KEGG   DISEASE: COVID-19
Entry
H02398                      Disease                                

Name
COVID-19;
Coronavirus disease 2019
Description
Coronavirus disease of 2019 (COVID-19) is a highly contagious respiratory infection that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infects alveolar epithelial cells [mainly alveolar epithelial type 2 (AEC2) cells] through the angiotensin-converting enzyme 2 (ACE2) receptor. Upon the occupancy of ACE2 by SARS-CoV-2, the increased serum level of free Angiotensin II (Ang II) due to a reduction of ACE2-mediated degradation promotes activation of the NF-kappa B pathway via Ang II type 1 receptor (AT1R), followed by  interleukin-6 (IL-6) production. SARS-CoV-2 also activates the innate immune system; macrophage stimulation triggers the overproduction of pro-inflammatory cytokines, including IL-6, and the "cytokine storm", which results in systemic inflammatory response syndrome and multiple organ failure. The combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined to drive the severe features of COVID-19.
Category
Infectious disease
Brite
Infectious diseases [BR:br08401]
 Viral infections
  Infections caused by +ssRNA viruses
   H02398  COVID-19
Pathway
hsa05171  Coronavirus disease - COVID-19
Network
nt06122  IFN signaling (viruses)
nt06133  RLR signaling (viruses)
nt06136  Complement activation (viruses)
nt06141  Translation (viruses)
nt06171  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
  Element
N01307  SARS-CoV-2 S to AngII-AT1R-NOX2 signaling pathway
N01309  SARS-CoV-2 nsp3 to MDA5-IRF7/3 signaling pathway
N01310  SARS-CoV-2 nsp13 to RIG-I-IRF7/3 signaling pathway
N01312  SARS-CoV-2 S to lectin pathway of complement activation
N01314  SARS-CoV-2 S to classical pathway of complement activation
N01316  SARS-CoV-2 S/N to lectin pathway of coagulation activation
N01318  SARS-CoV-2 nsp1 to translation initiation
N01319  SARS-CoV-2 nsp6 and ORF6 to RIG-I-IRF7/3 signaling pathway
N01320  SARS-CoV-2 nsp3 to RIG-I-IRF7/3 signaling pathway
N01321  SARS-CoV-2 nsp1/6/13, ORF3a/6/7b and M to IFN signaling pathway
N01322  SARS-CoV-2 nsp6/13 and ORF7a/7b to IFN signaling pathway
Pathogen
SARS-CoV-2 [GN:T40361]
Drug
Remdesivir [DR:D11472]
COVID-19 mRNA vaccine [DR:D12114]
Reference
  Authors
Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian JH, Pei YY, Yuan ML, Zhang YL, Dai FH, Liu Y, Wang QM, Zheng JJ, Xu L, Holmes EC, Zhang YZ
  Title
A new coronavirus associated with human respiratory disease in China.
  Journal
Nature 10.1038/s41586-020-2008-3 (2020)
DOI:10.1038/s41586-020-2008-3
Reference
  Authors
Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, Ippolito G, Mchugh TD, Memish ZA, Drosten C, Zumla A, Petersen E
  Title
The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China.
  Journal
Int J Infect Dis 91:264-266 (2020)
DOI:10.1016/j.ijid.2020.01.009
Reference
  Authors
Kiselevskiy M, Shubina I, Chikileva I, Sitdikova S, Samoylenko I, Anisimova N, Kirgizov K, Suleimanova A, Gorbunova T, Varfolomeeva S
  Title
Immune Pathogenesis of COVID-19 Intoxication: Storm or Silence?
  Journal
Pharmaceuticals (Basel) 13:E166 (2020)
DOI:10.3390/ph13080166
Reference
  Authors
Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, Hirano T
  Title
How COVID-19 induces cytokine storm with high mortality.
  Journal
Inflamm Regen 40:37 (2020)
DOI:10.1186/s41232-020-00146-3
Reference
  Authors
Zhang C, Wu Z, Li JW, Zhao H, Wang GQ
  Title
Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality.
  Journal
Int J Antimicrob Agents 55:105954 (2020)
DOI:10.1016/j.ijantimicag.2020.105954
Reference
  Authors
Lo MW, Kemper C, Woodruff TM
  Title
COVID-19: Complement, Coagulation, and Collateral Damage.
  Journal
J Immunol 205:1488-1495 (2020)
DOI:10.4049/jimmunol.2000644
Reference
  Authors
Noris M, Benigni A, Remuzzi G
  Title
The case of complement activation in COVID-19 multiorgan impact.
  Journal
Kidney Int 98:314-322 (2020)
DOI:10.1016/j.kint.2020.05.013
Reference
  Authors
Java A, Apicelli AJ, Liszewski MK, Coler-Reilly A, Atkinson JP, Kim AH, Kulkarni HS
  Title
The complement system in COVID-19: friend and foe?
  Journal
JCI Insight 5:140711 (2020)
DOI:10.1172/jci.insight.140711
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