In this study, through bioinformatics analysis of the public databases, we studied the changes in gene expression in COVID-19 and ALF epithelial cells under acute injury and identified hub genes such as CDC20, CENPF, KIF4, KIF11, NUSAP1, TPX2, and PTTG1. The hub genes and their enrichment pathways helped to clarify the mechanisms of impairment in ALF and COVID-19. This evidence concerns the gene CDC20 and COVID-19.