COVID-19;
Coronavirus disease 2019

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.

Infectious disease

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)

SARS-CoV-2 [GN:T40361]

Remdesivir [DR:D11472]
Bamlanivimab [DR:D11936]
Etesevimab [DR:D11944]
Tozinameran [DR:D11971]
Sotrovimab [DR:D12014]
Elasomeran [DR:D12114]
COVID-19 vaccine [DR:D12115]
COVID-19 vaccine [DR:D12129]

PMID:32015508

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

A new coronavirus associated with human respiratory disease in China.

Nature 10.1038/s41586-020-2008-3 (2020)
DOI:10.1038/s41586-020-2008-3

PMID:31953166

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

The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China.

Int J Infect Dis 91:264-266 (2020)
DOI:10.1016/j.ijid.2020.01.009

PMID:32722596

Kiselevskiy M, Shubina I, Chikileva I, Sitdikova S, Samoylenko I, Anisimova N, Kirgizov K, Suleimanova A, Gorbunova T, Varfolomeeva S

Immune Pathogenesis of COVID-19 Intoxication: Storm or Silence?

Pharmaceuticals (Basel) 13:E166 (2020)
DOI:10.3390/ph13080166

PMID:33014208

Hojyo S, Uchida M, Tanaka K, Hasebe R, Tanaka Y, Murakami M, Hirano T

How COVID-19 induces cytokine storm with high mortality.

Inflamm Regen 40:37 (2020)
DOI:10.1186/s41232-020-00146-3

PMID:32234467

Zhang C, Wu Z, Li JW, Zhao H, Wang GQ

Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality.

Int J Antimicrob Agents 55:105954 (2020)
DOI:10.1016/j.ijantimicag.2020.105954

PMID:32699160

Lo MW, Kemper C, Woodruff TM

COVID-19: Complement, Coagulation, and Collateral Damage.

J Immunol 205:1488-1495 (2020)
DOI:10.4049/jimmunol.2000644

PMID:32461141

Noris M, Benigni A, Remuzzi G

The case of complement activation in COVID-19 multiorgan impact.

Kidney Int 98:314-322 (2020)
DOI:10.1016/j.kint.2020.05.013

PMID:32554923

Java A, Apicelli AJ, Liszewski MK, Coler-Reilly A, Atkinson JP, Kim AH, Kulkarni HS

The complement system in COVID-19: friend and foe?

JCI Insight 5:140711 (2020)
DOI:10.1172/jci.insight.140711