Spatial transcriptomics n the postmortem brains of severe acute COVID19 [midbrain]

Understanding the pathological basis of the neurological symptoms observed following SARS-CoV2 infection is essential to optimizing outcomes and developing therapeutics. To date, small sample sizes and narrow molecular profiling limit the generalizability of findings. We profiled multiple cortical and subcortical regions in postmortem COVID-19 patient brains and controls (total n=42) with spatial transcriptomics in the frontal cortex, midbrain and pons, bulk RNA expression in frontal cortex, midbrain, basal ganglia, and pons, and proteomics in the 8 regions (frontal cortex, temporal cortex, occipital cortex, midbrain, pons, hippocampus, thalamus and basal ganglia). We observed a multi-regional antiviral response in the absence of direct active SARS-CoV2 infection. We identified dysregulation of mitochondrial and synaptic pathways in deep-layer excitatory neurons and up-regulation of neuroinflammation in glia, in both mRNA and protein. Remarkably, these alterations overlapped substantially with changes in various age-related neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our work, combining multiple experimental and analytical methods, demonstrates the brain-wide impact of severe COVID-19, involving both cortical and subcortical regions, shedding light on potential therapeutic targets within pathways typically associated with pathological aging. The data presented here is a part of the Nanostring GeoMx DSP study. 319 ROIs are profiled. GeoMx DSP results of 79 ROIs in the midbrain (substaintia nigra, red nucleus, cerebral peduncle and periaqueduct grey matter) >>>Submitter states that raw data are not available due to patient privacy concerns.<<<