Recapitulation of pathophysiological features of AD in SARS-CoV-2 infected subjects
Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimer's disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases. Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1a is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD. Overall design: Brain tissue was collected from the cortical BA9 and HF of four COVID_ADneg cases, four CONTROL ADpos and four COVID_ADpos and four CONTROL_ADneg autopsies. Tissue was collected in accordance with IRB-approved guidelines and regulations by the Brain Bank at Mount Sinai, and clinical data  including cardiovascular and neurological conditions were collected by the Department of Neurology. Samples collected and homogenized  to collect total RNA and generation of cDNA libraries for RNA sequencing study.