COVID-19 adverse outcome pathway (Homo sapiens)

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22CCL3Positive regulation ofleukocyte activationToll-likereceptor signalingTNFCytokines andinflammatoryresponseIL2CSF3IL8CXCL10IL6IL7IL1BCCL2IL10IL2RALTF danger signalresponse pathwayLung fibrosisKE22KE1KE33AO (KE:1751) - Increased mortalityMIELegendMIE (KE:1739) - Binding of S protein to ACE receptorKE4 (KE:1748) - Increase, the risk of acute respiratory failureKE1 (KE:1738) - Enhanced viral entry and gene expressionKE2 (KE:1496) - Increased, secretion of proinflammatory and profibrotic mediators15 genes included in the pathway:genes with direct evidence of associationto COVID-19 in the Comparative Toxicogenomics Database( related to the adverse outcome pathway foracute respiratory distress associated mortality (AOP:320)KE3 (KE:1750) - Increase inflammatory immune responses1, 2ACE2AGTTMPRSS2SARS-CoV-2 andCOVID-19 pathwaySARS-CoV-2 and ACE2 receptor:molecular mechanisms andpotential therapeutic target


Experimental pathway to investigate overlap of Covid-19 downstream effects and adverse outcome pathways related to lung injury.

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Ontology Terms



  1. Labib S, Williams A, Yauk CL, Nikota JK, Wallin H, Vogel U, Halappanavar S; ''Nano-risk Science: application of toxicogenomics in an adverse outcome pathway framework for risk assessment of multi-walled carbon nanotubes.''; Part Fibre Toxicol, 2016 PubMed Europe PMC Scholia
  2. Nymark P, Rieswijk L, Ehrhart F, Jeliazkova N, Tsiliki G, Sarimveis H, Evelo CT, Hongisto V, Kohonen P, Willighagen E, Grafström RC; ''A Data Fusion Pipeline for Generating and Enriching Adverse Outcome Pathway Descriptions.''; Toxicol Sci, 2018 PubMed Europe PMC Scholia
  3. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S; ''A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9.''; Circ Res, 2000 PubMed Europe PMC Scholia


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120510view12:02, 10 December 2021EweitzMove groups for economical layout
120509view11:35, 10 December 2021EweitzPad containers for readability, refine layout
118878view12:05, 3 June 2021EweitzOntology Term : 'pulmonary fibrosis' added !
118830view09:11, 2 June 2021EweitzOntology Term : 'COVID-19' added !
116452view09:55, 7 May 2021EweitzModified title
111616view20:41, 29 August 2020EgonwModified title
111408view16:12, 6 August 2020EveloModified title
111156view08:39, 21 July 2020EgonwAnother pathway clickable
111112view09:12, 13 July 2020EgonwMade the pathways clickable
110309view16:07, 3 May 2020EgonwAdded missing @Type annotation
110048view08:34, 15 April 2020PennyUpdated connection between ACE2 and AGT. Added link to WP4883.
109962view08:48, 8 April 2020PennyAdded date of access for CTD
109961view08:47, 8 April 2020PennyAdded reference to origin of genes
109960view08:39, 8 April 2020PennyUpdates in line with AOP:320 and analysis of COVID-19 genes
109947view13:34, 7 April 2020FehrhartOntology Term : 'signaling pathway' added !
109944view13:23, 7 April 2020PennyNew pathway

External references


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NameTypeDatabase referenceComment
ACE2GeneProduct59272 (Entrez Gene)
AGTGeneProduct183 (Entrez Gene)
CCL2GeneProduct6347 (Entrez Gene)
CCL3GeneProduct6348 (Entrez Gene)
CSF3GeneProduct1440 (Entrez Gene)
CXCL10GeneProduct3627 (Entrez Gene)
Cytokines and


PathwayWP530 (WikiPathways)
IL10GeneProduct3586 (Entrez Gene)
IL1BGeneProduct3553 (Entrez Gene)
IL2GeneProduct3558 (Entrez Gene)
IL2RAGeneProduct3559 (Entrez Gene)
IL6GeneProduct3569 (Entrez Gene)
IL7GeneProduct3574 (Entrez Gene)
IL8GeneProduct3576 (Entrez Gene)
LTF danger signal response pathwayPathwayWP4478 (WikiPathways)
Lung fibrosisPathwayWP3624 (WikiPathways)
Positive regulation of leukocyte activationPathwayGO:0002696 (Other)
SARS-CoV-2 and COVID-19 pathwayPathwayWP4846 (WikiPathways)
SARS-CoV-2 and ACE2 receptor:

molecular mechanisms and

potential therapeutic target
PathwayWP4883 (WikiPathways)
TMPRSS2GeneProduct7113 (Entrez Gene)
TNFGeneProduct7124 (Entrez Gene)
Toll-like receptor signalingPathwayWP75 (WikiPathways)

Annotated Interactions

SourceTargetTypeDatabase referenceComment
ACE2AGTmim-modification882484 (BioGrid) Proteolytic processing
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