Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System

Felice, Fernanda G. De; Tovar‐Moll, Fernanda; Moll, Jorge; Munoz, Douglas P.; Ferreira, Sérgio T.

doi:10.1016/j.tins.2020.04.004

Cited by 210 publications

(213 citation statements)

References 16 publications

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…However, emerging case reports showed that patients infected with SARS-CoV-2 suffered a sudden and complete loss of the olfactory function, stroke, and other severe neurological symptoms (Chen et al, 2020;Helms et al, 2020;Poyiadji et al, 2020;Sedaghat & Karimi, 2020;Virani et al, 2020). All of these indicate that SARS-CoV-2 could infect the central nervous system (CNS) and is therefore neurotropic (Baig et al, 2020;Conde Cardona et al, 2020;De Felice et al, 2020). Earlier studies show that SARS-CoV target the brains of mice, and since the different coronaviruses share a similar structure, it is likely that SARS-CoV-2 exhibits the same infection mechanism and possibly invades into the brain (McCray et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

SARS ‐CoV‐2 targets neurons of 3D human brain organoids

et al. 2020

View full text Add to dashboard Cite

COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Düsseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within 2 days of exposure. We identified that SARS-CoV-2 preferably targets neurons of brain organoids. Imaging neurons of organoids reveal that SARS-CoV-2 exposure is associated with altered distribution of Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Our studies, therefore, provide initial insights into the potential neurotoxic effect of SARS-CoV-2 and emphasize that brain organoids could model CNS pathologies of COVID-19.

show abstract

Section: Introductionmentioning

confidence: 99%

SARS ‐CoV‐2 targets neurons of 3D human brain organoids

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Various coronaviruses were shown to enter the cerebrospinal fluid (CSF) both in animal experiments and in patients with neurological symptoms ( De Felice et al, 2020 ). In addition, RNA of the SARS-CoV and of the current SARS-CoV2 were detected in the CSF of patients with neurological symptoms ( Hung et al, 2003 ; Moriguchi et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Histological Evidence for the Enteric Nervous System and the Choroid Plexus as Alternative Routes of Neuroinvasion by SARS-CoV2

et al. 2020

View full text Add to dashboard Cite

Evidence is mounting that the novel corona virus SARS-CoV2 inflicts neurological symptoms in a subgroup of COVID-19 patients. While plenty of theories on the route of neuroinvasion have been proposed, little histological evidence has been presented supporting any of these hypotheses. Therefore, we carried out immunostainings for ACE2 and TMPRSS2, two proteinases crucial for the entry of SARS-CoV2 into host cells, in the human enteric nervous system (ENS), as well as in the choroid plexus of the lateral ventricles. Both of these sites are important, yet often neglected entry gates to the nervous system. We found that ACE2 and TMPRSS2 are expressed by enteric neurons and glial cells of the small and large intestine, as well as choroid plexus epithelial cells, indicating that these cells meet the molecular requirements for viral entry. Together, our results are fundamental histological evidence substantiating current theories of neuroinvasion by SARS-CoV2.

show abstract

“…However, emerging case reports showed that patients infected with SARS-CoV-2 suffered a sudden and complete loss of the olfactory function, stroke, and other severe neurological symptoms (3)(4)(5)(6)(7). All of these indicate that SARS-CoV-2 is neurotropic and could infect the central nervous system (CNS) (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects

Gopalakrishnan

Ramani

Mueller

et al. 2020

Preprint

View full text Add to dashboard Cite

COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Düsseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within two days of exposure. Using COVID-19 convalescent serum, we identified that SARS-CoV-2 preferably targets soma of cortical neurons but not neural stem cells, the target cell type of ZIKA virus. Imaging cortical neurons of organoids reveal that SARS-CoV-2 exposure is associated with missorted Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Surprisingly, SARS-CoV-2 co-localizes specifically with Tau phosphorylated at Threonine-231 in the soma, indicative of early neurodegeneration-like effects. Our studies, therefore, provide initial insights into the impact of SARS-CoV-2 as a neurotropic virus and emphasize that brain organoids could model CNS pathologies of COVID-19.

show abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System

Cited by 210 publications

References 16 publications

SARS ‐CoV‐2 targets neurons of 3D human brain organoids

SARS ‐CoV‐2 targets neurons of 3D human brain organoids

Histological Evidence for the Enteric Nervous System and the Choroid Plexus as Alternative Routes of Neuroinvasion by SARS-CoV2

SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects

Contact Info

Product

Resources

About