Discovering common pathogenetic processes between COVID-19 and sepsis by bioinformatics and system biology approach

Abstract

Corona Virus Disease 2019 (COVID-19), an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread rapidly worldwide, resulting in a pandemic with a high mortality rate. In clinical practice, we have noted that many critically ill or critically ill patients with COVID-19 present with typical sepsis-related clinical manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. In addition, it has been demonstrated that severe COVID-19 has some pathological similarities with sepsis, such as cytokine storm, hypercoagulable state after blood balance is disrupted and neutrophil dysfunction. Considering the parallels between COVID-19 and non-SARS-CoV-2 induced sepsis (hereafter referred to as sepsis), the aim of this study was to analyze the underlying molecular mechanisms between these two diseases by bioinformatics and a systems biology approach, providing new insights into the pathogenesis of COVID-19 and the development of new treatments. Specifically, the gene expression profiles of COVID-19 and sepsis patients were obtained from the Gene Expression Omnibus (GEO) database and compared to extract common differentially expressed genes (DEGs). Subsequently, common DEGs were used to investigate the genetic links between COVID-19 and sepsis. Based on enrichment analysis of common DEGs, many pathways closely related to inflammatory response were observed, such as Cytokine-cytokine receptor interaction pathway and NF-kappa B signaling pathway. In addition, protein-protein interaction networks and gene regulatory networks of common DEGs were constructed, and the analysis results showed that ITGAM may be a potential key biomarker base on regulatory analysis. Furthermore, a disease diagnostic model and risk prediction nomogram for COVID-19 were constructed using machine learning methods. Finally, potential therapeutic agents, including progesterone and emetine, were screened through drug-protein interaction networks and molecular docking simulations. We hope to provide new strategies for future research and treatment related to COVID-19 by elucidating the pathogenesis and genetic mechanisms between COVID-19 and sepsis.

Exploration of the Link Between COVID-19 and Alcoholic Hepatitis from the Perspective of Bioinformatics and Systems Biology

“…The results showed that TFs (FOXC1, YY1, GATA2, SREBF1 and FOXL1) were associated with CXCR4, CXCL1, COL6A3, COL1A2 and ITGA6 and miRNAs (hsa-mir-1-3p, hsa-mir-26b-5p, hsa-mir-29b-3p, hsa-mir-105-5P and hsa-mir-4781-5P) were closely regulated with THBS2, SOX9, THY1, COL1A2 and TIMP. In previous bioinformatics analyses, Ahmed, Islam, and Lu Lu et al found FOXC1, YY1, GATA2, and FOXL1 are significant TFs for COVID-19 (6,49,50). Pharmacological studies have also found that SREBF1, as a key regulator of lipid-metabolizing enzymes connected closely with the procession of AH, is the transcription factor most activated by several effective antiviral drugs in vitro and may become A pivot therapeutic spot for both AH and COVID-19 (51,52).…”

“…Neutrophils, as "professional" phagocytes, possess a large number of antibacterial "weapons" in their granules, allowing them to destroy pathogens during phagocytosis. During the degranulation process, bactericidal enzymes can also be released from the cell (37).The mechanism of this process leading to SARS-CoV-2 exists in the process of neutrophil extracellular traps (NETs) modified by bactericidal proteins in granules and cytoplasm, which indicates that we can disrupt the vicious cycle of hepatocellular inflammation in patients with new coronary pneumonia by activating neutrophils and promoting the formation of NETs (6).…”

“…At the equal time, enhancing the expression of ACE2, which is one of the viral host receptors, can block the entry of the virus and protect against infection through the novel coronavirus and potentially different coronaviruses (5). Severe COVID-19 frequently presents pathologically with pulmonary and extra-pulmonary organ dysfunction (6). Previous research suggested that the lungs are the organs most affected by the way of the novel coronavirus accompanied with a massive quantity of immune cell activation and the release of inflammatory factor (7,8).…”

Exploration of the link between COVID‐19 and alcoholic hepatitis from the perspective of bioinformatics and systems biology

“…The results showed that TFs (FOXC1, YY1, GATA2, SREBF1, and FOXL1) were associated with CXCR4, CXCL1, COL6A3, COL1A2, and ITGA6 and miRNAs (hsa‐mir‐1‐3p, hsa‐mir‐26b‐5p, hsa‐mir‐29b‐3p, hsa‐mir‐105‐5P, and hsa‐mir‐4781‐5P) were closely regulated with THBS2, SOX9, THY1, COL1A2, and TIMP. In previous bioinformatics analyses, Ahmed, Islam, and Lu Lu et al found FOXC1, YY1, GATA2, and FOXL1 are significant TFs for COVID‐19 37,50,51 . Pharmacological studies have also found that SREBF1, as a key regulator of lipid‐metabolizing enzymes connected closely with the procession of AH, is the transcription factor most activated by several effective antiviral drugs in vitro and may become A pivot therapeutic spot for both AH and COVID‐19 52,53 .…”

“…5 Severe COVID-19 frequently presents pathologically with pulmonary and extra-pulmonary organ dysfunction. 6 Previous research suggested that the lungs are the organs most affected by the way of the novel coronavirus accompanied with a massive quantity of immune cell activation and the release of inflammatory factor. 7,8 Extrapulmonary organs, on the other hand, have varying levels of tissue injury and inflammatory response, demonstrated as multiorgan dysfunction and systematic inflammatory reaction.…”