SARS-CoV-2 Infects Neurons and Induces Neuroinflammation in a Non-Human Primate Model of COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the coronavirus disease 2019 (COVID-19), induces multiple neurological complications. However, it is still under debate if SARS-CoV-2 directly infects the brain, or if CNS sequelae result from inflammatory responses triggered by the virus systemically. Using high-resolution microscopy, we investigated whether SARS-CoV-2 reaches the brain, and how viral neurotropism can be modulated by aging in a nonhuman primate model of COVID-19. Seven days after infection, SARS-CoV-2 was detected in the olfactory cortex and interconnected regions, accompanied by robust neuroinflammation and neuronal damage, exacerbated in aged 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 reduce the burden of COVID-19 neurological complications.Funding Information: National Institute of Health grant 3RF1AG061001-01S1 (JHM, SSI). National Institute of Health grant R21 AI143454-02S1 (SSI). George Mason University – FAST grant (SSI). National Institute of Health grant P51OD011107 (KVR, JHM, SSI).Conflict of Interests: Authors declare that they have no competing interests.Ethical Approval: All study procedures were approved by the Institutional Animal Care and Use Committee at UC Davis.