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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease (COVID-19), has been devastated by COVID-19 in an increasing number of countries and health care systems around the world since its announcement of a global pandemic on 11 March 2020. During the pandemic, emerging novel viral mutant variants have caused multiple outbreaks of COVID-19 around the world and are prone to genetic evolution, causing serious damage to human health. As confirmed cases of COVID-19 spread rapidly, there is evidence that SARS-CoV-2 infection involves the central nervous system (CNS) and peripheral nervous system (PNS), directly or indirectly damaging neurons and further leading to neurodegenerative diseases (ND), but the molecular mechanisms of ND and CVOID-19 are unknown. We employed transcriptomic profiling to detect several major diseases of ND: Alzheimer 's disease (AD), Parkinson' s disease (PD), and multiple sclerosis (MS) common pathways and molecular biomarkers in association with COVID-19, helping to understand the link between ND and COVID-19. There were 14, 30 and 19 differentially expressed genes (DEGs) between COVID-19 and Alzheimer 's disease (AD), Parkinson' s disease (PD) and multiple sclerosis (MS), respectively; enrichment analysis showed that MAPK, IL-17, PI3K-Akt and other signaling pathways were significantly expressed; the hub genes (HGs) of DEGs between ND and COVID-19 were CRH, SST, TAC1, SLC32A1, GAD2, GAD1, VIP and SYP. Analysis of transcriptome data suggests multiple co-morbid mechanisms between COVID-19 and AD, PD, and MS, providing new ideas and therapeutic strategies for clinical prevention and treatment of COVID-19 and ND.