglia and astrocytes in brain inflammatory responses, we shed light on glial cells as possible drivers and potential targets of therapeutic strategies against neurological manifestations in patients with COVID-19. The main goal of this review is to highlight the need to consider glial involvement in the progression of COVID-19 and potentially include astrocytes and microglia as mediators of SARS-CoV-2-induced neurological damage.

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Section: Coronaviruses Sars-cov-2 and The Central Nervous Systemmentioning

confidence: 99%

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and glial cells: Insights and perspectives

Vargas

Geraldo

Salomão

et al. 2020

Brain, Behavior, & Immunity - Health

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“…A mounting body of reports from SARS-CoV-2affected patients is showing that about 30% to 40% of patients develop serious central nervous system (CNS) symptoms, with neurological and neuroradiological alterations confirmed in a large number of cases (Alam et al, 2020;Helms et al, 2020;Jasti et al, 2020;Kremer et al, 2020;Mao et al, 2020;Najjar et al, 2020;Pryce-Roberts et al, 2020;Roma´n et al, 2020;Romero-Sa´nchez et al, 2020;Xiong et al, 2020; and several others). Plasma biomarkers of CNS injury have been shown to be increased in a group of patients with moderate and severe COVID-19 disease (Kanberg et al, 2020).…”

mentioning

confidence: 99%

Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

2020

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With confirmed coronavirus disease 2019 (COVID-19) cases surpassing the 18 million mark around the globe, there is an imperative need to gain comprehensive understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are associated with respiratory or intestinal symptoms, reports of neurological signs and symptoms are increasing. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the central nervous system (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood–brain barrier. Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS rennin-angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for Middle East respiratory syndrome coronavirus (MERS-CoV). Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes, and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to disbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this comprehensive review, we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV; explore the potential role for astrocytes and microglia in the infection and neuroinflammation; and compare them with the previously described human and animal CoV that showed neurotropism to propose possible underlying mechanisms.

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“…This BPA-induced increase in the density of TMPRSS2 immunoreactive cells in the medial amygdala of neonatal male rats suggests that BPA has the potential to disturb central nervous system (CNS) and neurodevelopmental processes [ 96 ]. Interestingly, increasing attention is now placed on the neurotropism of coronaviruses, such as SARS-CoV-2, and their potential effects on neuropathogenesis and the CNS [ 97 , 98 ].…”

Section: Bpa and Key Molecular Targets Of Sars-cov-2mentioning

confidence: 99%

Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

Zahra

Sisu

Silva

et al. 2020

JCM

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Infection by the severe acute respiratory syndrome (SARS) coronavirus-2 (SARS-CoV-2) is the causative agent of a new disease (COVID-19). The risk of severe COVID-19 is increased by certain underlying comorbidities, including asthma, cancer, cardiovascular disease, hypertension, diabetes, and obesity. Notably, exposure to hormonally active chemicals called endocrine-disrupting chemicals (EDCs) can promote such cardio-metabolic diseases, endocrine-related cancers, and immune system dysregulation and thus, may also be linked to higher risk of severe COVID-19. Bisphenol A (BPA) is among the most common EDCs and exerts its effects via receptors which are widely distributed in human tissues, including nuclear oestrogen receptors (ERα and ERβ), membrane-bound oestrogen receptor (G protein-coupled receptor 30; GPR30), and human nuclear receptor oestrogen-related receptor gamma. As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators. Overall, the potential role of BPA on the risk and severity of COVID-19 merits further investigation.

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Severe acute respiratory syndrome coronavirus 2 may be an underappreciated pathogen of the central nervous system

Cited by 57 publications

References 124 publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and glial cells: Insights and perspectives

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and glial cells: Insights and perspectives

Severe Acute Respiratory Syndrome Coronavirus 2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

Is There a Link between Bisphenol A (BPA), a Key Endocrine Disruptor, and the Risk for SARS-CoV-2 Infection and Severe COVID-19?

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