Post-COVID neuroinflammation (Homo sapiens)

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Indirect route12, 17 Direct route12Suprachiasmatic nucleus of the hypothalamusSARS-CoV-2neutrophilHematological route15, 17Humoral route12macrophageSTEP 3 (cytokine production):Actual peripheral cytokine releaseinduced by STEP 2 molecules released by immune cells1Trigeminal nerve4STEP 1 (recognition):PRRs on innate immune cells recognize PAMPs and DAMPS of SARS-CoV-21, 15monocyteVagus nerve4, 13, 17, 21Trojan/indirectOcular nerve3, 7, 13Non-Trojan/directOlfactory nerve13, 14, 17, 23STEP 2 (activation + signal transduction):Activation of signaling molecules 1NK cellNeuronal route12BBBPotential STEP 4 (cytokine storm):The immune response may be too strong, resulting in excess cytokine production and release, resulting in a cytokine storm 12Neuronal routeGlossopharyngeal nerve10, 21(DAMPs)Damage-associated molecular patterns Retinohypothalamic tractOlfactory bulb (CNS)Medulla oblongata of the brainstemNF-κB inhibitorMAPK pathwaysubstance P(3+)INF2ATLR3IL18MAPK1111519151IL8TLR4IL422IFNG9, 20IL26HMGB15IL1013, 15TLR815TNF1, 2, 13p38 MAPK15IL6GFAP15E proteinIL12A20TLR716CCL1115ssRNAFURIN9ACE29TMPRSS29disrupted BBBvirus enters CNSHMGB15NK cellIL1B1, 13, 18IL61, 2, 6, 13, 18IL1A1CXCL85, 16p38 MAPK15BBB intactvirus enters CNSin immune cellPeriphirally released pro-inflammatory cytokinesE protein1ssRNA8TLR4substance P(3+)1419


Description

Post-COVID is the sequela disease of COVID-19, a SARS-CoV-2 infectious disease that is characterized by long-term persistent symptoms. To understand the underlying disease mechanisms of post-COVID and the role of persistent neuroinflammation herein, this pathway visualizes the direct and indirect route of SARS-CoV-2-mediated neuroinflammation, which may induce dysautonomia, a major post-COVID symptom. The direct and indirect route are subdivided in a neurological and hematological, and a neurological and humoral route, respectively.

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Bibliography

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  1. Wei ZD, Liang K, Shetty AK; ''Complications of COVID-19 on the Central Nervous System: Mechanisms and Potential Treatment for Easing Long COVID.''; Aging Dis, 2023 PubMed Europe PMC Scholia
  2. Proal AD, VanElzakker MB; ''Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms.''; Front Microbiol, 2021 PubMed Europe PMC Scholia
  3. Leng A, Shah M, Ahmad SA, Premraj L, Wildi K, Li Bassi G, Pardo CA, Choi A, Cho SM; ''Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics.''; Cells, 2023 PubMed Europe PMC Scholia
  4. Nassar A, Ibrahim IM, Amin FG, Magdy M, Elgharib AM, Azzam EB, Nasser F, Yousry K, Shamkh IM, Mahdy SM, Elfiky AA; ''A Review of Human Coronaviruses' Receptors: The Host-Cell Targets for the Crown Bearing Viruses.''; Molecules, 2021 PubMed Europe PMC Scholia
  5. Liu J, Han X, Zhang T, Tian K, Li Z, Luo F; ''Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy.''; J Hematol Oncol, 2023 PubMed Europe PMC Scholia
  6. Jammoul M, Naddour J, Madi A, Reslan MA, Hatoum F, Zeineddine J, Abou-Kheir W, Lawand N; ''Investigating the possible mechanisms of autonomic dysfunction post-COVID-19.''; Auton Neurosci, 2023 PubMed Europe PMC Scholia
  7. Zhou L, Xu Z, Guerra J, Rosenberg AZ, Fenaroli P, Eberhart CG, Duh EJ; ''Expression of the SARS-CoV-2 Receptor ACE2 in Human Retina and Diabetes-Implications for Retinopathy.''; Invest Ophthalmol Vis Sci, 2021 PubMed Europe PMC Scholia
  8. Tziolos NR, Ioannou P, Baliou S, Kofteridis DP; ''Long COVID-19 Pathophysiology: What Do We Know So Far?''; Microorganisms, 2023 PubMed Europe PMC Scholia
  9. Paul BD, Lemle MD, Komaroff AL, Snyder SH; ''Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome.''; Proc Natl Acad Sci U S A, 2021 PubMed Europe PMC Scholia
  10. Zadeh FH, Wilson DR, Agrawal DK; ''Long COVID: Complications, Underlying Mechanisms, and Treatment Strategies.''; Arch Microbiol Immunol, 2023 PubMed Europe PMC Scholia
  11. Ylikoski J, Lehtimäki J, Pääkkönen R, Mäkitie A; ''Prevention and Treatment of Life-Threatening COVID-19 May Be Possible with Oxygen Treatment.''; Life (Basel), 2022 PubMed Europe PMC Scholia
  12. Meade E, Garvey M; ''The Role of Neuro-Immune Interaction in Chronic Pain Conditions; Functional Somatic Syndrome, Neurogenic Inflammation, and Peripheral Neuropathy.''; Int J Mol Sci, 2022 PubMed Europe PMC Scholia
  13. Zhang J; ''Investigating neurological symptoms of infectious diseases like COVID-19 leading to a deeper understanding of neurodegenerative disorders such as Parkinson's disease.''; Front Neurol, 2022 PubMed Europe PMC Scholia
  14. Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB; ''Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).''; Elife, 2023 PubMed Europe PMC Scholia
  15. Kikinis Z, Castañeyra-Perdomo A, González-Mora JL, Rushmore RJ, Toppa PH, Haggerty K, Papadimitriou G, Rathi Y, Kubicki M, Kikinis R, Heller C, Yeterian E, Besteher B, Pallanti S, Makris N; ''Investigating the structural network underlying brain-immune interactions using combined histopathology and neuroimaging: a critical review for its relevance in acute and long COVID-19.''; Front Psychiatry, 2024 PubMed Europe PMC Scholia
  16. Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB; ''Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).''; Elife, 2023 PubMed Europe PMC Scholia
  17. Negrut N, Menegas G, Kampioti S, Bourelou M, Kopanyi F, Hassan FD, Asowed A, Taleouine FZ, Ferician A, Marian P; ''The Multisystem Impact of Long COVID: A Comprehensive Review.''; Diagnostics (Basel), 2024 PubMed Europe PMC Scholia
  18. Janket SJ, Fraser DD, Baird AE, Tamimi F, Sohaei D, Conte HA, Prassas I, Diamandis EP; ''Tachykinins and the potential causal factors for post-COVID-19 condition.''; Lancet Microbe, 2023 PubMed Europe PMC Scholia
  19. Sideratou CM, Papaneophytou C; ''Persisting Shadows: Unraveling the Impact of Long COVID-19 on Respiratory, Cardiovascular, and Nervous Systems.''; Infect Dis Rep, 2023 PubMed Europe PMC Scholia
  20. Liu J, Han X, Zhang T, Tian K, Li Z, Luo F; ''Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy.''; J Hematol Oncol, 2023 PubMed Europe PMC Scholia
  21. Lv Y, Zhang T, Cai J, Huang C, Zhan S, Liu J; ''Bioinformatics and systems biology approach to identify the pathogenetic link of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.''; Front Immunol, 2022 PubMed Europe PMC Scholia
  22. Low RN, Low RJ, Akrami A; ''A review of cytokine-based pathophysiology of Long COVID symptoms.''; Front Med (Lausanne), 2023 PubMed Europe PMC Scholia
  23. Vallée A; ''Dysautonomia and Implications for Anosmia in Long COVID-19 Disease.''; J Clin Med, 2021 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
134336view13:32, 20 July 2024EweitzOntology Term : 'natural killer cell' added !
134335view13:32, 20 July 2024EweitzOntology Term : 'monocyte' added !
134334view13:32, 20 July 2024EweitzOntology Term : 'neutrophil' added !
134333view13:31, 20 July 2024EweitzOntology Term : 'macrophage' added !
134332view13:30, 20 July 2024EweitzEconomize layout
134331view13:27, 20 July 2024EweitzEconomize layout
134330view13:25, 20 July 2024EweitzRefine container label placement
134121view08:38, 22 June 2024EgonwMade two pathways clickable
134118view19:35, 21 June 2024KhanspersOntology Term : 'signaling pathway' added !
134117view19:33, 21 June 2024KhanspersOntology Term : 'COVID-19' added !
134116view19:33, 21 June 2024KhanspersModified title
134100view13:05, 16 June 2024EgonwAnd a second one which I had not spotted the first time
134099view13:04, 16 June 2024EgonwUpdated an old data source
134098view11:43, 16 June 2024Laura AdmiraalNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ACE2ProteinQ9BYF1 (Uniprot-TrEMBL)
CCL11ProteinP51671 (Uniprot-TrEMBL)
CXCL8ProteinP10145 (Uniprot-TrEMBL)
E proteinProteinP0DTC4 (Uniprot-TrEMBL)
FURINProteinP09958 (Uniprot-TrEMBL)
GFAPGeneProductP14136 (Uniprot-TrEMBL)
HMGB1ProteinP09429 (Uniprot-TrEMBL) DAMP
IFNGProteinP01579 (Uniprot-TrEMBL)
IL10ProteinP22301 (Uniprot-TrEMBL)
IL12AProteinP29459 (Uniprot-TrEMBL)
IL18ProteinQ14116 (Uniprot-TrEMBL)
IL1AProteinP01583 (Uniprot-TrEMBL)
IL1BProteinP01584 (Uniprot-TrEMBL)
IL2ProteinP60568 (Uniprot-TrEMBL)
IL4ProteinP05112 (Uniprot-TrEMBL)
IL6ProteinP05231 (Uniprot-TrEMBL)
IL8ProteinP10145 (Uniprot-TrEMBL)
INF2AProteinP01563 (Uniprot-TrEMBL)
MAPK pathwayPathwayWP382 (WikiPathways)
MAPK1ProteinP28482 (Uniprot-TrEMBL)
NF-κB inhibitorMetaboliteCHEBI:73240 (ChEBI)
TLR3ProteinO15455 (Uniprot-TrEMBL)
TLR4ProteinO00206 (Uniprot-TrEMBL)
TLR7ProteinQ9NYK1 (Uniprot-TrEMBL)
TLR8ProteinQ9NR97 (Uniprot-TrEMBL)
TMPRSS2ProteinO15393 (Uniprot-TrEMBL)
TNFProteinP01375 (Uniprot-TrEMBL)
p38 MAPKPathway
p38 MAPKPathwayWP400 (WikiPathways)
ssRNARnaNC_045512.2 (RefSeq)
substance P(3+)MetaboliteCHEBI:190692 (ChEBI)

Annotated Interactions

No annotated interactions

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