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

• Published in: Cell reports (Cambridge) Vol. 41; no. 5; p. 111573
• Main Authors: Beckman, Danielle, Bonillas, Alyssa, Diniz, Giovanne B., Ott, Sean, Roh, Jamin W., Elizaldi, Sonny R., Schmidt, Brian A., Sammak, Rebecca L., Van Rompay, Koen K.A., Iyer, Smita S., Morrison, John H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2022; The Author(s)
• Subjects: Animals; astrocytes; coronavirus; COVID-19; macaque; microglia; Nervous System Diseases; Neuroinflammatory Diseases; Neurons; neurotropism; NHP; Primates; rhesus; SARS-CoV-2; neurotropism; macaque; rhesus; CP: Neuroscience; NHP; CP: Microbiology; coronavirus; astrocytes; microglia
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.111573

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. [Display omitted] •In macaques, SARS-CoV-2 is found in olfactory brain areas at 7 days post infection•Neurons are initially the primary target of SARS-CoV-2 productive infection•Neurocovid is accompanied by robust neuroinflammation and vascular disruption•SARS-CoV-2 brain pathology is worsened by aging and diabetes in infected monkeys 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.