Table 3 Pathogenic mechanisms in COVID-19 phenotype: SARS-CoV-2—host interactions in the lung. (A), DEG and DEP analysis in other organs and tissues (B) Hub genes and pathway of innate immune response (C), Comorbidities COVID19 associated not sharing COVID19 pathogenesis (D), Comorbidities associated and related to COVID-19 pathway (E)
From: Multi-omics approach to COVID-19: a domain-based literature review
A.SARS-CoV-2—host interactions in the lung | ||
|---|---|---|
Phenotypes | Pathways | Reactome code |
Severe | Interferon type I signalling pathways ISGs and ACE2: gene highly expressed TMPRSS2 [TE107] | R-HSA-909733 |
Metabolism of proteins Significant increase of antigens processing [TE108] | R-HSA-392499 | |
Cytokine Signalling in Immune system Upregulation of proinflammatory cytokine and chemokine genes [TE116] | R-HSA-128021 | |
Neutrophil degranulation Genes involved in neutrophil extracellular traps generation (NETs) [TE117] | R-HSA-6798695 | |
Disorders of transmembrane transporters Expression of the Lipopolysaccharide (LPS) sensors [TE114] | R-HSA-5619115 | |
Mild/asymptomatic | Cytokine Signalling in Immune system Increasing of CCL2 chemokine [TE88] | R-HSA-1280215 |
Other infections | Interferon type I signalling pathways Increasing of five cytokines (IFNG, IL6, CXCL8, CXCL10 and CCL2) in in mild and severe COVID-19 patients than influenza [TE96] | R-HSA-909733 |
B. DEG and DEP analysis in other organs and tissues | ||
|---|---|---|
Phenotypes | Pathways | Reactome code |
Severe | TMPRSS2 Mediated SARS-CoV-1 Spike Protein Cleavage and Endocytosis; ACE2 overexpression [TE121] | R-HSA-2022344 |
Attachment and Entry Altered expression of ACE2 in intestinal tissue, as effect of SARS-CoV-2 ACE2 exhibits the highest co-expression correlation with TMPRSS2, SLC6A20C [TE121, TE123] | R-HSA-9678110 | |
Transport of small molecules Decrease of brain-enhanced proteins that regulate neurotransmitter synthesis (GLS, OGDH, DLD, etc.), neurotransmitter transport (GLUL, GLUD2, GLUD1), neurotransmitter receptors (HTRA3) [TE96] | R-HSA-382551 | |
Mild/asymptomatic | Diseases of haemostasis Upregulated serum proteins, such as S100A8, S100A9, serum amyloid A1 (SAA1) [TE94] | R-HSA-9671793 |
C. Hub genes and pathways of innate immune response | ||
|---|---|---|
Phenotypes | Pathways | Reactome code |
Severe | ISG15 antiviral mechanism IFN deficiency in the blood [TE130, TE89] | R-HSA-1169408 |
Cytokine Signalling in Immune system Robust levels of chemokines, including CCL2, CCL8, and CCL11. Significant increase in circulating IL6, IL1RA levels along with CXCL9 and CXCL16, CCL8 and CCL2 [TE87] | R-HSA-1280215 | |
Clathrin-mediated endocytosis Clathrin-mediated endocytosis signalling, actin cytoskeleton signalling, mechanisms of viral exit from host cells [TE136] | R-HSA-8856828 | |
Toll-like Receptor Cascades Significantly upregulated NETs [TE137] | R-HSA-168898 | |
Mild/asymptomatic | Interferon-α/β signaling Early, transient type I IFN production in the lung, that induces ISGs in the peripheral blood [TE89] | R-HSA-909733 |
Programmed Cell Death T cell apoptosis [TE111] | R-HSA-5357801 | |
D. Comorbidities COVID19 associated not sharing COVID19 pathogenesis | ||
|---|---|---|
Phenotypes | Pathways | Reactome code |
Severe | Histone Modifications (Post-translational protein modification) Several genes related to histone modifications (HAT1, HDAC2, KDM5B) were identified in severe COVID19 patients with comorbidities. [TE119] | R-HSA-597592 |
TMPRSS2 Mediated SARS-CoV-1 Spike Protein Cleavage and Endocytosis Several genes positively associated with ACE2 are regulated by KDM5B, and by specific histone acetylation. [TE119] | R-HSA-2022344 | |
E. Comorbidities associated and related to COVID-19 pathway | ||
|---|---|---|
Phenotype | Pathways | Reactome code |
Severe | Attachment and Entry Increased circulating furin levels that could cleave the spike protein and increase SARS-CoV-2 infectivity [TE121] | R-HSA-9678110 |
Glycerophospholipid biosynthesis Lipids quantified in the negative mode (arachidonic acid, oleic acid, glycerophosphoethanolamines, and glycerophosphoethanolamines); Two significant pathways: fat digestion and adsorption and glycerophospholipid metabolism. [TE145] | R-HSA-1483206 | |
Mild/asymptomatic | Glycerophospholipid biosynthesis Non-critical patients are characterized by strong alteration of lipids, including acylcarnitines [TE90] | R-HSA-1483206 |
Tryptophan catabolism Metabolic alteration in mild/asymptomatic COVID19 patients include: altered tryptophan metabolism into the kynurenine pathway, regulating inflammation and immunity [TE146] | R-HSA-71240 | |
Bacterial infection Lipid rafts are associated with SARS-CoV-2 virulence [TE143] | R-HSA-9664407 | |