Neuropathology of SARS-CoV-2 Infection in Aged Non-human Primates

Neurological manifestations, including headache, altered mental status, and stroke, are a major complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and coronavirus disease-19 (COVID-19). In addition, continued neurological difficulties, such as impaired memory and attention or difficulty finding or understanding words, are often reported by individuals suffering from post-acute sequalae of COVID-19 (PASC) or “long COVID”. Understanding how SARS-CoV-2 effects the brain of infected patients is critical for appropriate treatment of infected patients, as well as initiating relevant follow-up care after recovery. Through our investigation of brain from SARS-CoV-2 infected non-human primates (NHPs), we found significant neuropathology that is consistent with that reported among human patients. Similar to humans, pathology was variable but included wide-spread neuroinflammation, nodular lesions, neuronal death, and microhemorrhages. Importantly, this was seen among infected animals that did not develop severe respiratory disease. Sparse virus was detected in brain endothelial cells but did not associate with the severity of CNS injury. These findings reveal SARS-CoV-2-associated neuropathology that has advanced our current understanding of how SARS-CoV-2 infection effects the brain. Furthermore, this work demonstrates SARS-CoV-2 infected NHPs are a highly relevant animal model for investigating COVID-19 neuropathogenesis among human subjects.

Learning Objectives:

1. Describe the variable neurological manifestations of SARS-CoV-2 infection.

2. Describe the neuropathology in brain of relevant non-human primate models of SARS-CoV-2 infection.

3. List important risk factors predisposing patients to neurological injury in the context of SARS-CoV-2 infection.