Since the start of the COVID-19 pandemic, clinical reports have indicated a number of cognitive and psychiatric symptoms which persist after the virus has been cleared from the host, termed post-acute sequel of SARS-CoV-2 (PASC; aka long COVID), where multiple neurological symptoms are observed, most commonly, brain-fog.  We have developed a preclinical model (5xFAD x hACE2 mice) which recapitulates key neuropathologies associated with PASC / brain fog, and have discovered significant microglial activation SARS-CoV-2 infected mice, as well as significant differential regulation of pathways key to leukocyte migration, BBB integrity, and synaptogenesis (figure). Our goal is to build on this data to help determine the mechanisms that drive neurological symptoms seen in PASC, as well as long term ramifications in response to infection and aging.