Objective: We used public data to analyze the proteomics, metabolomics and transcriptomics characteristics of COVID-19 patients to identify potential therapeutic targets. More importantly, we also collected clinical data for verification to make the analysis results more reliable. Methods: Download the serum proteomics and metabolomics data of COVID-19 patients and describe their changes in serum proteins and metabolites, and use bioinformatics analysis methods to identify potential biomarkers and therapeutic targets. Finally, clinical data and experimental data of cell infection were combined for verification. Results: It was found that the serum apolipoprotein A1 (APOA1) protein level in COVID-19 patients was down-regulated (log2FC = -0.39, false discovery rate (FDR) < 0.001), and the degree of reduction in the severe group was more significant (kruskal-test p = 2.5e-05). What is more, APOA1 was not only expressed lower in male patients (Wilcox-test p = 0.012), but also negatively correlated with C-reactive protein (CRP, r = -0.37, p = 0.019). The experiment data from SARSCoV-2 infected cells further showed that the protein and transcript level of APOA1 gradually decreased as the infection time increased, and the transcription level (log2FC = -8.3, FDR = 0.0015) was more down-regulated than protein level (log2FC = -0.95, FDR = 0.0014). More importantly, the collected clinical data also confirmed that APOA1 was down-regulated in COVID-19 patients (kruskal-test p = 0.001), and APOA1 levels are negatively correlated with IL6 (r = -0.396, p = 2.22e-07), D-dimers (DD, r = -0.262, p = 8.19e-04), prothrombin time (PT, r = -0.464, p = 6.68e10) and thrombin time (TT, r = -0.279, p = 3.46e-04). Conclusion: The degree of down-regulation of APOA1 is positively correlated with the severity of COVID-19, and the expression level of APOA1 is negatively correlated with CRP, IL6, DD, PT, TT, and positively correlated with HD and LDL. This indicates that APOA1 may be a key molecule in tandem acute inflammatory response, coagulation abnormalities and cholesterol metabolism disorder in COVID-19, and could be a potential therapeutic target.