Whole-transcriptome sequencing data reveals a disparate cognitive and immune signature in COVID-19 patients with and without dementia.

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 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 T helper type 1 (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.