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* <s>There have been reports on an association between cytokine storm and severity of [[COVID-19]] infection and COVID-19-associated-ARDS.</s>
* <s>There have been reports on an association between cytokine storm and severity of [[COVID-19]] infection and COVID-19-associated-ARDS.</s>


*It has been suggested that  the [[pathogenesis]] of severe [[COVID-19]] infection may be due to cytokine storm and suppression of [[T helper cell|Th1]] antiviral responses since the following findings have been reported to be associated with severe [[COVID-19]] infection: (kupalli)
*It has been suggested that  the [[pathogenesis]] of severe [[COVID-19]] infection may be due to cytokine storm and suppression of [[T helper cell|Th1]] antiviral responses since the following findings have been reported to be associated with severe [[COVID-19]] infection:<ref name="pmid32361250">{{cite journal| author=Liu J, Li S, Liu J, Liang B, Wang X, Wang H | display-authors=etal| title=Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. | journal=EBioMedicine | year= 2020 | volume= 55 | issue=  | pages= 102763 | pmid=32361250 | doi=10.1016/j.ebiom.2020.102763 | pmc=7165294 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32361250  }} </ref><ref name="pmid32388462">{{cite journal| author=Kuppalli K, Rasmussen AL| title=A glimpse into the eye of the COVID-19 cytokine storm. | journal=EBioMedicine | year= 2020 | volume= 55 | issue=  | pages= 102789 | pmid=32388462 | doi=10.1016/j.ebiom.2020.102789 | pmc=7204696 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32388462  }} </ref>
**Increase in pro-inflammatory [[Cytokine|cytokines]] (such as [[Interleukin 6|IL-6]])
**Increase in pro-inflammatory [[Cytokine|cytokines]] (such as [[Interleukin 6|IL-6]])
**Increase in [[Interleukin 10|IL-10]] (a [[cytokine]] produced by  [[T helper cell|Th2]]) and suppression in [[T helper cell|Th1]] antiviral responses
**Increase in [[Interleukin 10|IL-10]] (a [[cytokine]] produced by  [[T helper cell|Th2]]) and suppression in [[T helper cell|Th1]] antiviral responses

Revision as of 18:37, 11 July 2020

Associate Editor(s)-in-Chief: Shakiba Hassanzadeh, MD[1]


Cytokine storm is an immune reaction that is characterized by dysregulated and excessive release of proinflammatory cytokines.[1]

Cytokines Involved in Cytokine Storm

Pathogenesis of Cytokine Storm

  • Cytokine storm is an immune reaction that is characterized by dysregulated and excessive release of proinflammatory cytokines.[1]
  • During sepsis, cytokine storm may be the cause of tissue or organ injury.[2]
  • It has been suggested that the pathogenesis of severe COVID-19 infection may be due to cytokine storm and suppression of Th1 antiviral responses since the following findings have been reported to be associated with severe COVID-19 infection:[8][9]
Cytokines Involved in COVID-19-Associated-Cytokine Storm
Proinflammatory Interferones
  • IFN-γ
Interleukines
  • IL-1β
  • IL-6
Chemokines
  • CCL-2 (MCP-1)
  • CCL-3 (Macrophage inflammatory protein-1A)
  • CCL-5
  • IL-8 (CXCL8)
  • IP-10 (CXCL10)
Colony-stimulating

factors  

  • GM-CSF
Tumor necrosis

factor  

  • TNF-α
Anti-inflammatory Interleukines
  • IL-4
  • IL-10




Overview

COVID-19-Associated Hematologic Findings

Pathophysiology and Causes

Epidemiology

  • Leukocytosis is seen in 11.4% of patients with severe COVID-19 infection compared to 4.8% of patients with non-severe infection.[12][13]
  • Increase in CRP is seen in 81.5% of patients with severe COVID-19 infection compared to 56.4% of patients with non-severe infection.[12][13]
  • Increase in procalcitonin is seen in 13.7% of patients with severe COVID-19 infection compared to 3.7% of patients with non-severe infection.[12][13]
  • Increase in AST is seen in 39.4% of patients with severe COVID-19 infection compared to 18.2% of patients with non-severe infection.[12][13]
  • Increase in ALT is seen in 28.1% of patients with severe COVID-19 infection compared to 19.8% of patients with non-severe infection.[12][13]
  • Increase in LDH is seen in 58.1% of patients with severe COVID-19 infection compared to 37.2% of patients with non-severe infection.[12][13]
  • MDW was found to be increased in all patients with COVID-19 infection, particularly in those with the worst conditions.[13]
  • Increase in total bilirubin is seen in 13.3% of patients with severe COVID-19 infection compared to 9.9% of patients with non-severe infection.[12][13]
  • Increase in creatinine is seen in 4.3% of patients with severe COVID-19 infection compared to 1% of patients with non-severe infection.[12][13]
  • Thrombocytosis has been reported in 4% of patients with COVID-19 infection.[14]

Clinical Significance

Laboratory findings in COVID-19 infection may indicate clinical abnormalities, including:

  • In patients with COVID-19 infection, leukocytosis may be an indication of a bacterial infection or superinfection.[13]
  • In patients with COVID-19 infection, increase in CRP may be an indication of severe viral infection or sepsis and viremia.[13]
  • In patients with COVID-19 infection, increase in procalcitonin may be an indication of bacterial infection or superinfection.[13]
  • There have been different reports regarding the association of increase in ferritin with death in COVID-19 infection; for example, there has been a report that increase in ferritin is associated with acute respiratory distress syndrome (ARDS) but not death[15], while another one reports an association between increase in ferritin and death in COVID-19 infection[16]
  • In patients with COVID-19 infection, increase in aminotransferases may indicate injury to the liver or multi-system damage.[13]
  • In patients with COVID-19 infection, increase in aminotransferases may indicate injury to the liver or multi-system damage.[13]
  • In patients with COVID-19 infection, increase in LDH may indicate injury to the lungs or multi-system damage.[13]
  • In patients with COVID-19 infection, increase in total bilirubin may indicate injury to the liver.[13]
  • In patients with COVID-19 infection, increase in creatinine may indicate injury to the kidneys.[13]
  • In patients with COVID-19 infection, increase in cardiac troponins may indicate cardiac injury.[13]
  • In patients with COVID-19 infection, decrease in albumin may indicate liver function abnormality.[13]
  • Increase in IL-6 has been reported to be associated with death in COVID-19 infection.[15]


References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG (2012). "Into the eye of the cytokine storm". Microbiol Mol Biol Rev. 76 (1): 16–32. doi:10.1128/MMBR.05015-11. PMC 3294426. PMID 22390970.
  2. Chousterman BG, Swirski FK, Weber GF (2017). "Cytokine storm and sepsis disease pathogenesis". Semin Immunopathol. 39 (5): 517–528. doi:10.1007/s00281-017-0639-8. PMID 28555385.
  3. Jiang Y, Xu J, Zhou C, Wu Z, Zhong S, Liu J; et al. (2005). "Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome". Am J Respir Crit Care Med. 171 (8): 850–7. doi:10.1164/rccm.200407-857OC. PMID 15657466.
  4. Cameron MJ, Bermejo-Martin JF, Danesh A, Muller MP, Kelvin DJ (2008). "Human immunopathogenesis of severe acute respiratory syndrome (SARS)". Virus Res. 133 (1): 13–9. doi:10.1016/j.virusres.2007.02.014. PMC 7114310 Check |pmc= value (help). PMID 17374415.
  5. Reghunathan R, Jayapal M, Hsu LY, Chng HH, Tai D, Leung BP; et al. (2005). "Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome". BMC Immunol. 6: 2. doi:10.1186/1471-2172-6-2. PMC 546205. PMID 15655079.
  6. Ye Q, Wang B, Mao J (2020). "The pathogenesis and treatment of the `Cytokine Storm' in COVID-19". J Infect. 80 (6): 607–613. doi:10.1016/j.jinf.2020.03.037. PMC 7194613 Check |pmc= value (help). PMID 32283152 Check |pmid= value (help).
  7. Channappanavar R, Perlman S (2017). "Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology". Semin Immunopathol. 39 (5): 529–539. doi:10.1007/s00281-017-0629-x. PMC 7079893 Check |pmc= value (help). PMID 28466096.
  8. Liu J, Li S, Liu J, Liang B, Wang X, Wang H; et al. (2020). "Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients". EBioMedicine. 55: 102763. doi:10.1016/j.ebiom.2020.102763. PMC 7165294 Check |pmc= value (help). PMID 32361250 Check |pmid= value (help).
  9. Kuppalli K, Rasmussen AL (2020). "A glimpse into the eye of the COVID-19 cytokine storm". EBioMedicine. 55: 102789. doi:10.1016/j.ebiom.2020.102789. PMC 7204696 Check |pmc= value (help). PMID 32388462 Check |pmid= value (help).
  10. 10.0 10.1 10.2 10.3 10.4 10.5 10.6 Frater JL, Zini G, d'Onofrio G, Rogers HJ (2020). "COVID-19 and the clinical hematology laboratory". Int J Lab Hematol. 42 Suppl 1: 11–18. doi:10.1111/ijlh.13229. PMC 7264622 Check |pmc= value (help). PMID 32311826 Check |pmid= value (help).
  11. Meisner M (2014). "Update on procalcitonin measurements". Ann Lab Med. 34 (4): 263–73. doi:10.3343/alm.2014.34.4.263. PMC 4071182. PMID 24982830.
  12. 12.0 12.1 12.2 12.3 12.4 12.5 12.6 12.7
  13. 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 13.10 13.11 13.12 13.13 13.14 13.15 13.16 13.17 13.18 Lippi G, Plebani M (2020). "The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks". Clin Chem Lab Med. 58 (7): 1063–1069. doi:10.1515/cclm-2020-0240. PMID 32191623 Check |pmid= value (help).
  14. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y; et al. (2020). "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study". Lancet. 395 (10223): 507–513. doi:10.1016/S0140-6736(20)30211-7. PMC 7135076 Check |pmc= value (help). PMID 32007143 Check |pmid= value (help).
  15. 15.0 15.1 Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S; et al. (2020). "Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China". JAMA Intern Med. doi:10.1001/jamainternmed.2020.0994. PMC 7070509 Check |pmc= value (help). PMID 32167524 Check |pmid= value (help).
  16. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z; et al. (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. PMC 7270627 Check |pmc= value (help). PMID 32171076 Check |pmid= value (help).


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