Critical Clinical Presentation : The Cytokine Storm Syndrome

117 views 3 04/11/2020 04/13/2020 and

Before COVID-19 

  1. Cytokine storm, also known as secondary haemophagocytic lymphohistiocytosis (sHLH), refers to an hyperinflammation state of excessive and uncontrolled release of pro-inflammatory cytokine (interferons, interleukins, chemokines, colony-stimulating factors and tumor necrosis factors) which regulate immune and inflammatory responses
  2. sHLH can be caused by a variety of infectious agents, such as Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis, influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) 
  3. sHLH can cause acute lung injury or acute respiratory distress syndrome
  4. HScores can be use to help diagnose sHLH. A score greater than 169 are 93% sensitive and 86% specific for HLH. 
  5. Genetics play an important role in host susceptibily to sHLH during infection  

Since COVID-19 outbreak

  1. Patients with COVID-19 severe disease can develop a cytokine profile similar to sHLH
  2. All patients with a severe presentation of COVID-19 should have laboratory tests to rule out hyperinflammation (eg, ferritin, platelet counts, or erythrocyte sedimentation rate). 
  3. IP-10, MCP-3, IL-1ra were significantly related to disease severity and progression.  Ferritin and IL-6 levels were also predictors of fatality among confirmed COVID-19 cases.
  4. Immunosuppression therapy including steroids, intravenous immunoglobulin, selective cytokine blockade (e.g: Tocilizumab and anakinra) and JAK inhibition could improve mortality for a subgroup of patients with with cytokine storm associated COVID-19. 

 

This data comes from multiple studies. Huang C., et al. (Lancet) which characterize the cytokines production in 41 patients infected with severe COVID-19. Yang Y. et al. did a retrospective study including 53 patients with confirmed COVID-19 in China to study the difference of cytokines profiles between cases. Two reviews (Mehta P., et al and Zhang W., et al.) give an immunologic perspective on the cytokine storm syndrome and the possible immunosuppression therapy. Karakike E. et al. did a systematic review on the proportion of patients with sepsis developing pro-inflammatory mechanisms of organ dysfunction. 

 

Sources

  1. Huang C., Wang Y., Li X., et al (February 15 2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. https://doi.org/10.1016/S0140-6736(20)30183-5
  2. Karakike E. et Giamarellos-Bourboulis E. J. (January 31, 2019). Macrophage activation-like syndrome: a distinct entity leading to early death in sepsis. Front Immunol 2019. https://doi.org/10.3389/fimmu.2019.00055 
  3. Mehta P., McAuley D.F., Brown M., et al (March 13, 2020). COVID-19: consider cytokine storm syndromes and immunosupression. The Lancet. https://doi.org/10.1016/S0140-6736(20)30628-0 
  4. Yang Y., Shen C., Li J., et al ( March 6, 2020). Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome. MedRxiv. https://doi.org/10.1101/2020.03.02.20029975 
  5. Zhang W., Zhao Y., Zhang F., et al (March 23 2020). The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clinical Immunology https://doi.org/10.1016/j.clim.2020.108393 
  6. Tisoncik J., Korth M., Simmons C., et al (March 2012). Into the eye of the cytokine storm. Microbiology and molecular biology reviews. https://doi.org/10.1128/MMBR.05015-11 

 

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