SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19
et al., Cell Reports, doi:10.1016/j.celrep.2022.111573, Nov 2022
Animal study (rhesus macaques) showing that SARS-CoV-2 directly infects neurons and induces neuroinflammation in olfactory brain regions within 7 days post-infection. SARS-CoV-2 nucleocapsid protein, spike protein, and dsRNA (marker of productive infection) were detected in the piriform cortex, olfactory tubercle, entorhinal cortex, and orbitofrontal cortex, with neurons being the primary site of productive infection.
Beckman et al., 30 Nov 2022, USA, peer-reviewed, 11 authors.
Contact: jhmorrison@ucdavis.edu (corresponding author), jhmorrison@ucdavis.edu (corresponding author).
Abstract: Check
SARS-CoV-2
Neurons
OFC
OB
PC
EC
SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19
Graphical abstract
Highlights
- d In macaques, SARS-CoV-2 is found in olfactory brain areas at 7 days post infection
- d Neurons are initially the primary target of SARS-CoV-2 productive infection
- d Neurocovid is accompanied by robust neuroinflammation and vascular disruption
- d SARS-CoV-2 brain pathology is worsened by aging and diabetes in infected monkeys
Authors
Danielle Beckman, Alyssa Bonillas, Giovanne B. Diniz, ..., Koen K.A. Van Rompay, Smita S. Iyer, John H. Morrison
Correspondence
[jhmorrison@ucdavis.edu](mailto:jhmorrison@ucdavis.edu)
In brief
Beckman et al. show that SARS-CoV-2 proteins are found in olfactory areas of the brains of rhesus macaques at 7 days post infection. In addition to direct neuronal infection, extensive neuroinflammation and vascular disruptions are observed, and these effects are exacerbated in aged, diabetic animals.
OT.
Report
SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19
Danielle Beckman, 1,6 Alyssa Bonillas, 1,6 Giovanne B. Diniz, 1 Sean Ott, 1 Jamin W. Roh, 2,3 Sonny R. Elizaldi, 2,3 Brian A. Schmidt, 2 Rebecca L. Sammak, 1 Koen K.A. Van Rompay, 1,4 Smita S. Iyer, 1,2,4 and John H. Morrison 1,5,7, *
1 California National Primate Research Center, University of California Davis, Davis, CA 95616, USA
2 Center for Immunology and Infectious Diseases, University of California Davis, Davis, CA 95616, USA
3 Graduate Group in Immunology, University of California Davis, Davis, CA 95616, USA
4 Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA
5 Department of Neurology, School of Medicine, University of California Davis, Davis, CA 95616, USA
6 These authors contributed equally
7 Lead contact
[*Correspondence: jhmorrison@ucdavis.edu](mailto:jhmorrison@ucdavis.edu)
[https://doi.org/10.1016/j.celrep.2022.111573](https://doi.org/10.1016/j.celrep.2022.111573)
SUMMARY
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.
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