COVID-19疫情在自爆发起的三年间造成近7亿多人感染，约7百万人死亡，对全球经济发展和人类生命健康带来了巨大的打击。过往研究发现，大量的COVID-19患者和康复期患者出现了一系列神经系统症状和后遗症，如头痛、头晕、脑雾、记忆减退、认知障碍、味觉和嗅觉消失、谵妄、癫痫、运动障碍等。这些人患有阿尔茨海默症（Alzheimer’s disease, AD） 和帕金森病（Parkinson’s disease, PD） 等神经退行性疾病的风险显著增加。本研究旨在通过生物信息学分析手段研究COVID-19、AD和PD之间潜在的共同致病机制，探索COVID-19患者或康复期患者出现神经系统症状的可能分子变化，为早期干预、阻止疾病进展提供线索和帮助。在本研究中，我们采用额叶皮层的转录组数据集来检测COVID-19、AD和PD的共同差异表达基因（differentially expressed genes, DEGs）；利用功能注释、通路富集、蛋白质-蛋白质相互作用网络（protein-protein interaction, PPI）构建、hub基因鉴定、候选药物筛选和调控网络分析等方法对识别的DEGs做进一步探讨。通过上述分析过程，我们最后识别了52个DEGs、1个关键功能模块、5个hub基因、5个候选药物和10个转录因子（transcription factors, TFs）。此外，我们发现突触囊泡循环障碍和突触及突触组成相关蛋白下调是这三种疾病共有的通路改变，这表明COVID-19感染者的额叶皮质可能出现了突触异常和突触功能障碍，这种改变可能引发了神经退行性疾病的发生和进展。总之，我们的研究结果为后续探索COVID-19与神经退行性疾病之间的关联提供了新的见解和线索。我们发现的hub基因和潜在治疗靶点及药物可能提供有效的治疗策略，为防止COVID-19患者或康复期患者发展成这些严重的神经退行性疾病提供参考。

The COVID-19 pandemic has caused nearly seven million of deaths and remains a major public health burden worldwide. Previous studies found that a large number of COVID-19 patients and survivors developed neurological symptoms and might be at high risk of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). We aimed to explore the shared pathways between COVID-19, AD, and PD by using bioinformatic analysis to reveal potential mechanisms, which may explain the neurological symptoms and degeneration of brain that occur in COVID-19 patients, and to provide early intervention. In this study, gene expression datasets of the frontal cortex were employed to detect common differentially expressed genes (DEGs) of COVID-19, AD, and PD. A total of 52 common DEGs were then examined using functional annotation, protein-protein interaction (PPI) construction, candidate drug identification, and regulatory network analysis. We found that the involvement of the synaptic vesicle cycle and down-regulation of synapses and synaptic components were shared by these three diseases, suggesting that synaptic dysfunction might contribute to the onset and progress of neurodegenerative diseases caused by COVID-19. Five hub genes and one key module were obtained from the PPI network. Moreover, 5 drugs and 10 transcription factors (TFs) were also identified on the datasets. In conclusion, the results of our study provide new insights and clues for follow-up studies of the relationship between COVID-19 and neurodegenerative diseases. The hub genes and potential drugs we identified may provide promising treatment strategies to prevent COVID-19 patients from developing these disorders.