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

Cell Rep. 2022 Nov 1;41(5):111573. doi: 10.1016/j.celrep.2022.111573. Epub 2022 Oct 12.

Authors

Affiliations

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; Graduate Group in Immunology, University of California Davis, Davis, CA 95616, USA.
³ Center for Immunology and Infectious Diseases, University of California Davis, Davis, CA 95616, USA.
⁴ California National Primate Research Center, University of California Davis, Davis, CA 95616, USA; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.
⁵ California National Primate Research Center, University of California Davis, Davis, CA 95616, USA; Center for Immunology and Infectious Diseases, University of California Davis, Davis, CA 95616, USA; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA.
⁶ California National Primate Research Center, University of California Davis, Davis, CA 95616, USA; Department of Neurology, School of Medicine, University of California Davis, Davis, CA 95616, USA. Electronic address: jhmorrison@ucdavis.edu.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
COVID-19*
Nervous System Diseases*
Neuroinflammatory Diseases
Neurons
Primates
SARS-CoV-2

Abstract

Publication types

MeSH terms

Grants and funding