Demonstration of the impact of COVID-19 on metabolic associated fatty liver disease by bioinformatics and system biology approach

Abstract

Background: Severe coronavirus disease 2019 (COVID-19) has caused a great threat to human health. Metabolic associated fatty liver disease (MAFLD) is a liver disease with a high prevalence rate. Previous studies indicated that MAFLD led to increased mortality and severe case rates of COVID-19 patients, but its mechanism remains unclear. Methods: This study analyzed the transcriptional profiles of COVID-19 and MAFLD patients and their respective healthy controls from the perspectives of bioinformatics and systems biology to explore the underlying molecular mechanisms between the 2 diseases. Specifically, gene expression profiles of COVID-19 and MAFLD patients were acquired from the gene expression omnibus datasets and screened shared differentially expressed genes (DEGs). Gene ontology and pathway function enrichment analysis were performed for common DEGs to reveal the regulatory relationship between the 2 diseases. Besides, the hub genes were extracted by constructing a protein-protein interaction network of shared DEGs. Based on these hub genes, we conducted regulatory network analysis of microRNA/transcription factors–genes and gene - disease relationship and predicted potential drugs for the treatment of COVID-19 and MAFLD. Results: A total of 3734 and 589 DEGs were screened from the transcriptome data of MAFLD (GSE183229) and COVID-19 (GSE196822), respectively, and 80 common DEGs were identified between COVID-19 and MAFLD. Functional enrichment analysis revealed that the shared DEGs were involved in inflammatory reaction, immune response and metabolic regulation. In addition, 10 hub genes including SERPINE1, IL1RN, THBS1, TNFAIP6, GADD45B, TNFRSF12A, PLA2G7, PTGES, PTX3 and GADD45G were identified. From the interaction network analysis, 41 transcription factors and 151 micro-RNAs were found to be the regulatory signals. Some mental, Inflammatory, liver diseases were found to be most related with the hub genes. Importantly, parthenolide, luteolin, apigenin and MS-275 have shown possibility as therapeutic agents against COVID-19 and MAFLD. Conclusion: This study reveals the potential common pathogenesis between MAFLD and COVID-19, providing novel clues for future research and treatment of MAFLD and severe acute respiratory syndrome coronavirus 2 infection.

Understanding the SARS-CoV-2–Human Liver Interactome Using a Comprehensive Analysis of the Individual Virus–Host Interactions

“…It also collects all the experimentally proven data on the interactions between the 31 SARS-CoV-2 proteins and the human proteome. The quantitative SAINT analysis [36] was used to identify SARS-CoV-2 viral-host proximity interactions in human or model system cells [11,[13][14][15][16][17][18][19][20][21][22] and those with a Bayesian FDR =< 0.01 were high confidence. Scores are the sum of peptide counts from four mass spec runs with a higher score indicating a higher degree of connectivity between proteins.…”

“…As mentioned in the Introduction, we carefully selected 11 projects [11,[13][14][15][16][17][18][19][20][21][22] out of the 18 projects identified in the scientific literature between 2021 and 2023. These papers deal with characterizing hepatic metabolic processes that are viral targets in patients affected by COVID-19.…”

“…Many studies on PubMed [11,[13][14][15][16][17][18][19][20][21][22] from 2021 to 2023 reported hub genes linked to COVID-19. They aim to determine regulatory processes from datasets based on microarray or transcriptome sequencing technology.…”

Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma

“…Patients with severe COVID-19 seem to have higher rates of liver dysfunction [ 6 ]. Patients with liver dysfunction are identified to have high risk of developing severe COVID-19 [ 7 , 8 ]. Clinical data also demonstrate that patients with comorbidities fare worse than those without them [ 9 , 10 ].…”

Exploration of the link between COVID-19 and gastric cancer from the perspective of bioinformatics and systems biology

“…SARS-CoV-2 infection alters alveolar vascular permeability, which in turn leads to lung injury such as pulmonary edema, DIC, and pulmonary ischemia [14]. Not only that, SARS-CoV-2 can also spread to the brain, heart, gastrointestinal tract and other important organs through blood, which may cause adverse effects such as cerebral hemorrhage, coma, paralysis and eventually death [15][16][17][18][19]. Due to the genetic diversity and frequent genome reorganization of SARS-CoV-2, COVID-19 is likely to evolve and become seasonal epidemics [20].…”