Infection of 5xFAD mice with a mouse‐adapted SARS‐CoV‐2 does not alter Alzheimer's disease neuropathology yet induces widespread changes in gene expression across diverse cell types

INTRODUCTION: The COVID-19 pandemic underscored the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on worsening the severity of Alzheimer's disease (AD) neuropathology and disease progression. METHODS: Aged 5xFAD and wild-type (WT) mice were infected with a mouse-adapted SARS-CoV-2 (MA10), and extensive characterization of molecular and cellular changes within the brains was carried out. RESULTS: MA10 infection induced acute viral pneumonia. Viral RNA was undetectable within the brains of infected mice, and there was no evidence of glial activation or neuroinflammation. MA10 infection did not affect amyloid beta (Aβ) plaque volume or numbers in 5xFAD mice compared to uninfected mice. Spatial transcriptomics revealed altered expression of genes associated with homeostatic function in neurons, glia, and vascular endothelial cells. DISCUSSION: Collectively, these findings demonstrate that while MA10 infection did not affect AD neuropathology, there were numerous downstream effects on gene expression associated with resident central nervous system cell functions that may impact neurologic disease.