Fig. 1

A diagram illustrating a network-based, multimodal omics analytic framework. We examined the transcriptomes (both bulk and single-cell or single-nucleus) of patients with COVID-19 (blood and cerebrospinal fluid [CSF] samples) or Alzheimer’s disease (AD) (brain samples). We also compiled ten SARS-CoV-2 host (human) factor datasets based on CRISPR-Cas9 assays or protein-protein interaction assays, AD blood and CSF markers, and neurological disease-associated genes/proteins. Using network proximity analysis in the human protein-protein interactome, we investigated network-based associations between SARS-CoV-2 host factors and several selected neurological diseases. To understand the potential mechanisms through which SARS-CoV-2 affect the brain, including direct brain invasion, neuroinflammation, and microvascular injury, we examined (1) the expression changes of AD markers in COVID-19 patients, (2) the expression of SARS-CoV-2 host factors in AD patients and healthy individuals at tissues, brain regions, and single-cell/nucleus levels. These transcriptomic analyses were accompanied by network analysis to uncover the potential mechanisms (key genes or pathways) involved in protein-protein interactions. We also compared the susceptibility of SARS-CoV-2 infection among AD patients with different APOE genotypes using the single-nucleus transcriptomic datasets