Abstract
The coronavirus disease 2019 (COVID‐19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused more than 6.3 million deaths worldwide. Recent evidence has indicated that elderly people with dementia are particularly vulnerable to COVID‐19 and severe disease outcomes. However, its molecular mechanism remains largely unknown. Here, we retrieved frontal cortex samples of COVID‐19 patients from the Gene Expression Omnibus (GEO) database and performed a systematic transcriptomic analysis to compare COVID‐19 patients and controls with or without dementia. In nondemented patients, SARS‐CoV‐2 infection obviously activated T helper type 2 (Th2) cell‐mediated humoral immunity and reduced the pathogenesis of dementia‐related Alzheimer's disease and Parkinson's disease. In demented patients, conversely, SARS‐CoV‐2 infection significantly increased Th1 cell‐mediated cellular immunity and exacerbated the progression of dementia‐related diseases. We further analyzed the molecular characteristics of COVID‐19 patients with and without dementia. Compared with nondemented COVID‐19 patients, demented COVID‐19 patients showed decreased enrichment scores of Calcium signaling pathway, Neuroactive ligand‐receptor interaction, ABC transporters and Peroxisome, and increased enrichment scores of Olfactory transduction and Regulation of autophagy. The ratio of Th1/Th2 cells was significantly increased from 1.17 in nondemented COVID‐19 patients to 33.32 in demented COVID‐19 patients. Taken together, our findings provide transcriptomic evidence that COVID‐19 has distinct influences on cognitive function and immune response in patients with and without dementia.
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Keywords: Alzheimer's disease, COVID‐19, dementia, immune response, SARS‐CoV‐2