SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19

Danielle Beckman; Alyssa Bonillas; Giovanne B. Diniz; Sean Ott; Jamin W. Roh; Sonny R. Elizaldi; Brian A. Schmidt; Rebecca L. Sammak; Koen K.A. Van Rompay; Smita S. Iyer; John H. Morrison

doi:10.1016/j.celrep.2022.111573

SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19

Danielle Beckman, Alyssa Bonillas, Giovanne B. Diniz, Sean Ott, Jamin W. Roh, Sonny R. Elizaldi, Brian A. Schmidt, Rebecca L. Sammak, Koen K.A. Van Rompay, Smita S. Iyer, John H. Morrison

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can induce a plethora of neurological complications in some patients. However, it is still under debate whether SARS-CoV-2 directly infects the brain or whether CNS sequelae result from systemic inflammatory responses triggered in the periphery. By using high-resolution microscopy, we investigated whether SARS-CoV-2 reaches the brain and how viral neurotropism can be modulated by aging in a non-human primate model of COVID-19. Seven days after infection, SARS-CoV-2 was detected in the olfactory cortex and interconnected regions and was accompanied by robust neuroinflammation and neuronal damage exacerbated in aged, diabetic animals. Our study provides an initial framework for identifying the molecular and cellular mechanisms underlying SARS-CoV-2 neurological complications, which will be essential to reducing both the short- and long-term burden of COVID-19.

Original language	English
Article number	111573
Journal	Cell Reports
Volume	41
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2022.111573
State	Published - 1 Nov 2022
Externally published	Yes

Keywords

CP: Microbiology
CP: Neuroscience
NHP
astrocytes
coronavirus
macaque
microglia
neurotropism
rhesus

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10.1016/j.celrep.2022.111573

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title = "SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19",

abstract = "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can induce a plethora of neurological complications in some patients. However, it is still under debate whether SARS-CoV-2 directly infects the brain or whether CNS sequelae result from systemic inflammatory responses triggered in the periphery. By using high-resolution microscopy, we investigated whether SARS-CoV-2 reaches the brain and how viral neurotropism can be modulated by aging in a non-human primate model of COVID-19. Seven days after infection, SARS-CoV-2 was detected in the olfactory cortex and interconnected regions and was accompanied by robust neuroinflammation and neuronal damage exacerbated in aged, diabetic animals. Our study provides an initial framework for identifying the molecular and cellular mechanisms underlying SARS-CoV-2 neurological complications, which will be essential to reducing both the short- and long-term burden of COVID-19.",

keywords = "CP: Microbiology, CP: Neuroscience, NHP, astrocytes, coronavirus, macaque, microglia, neurotropism, rhesus",

author = "Danielle Beckman and Alyssa Bonillas and Diniz, {Giovanne B.} and Sean Ott and Roh, {Jamin W.} and Elizaldi, {Sonny R.} and Schmidt, {Brian A.} and Sammak, {Rebecca L.} and {Van Rompay}, {Koen K.A.} and Iyer, {Smita S.} and Morrison, {John H.}",

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doi = "10.1016/j.celrep.2022.111573",

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AU - Beckman, Danielle

AU - Bonillas, Alyssa

AU - Diniz, Giovanne B.

AU - Ott, Sean

AU - Roh, Jamin W.

AU - Elizaldi, Sonny R.

AU - Schmidt, Brian A.

AU - Sammak, Rebecca L.

AU - Van Rompay, Koen K.A.

AU - Iyer, Smita S.

AU - Morrison, John H.

PY - 2022/11/1

Y1 - 2022/11/1

N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can induce a plethora of neurological complications in some patients. However, it is still under debate whether SARS-CoV-2 directly infects the brain or whether CNS sequelae result from systemic inflammatory responses triggered in the periphery. By using high-resolution microscopy, we investigated whether SARS-CoV-2 reaches the brain and how viral neurotropism can be modulated by aging in a non-human primate model of COVID-19. Seven days after infection, SARS-CoV-2 was detected in the olfactory cortex and interconnected regions and was accompanied by robust neuroinflammation and neuronal damage exacerbated in aged, diabetic animals. Our study provides an initial framework for identifying the molecular and cellular mechanisms underlying SARS-CoV-2 neurological complications, which will be essential to reducing both the short- and long-term burden of COVID-19.

AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can induce a plethora of neurological complications in some patients. However, it is still under debate whether SARS-CoV-2 directly infects the brain or whether CNS sequelae result from systemic inflammatory responses triggered in the periphery. By using high-resolution microscopy, we investigated whether SARS-CoV-2 reaches the brain and how viral neurotropism can be modulated by aging in a non-human primate model of COVID-19. Seven days after infection, SARS-CoV-2 was detected in the olfactory cortex and interconnected regions and was accompanied by robust neuroinflammation and neuronal damage exacerbated in aged, diabetic animals. Our study provides an initial framework for identifying the molecular and cellular mechanisms underlying SARS-CoV-2 neurological complications, which will be essential to reducing both the short- and long-term burden of COVID-19.

KW - CP: Microbiology

KW - CP: Neuroscience

KW - NHP

KW - astrocytes

KW - coronavirus

KW - macaque

KW - microglia

KW - neurotropism

KW - rhesus

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DO - 10.1016/j.celrep.2022.111573

M3 - Article

AN - SCOPUS:85140445227

SN - 2211-1247

VL - 41

JO - Cell Reports

JF - Cell Reports

IS - 5

M1 - 111573

ER -

SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19

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Keywords

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