Bioinformatics and system biology approach to identify the influences among COVID-19, ARDS and sepsis

Front Immunol. 2023 May 16:14:1152186. doi: 10.3389/fimmu.2023.1152186. eCollection 2023.

Abstract

Background Severe coronavirus disease 2019 (COVID -19) has led to severe pneumonia or acute respiratory distress syndrome (ARDS) worldwide. we have noted that many critically ill patients with COVID-19 present with typical sepsis-related clinical manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. The molecular mechanisms that underlie COVID-19, ARDS and sepsis are not well understood. The objectives of this study were to analyze potential molecular mechanisms and identify potential drugs for the treatment of COVID-19, ARDS and sepsis using bioinformatics and a systems biology approach. Methods Three RNA-seq datasets (GSE171110, GSE76293 and GSE137342) from Gene Expression Omnibus (GEO) were employed to detect mutual differentially expressed genes (DEGs) for the patients with the COVID-19, ARDS and sepsis for functional enrichment, pathway analysis, and candidate drugs analysis. Results We obtained 110 common DEGs among COVID-19, ARDS and sepsis. ARG1, FCGR1A, MPO, and TLR5 are the most influential hub genes. The infection and immune-related pathways and functions are the main pathways and molecular functions of these three diseases. FOXC1, YY1, GATA2, FOXL, STAT1 and STAT3 are important TFs for COVID-19. mir-335-5p, miR-335-5p and hsa-mir-26a-5p were associated with COVID-19. Finally, the hub genes retrieved from the DSigDB database indicate multiple drug molecules and drug-targets interaction. Conclusion We performed a functional analysis under ontology terms and pathway analysis and found some common associations among COVID-19, ARDS and sepsis. Transcription factors-genes interaction, protein-drug interactions, and DEGs-miRNAs coregulatory network with common DEGs were also identified on the datasets. We believe that the candidate drugs obtained in this study may contribute to the effective treatment of COVID-19.

Keywords: ARDS; COVID-19; differentially expressed genes; drug molecule; gene ontology; protein-protein interaction; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / genetics
  • Computational Biology / methods
  • Gene Expression Profiling / methods
  • Humans
  • MicroRNAs* / genetics
  • Respiratory Distress Syndrome* / drug therapy
  • Respiratory Distress Syndrome* / genetics
  • Sepsis* / complications
  • Sepsis* / drug therapy
  • Sepsis* / genetics

Substances

  • MicroRNAs

Grants and funding

This work was supported by the Natural Science Foundation of Hunan Province (No. 2022JJ40006) and the scientific research project of The First People’s Hospital of Chenzhou (No. N2021-14). This work was also supported by the scientific research project of The First People’s Hospital of Chenzhou (No.CZYY202207), the key research and development project of chenzhou (No.2020013), the Technology Research and Development Center of chenzhou(2021) and the Science and Technology Key Development Project of Chenzhou City (No. ZDYF2020012).