Entry Name Coronavirus disease - COVID-19
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.
Class Human Diseases; Infectious disease: viralBRITE hierarchy
Pathway map Ortholog table Disease Reference Authors Harrison AG, Lin T, Wang P
Title Mechanisms of SARS-CoV-2 Transmission and Pathogenesis.
Journal Reference Authors Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G
Title Immunity, endothelial injury and complement-induced coagulopathy in COVID-19.
Journal Reference Authors Battagello DS, Dragunas G, Klein MO, Ayub ALP, Velloso FJ, Correa RG
Title Unpuzzling COVID-19: tissue-related signaling pathways associated with SARS-CoV-2 infection and transmission.
Journal Reference Authors Felsenstein S, Herbert JA, McNamara PS, Hedrich CM
Title COVID-19: Immunology and treatment options.
Journal 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 Reference Authors Mahmudpour M, Roozbeh J, Keshavarz M, Farrokhi S, Nabipour I
Title COVID-19 cytokine storm: The anger of inflammation.
Journal Reference Authors Farooqi F, Dhawan N, Morgan R, Dinh J, Nedd K, Yatzkan G
Title Treatment of Severe COVID-19 with Tocilizumab Mitigates Cytokine Storm and Averts Mechanical Ventilation During Acute Respiratory Distress: A Case Report and Literature Review.
Journal Reference Authors Jamilloux Y, Henry T, Belot A, Viel S, Fauter M, El Jammal T, Walzer T, Francois B, Seve P
Title Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions.
Journal 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 Reference Authors Curran CS, Rivera DR, Kopp JB
Title COVID-19 Usurps Host Regulatory Networks.
Journal Reference Authors Quan C, Li C, Ma H, Li Y, Zhang H
Title Immunopathogenesis of Coronavirus-Induced Acute Respiratory Distress Syndrome (ARDS): Potential Infection-Associated Hemophagocytic Lymphohistiocytosis.
Journal Reference Authors Ahmed-Hassan H, Sisson B, Shukla RK, Wijewantha Y, Funderburg NT, Li Z, Hayes D Jr, Demberg T, Liyanage NPM
Title Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections.
Journal Reference Authors Tay MZ, Poh CM, Renia L, MacAry PA, Ng LFP
Title The trinity of COVID-19: immunity, inflammation and intervention.
Journal Reference Authors Xia H, Cao Z, Xie X, Zhang X, Chen JY, Wang H, Menachery VD, Rajsbaum R, Shi PY
Title Evasion of Type I Interferon by SARS-CoV-2.
Journal Reference Authors Hartenian E, Nandakumar D, Lari A, Ly M, Tucker JM, Glaunsinger BA
Title The molecular virology of coronaviruses.
Journal Reference Authors Amor S, Fernandez Blanco L, Baker D
Title Innate immunity during SARS-CoV-2: evasion strategies and activation trigger hypoxia and vascular damage.
Journal Reference Authors Catanzaro M, Fagiani F, Racchi M, Corsini E, Govoni S, Lanni C
Title Immune response in COVID-19: addressing a pharmacological challenge by targeting pathways triggered by SARS-CoV-2.
Journal Reference Authors Jafarzadeh A, Chauhan P, Saha B, Jafarzadeh S, Nemati M
Title Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions.
Journal Reference Authors Merad M, Martin JC
Title Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages.
Journal Reference Authors South AM, Tomlinson L, Edmonston D, Hiremath S, Sparks MA
Title Controversies of renin-angiotensin system inhibition during the COVID-19 pandemic.
Journal Reference Authors Furuhashi M, Moniwa N, Takizawa H, Ura N, Shimamoto K
Title Potential differential effects of renin-angiotensin system inhibitors on SARS-CoV-2 infection and lung injury in COVID-19.
Journal Reference Authors Gemmati D, Bramanti B, Serino ML, Secchiero P, Zauli G, Tisato V
Title COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?
Journal Reference Authors Kielian M
Title Enhancing host cell infection by SARS-CoV-2.
Journal Reference Authors Risitano AM, Mastellos DC, Huber-Lang M, Yancopoulou D, Garlanda C, Ciceri F, Lambris JD
Title Complement as a target in COVID-19?
Journal Reference Authors Noris M, Benigni A, Remuzzi G
Title The case of complement activation in COVID-19 multiorgan impact.
Journal Reference Authors Polycarpou A, Howard M, Farrar CA, Greenlaw R, Fanelli G, Wallis R, Klavinskis LS, Sacks S
Title Rationale for targeting complement in COVID-19.
Journal Reference Authors Teuwen LA, Geldhof V, Pasut A, Carmeliet P
Title COVID-19: the vasculature unleashed.
Journal Reference Authors Jodele S, Kohl J
Title Tackling COVID-19 infection through complement-targeted immunotherapy.
Journal Reference Authors Chauhan AJ, Wiffen LJ, Brown TP
Title COVID-19: A collision of complement, coagulation and inflammatory pathways.
Journal Reference Authors Colling ME, Kanthi Y
Title COVID-19-associated coagulopathy: An exploration of mechanisms.
Journal Reference Authors McFadyen JD, Stevens H, Peter K
Title The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications.
Journal Reference Authors Shi M, Wang L, Fontana P, Vora S, Zhang Y, Fu TM, Lieberman J, Wu H
Title SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism.
Journal Reference Authors Paniri A, Akhavan-Niaki H
Title Emerging role of IL-6 and NLRP3 inflammasome as potential therapeutic targets to combat COVID-19: Role of lncRNAs in cytokine storm modulation.
Journal Reference Authors Omarjee L, Janin A, Perrot F, Laviolle B, Meilhac O, Mahe G
Title Targeting T-cell senescence and cytokine storm with rapamycin to prevent severe progression in COVID-19.
Journal Reference Authors Zhang S, Li L, Shen A, Chen Y, Qi Z
Title Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia.
Journal Related map04270 Vascular smooth muscle contraction
map04610 Complement and coagulation cascades
map04613 Neutrophil extracellular trap formation
map04620 Toll-like receptor signaling pathway
map04621 NOD-like receptor signaling pathway
map04622 RIG-I-like receptor signaling pathway
map04650 Natural killer cell mediated cytotoxicity
map04666 Fc gamma R-mediated phagocytosis
map04670 Leukocyte transendothelial migration
KO pathway LinkDB All DBs
