SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19, 2022, Beckman et al

[Hutan]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554328/
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.

 

[Hutan]

I think this abstract rather obscures the significant finding of brain infection in both young healthy and older diabetic monkeys. We've seen brain infection also reported from postmortem studies of human brains.

This study is explained in this readable article:
SARS-CoV-2 causes neuronal damage and inflammation within a week of infection in rhesus macaques

We not only demonstrated that the virus infects the brain, but also that it directly infects neurons and can be transported along nerve pathways to sites beyond the initial olfactory regions.

Young, healthy rhesus macaques and aged animals with Type 2 diabetes were inoculated with the SARS-Cov-2 virus and compared to noninfected, age-matched controls. Seven days after the animals were exposed to the virus, researchers were able to identify the virus in brain tissue as well as several different types of brain cell. High-powered microscopes allowed the scientists to visualize interactions between the virus and brain cells.

The researchers also aimed to understand how the virus could cause cell damage and lasting impacts on the brain. Evidence suggests that SARS-CoV-2 causes inflammation in the brain. Cells in the central nervous system respond by breaking down and removing the inflamed cells.

"Although this process can be beneficial and is meant to heal the central nervous system, the intensity with which SARS-CoV-2 induced inflammation in aged rhesus macaques led to significant damage," Beckman said.

The researchers are now studying the brains from monkeys several months after infection to better understand the extent and nature of brain damage that might underlie the long-term neurological complications of COVID-19.

Parts of the work were presented at the annual meeting of the Society for Neuroscience last year. Additional authors on the paper are: Alyssa Bonillas, Giovanne Diniz, Sean Ott, Jamin Roh, Sonny Elizaldi, Brian Schmidt, Rebecca Sammak, Koen Van Rompay and Smita Iyer, all at UC Davis. The work was supported by grants from the National Institutes of Health.

So, my interpretation of this is that the viral infection caused brain damage, making the similarities between some post-viral conditions with traumatic brain injury understandable, and making sense of the increased rates of diagnosis of dementia and cognitive difficulties that have been found in analyses of big medical records databases.

I think this team is one to watch, to see what they make of longer term impacts of covid-19 on the monkeys.

 

[Creekside]

I can imagine that this sort of viral infection of brain cells could induce the same mechanisms that cause ME symptoms. ME might involve a feedback loop causing glial cells to malfunction, and the response to a virus might cause a similar malfunction.

My recommendation to that team would be to investigate how the glial cells are reacting to those infected neurons.