Neuroprotective Potential of Vaccination Against SARS-CoV-2 in Nonhuman Primates

This project will determine the temporal and anatomic profile of COVID-19 related changes in brain function and neurobiology and whether identified changes relate to brain alterations seen in Alzheimer's Disease (AD). Although COVID-19 is a novel coronavirus disease, studies have reported that brain structure and function is significantly impacted in humans who become infected and subsequently exhibit cognitive deficits. While it is unclear whether COVID-19 may be a causative or exacerbating factor for dementia, a recent study reported that AD-associated peripheral biomarkers such as t-tau, p-tau181, GFAP, and NfL were elevated in hospitalized COVID+ patients without a history of dementia. These markers correlated with severity of COVID-19 illness (Frontera et al., 2021). While many of the neurological symptoms seen in COVID-19 patients are also exhibited in AD patients, it remains unclear whether any of the markers were present prior to infection or changed because of infection. The ability to identify changes in brain function and neurobiological markers of neurodegeneration early in the COVID-19 disease process would help illuminate whether specific brain regions are more vulnerable than others to infection. Using a cross-sectional experimental design, we recently applied magnetoencephalography (MEG) in nonhuman primates to test the efficacy of a novel COVID vaccine to record resting state (RS) brain function in vaccinated and unvaccinated animals after infection with SARS-CoV-2 and found significant differences in brain function between the groups. We will extend these findings in vervet monkeys to record RS and sensory gating (SG) brain function PRIOR to vaccination and infection. Baseline brain activity will confirm whether any of the changes we detected in the cross-sectional study exist at baseline prior to vaccination and infection. We will measure RS and SG brain function AFTER vaccination with the Moderna mRNA vaccine or a novel psoralen inactivated virus and subsequent challenge with live virus. This will allow us to identify the temporal and anatomical profile of changes in brain activity that result from COVID infection early in the infection process. We will also collect biological samples including CSF and blood pre- and post-infection to track levels of peripheral biomarkers of neurodegenerative diseases that result from COVID infection. We will identify changes in RS and SG brain function to correlate changes in specific brain regions that underlie self-reports of cognitive deficits including 'foggy brain' and confusion related to "long COVID" that COVID+ patients report during the recovery period. We will utilize a simple bimanual coordination task as a behavioral measure with which to correlate changes in brain function and markers of neurodegeneration. The ability to capture baseline measures of brain function, behavioral measures and biomarkers prior to infection and vaccination and then early in the disease process will provide valuable insight into which brain regions and neurodegenerative markers may be most impacted by the disease process.