Indian Journal of Critical Care Medicine

Register      Login

SEARCH WITHIN CONTENT

FIND ARTICLE

Volume / Issue

Online First

Archive
Volume  28 (2024)
Volume  27 (2023)
Volume  26 (2022)
Volume  25 (2021)
Volume  24 (2020)
Volume  23 (2019)
Volume  22 (2018)
Volume  21 (2017)
Volume  20 (2016)
Volume  19 (2015)
Volume  18 (2014)
Volume  17 (2013)
Volume  16 (2012)
Volume  15 (2011)
Volume  14 (2010)
Volume  13 (2009)
Volume  12 (2008)
Volume  11 (2007)
Volume  10 (2006)
Volume  9 (2005)
Volume  8 (2004)
Related articles

VOLUME 24 , ISSUE 6 ( June, 2020 ) > List of Articles

REVIEW ARTICLE

Cytokine Storm in Novel Coronavirus Disease (COVID-19): Expert Management Considerations

Abdul S Ansari

Citation Information : Ansari AS. Cytokine Storm in Novel Coronavirus Disease (COVID-19): Expert Management Considerations. Indian J Crit Care Med 2020; 24 (6):429-434.

DOI: 10.5005/jp-journals-10071-23415

License: CC BY-NC 4.0

Published Online: 22-10-2020

Copyright Statement:  Copyright © 2020; The Author(s).


Abstract

Aim/objective/introduction: Cytokine storm or cytokine release syndrome (CRS) is inevitable in severe and critically ill patients with novel coronavirus disease-2019 (COVID-19). This review aimed to discuss current therapeutic options for the management of CRS in COVID-19. Background: Cytokine storm is caused by the colossal release of proinflammatory cytokines [e.g., IL (interleukin)-2, IL-6, IL-8 TNF (tumor necrosis factor)-α, etc.] causing dysregulated, hyperimmune response. This immunopathogenesis leads to acute lung injury and acute respiratory distress syndrome (ARDS). Targeting cytokine storm with the therapies that are already available in India with the support of published guidelines and consensus can assist in achieving a better outcome in COVID-19. Review results: We predominantly included published guidelines or consensus recommendations about the management of cytokine storm in COVID-19. From the existing literature evidence, it is observed that among the currently available agents, low-dose corticosteroids and heparin can be beneficial in managing cytokine storm. The use of serine protease inhibitors such as ulinastatin has been advised by some experts. Though therapies such as high-dose vitamin C and interleukin-6 inhibitors (e.g., tocilizumab) have been advised, the evidence regarding their use for cytokine storm in COVID-19 is limited. Therapies such as Janus kinase inhibitors (JAK) inhibitors and Neurokinin-1 receptor (NK-1) antagonists are still in research. Besides, pharmaceutical treatments, use of blood purification strategies, and convalescent plasma may be life-saving options in some of the critically ill COVID-19 patients. For these therapies, there is a need to generate further evidence to substantiate their use in CRS management. Conclusion: Current management of COVID-19 is preventive and supportive. Different therapies can be used to prevent and treat the cytokine storm. More research is needed for further supporting the use of these treatments in COVID-19.

HTML PDF Share
  1. https://www.who.int/emergencies/diseases/novel-coronavirus-2019 [Accessed on 14th April 2020].
  2. https://www.mohfw.gov.in/. [Accessed on 14th April 2020].
  3. World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected Interim guidance 13 March 2020. Available from https://www.who.int/docs/default-source/coronaviruse/clinical-management-of-novel-cov.pdf.
  4. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published correction appears in Lancet Respir Med 2020;8(4):e26]. Lancet Respir Med 2020;8(5):475–481. doi:10.1016/S2213-2600(20)30079-5.
  5. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017;39(5):529–539. DOI: 10.1007/s00281-017-0629-x.
  6. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395(10229):1033–1034. DOI: 10.1016/S0140-6736(20)30628-0.
  7. Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother 2020;dkaa114. DOI: 10.1093/jac/dkaa114. [published online ahead of print, 2020 Mar 20].
  8. Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. Coronavirus infections and immune responses. J Med Virol 2020;92(4):424–432. DOI: 10.1002/jmv.25685.
  9. Shi Y, Wnag Y, Shao C, Huang J, Gan J, Huang X, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ 2020;27(5):1451–1454. DOI: 10.1038/s41418-020-0530-3.
  10. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020. 1–3. DOI: 10.1007/s00134-020-05991-x.
  11. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18(4):844–847. DOI: 10.1111/jth.14768.
  12. Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med 2020. S2213-2600(20)30216-2. DOI: 1016/S2213-2600(20)30216-2.
  13. Fardet L, Galicier L, Lambotte O, Marzac C, Aumont C, Chahwan D, et al. Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol 2014;66(9):2613–2620. DOI: 10.1002/art.38690.
  14. Gerlach H. Agents to reduce cytokine storm. F1000Res 2016;5:2909. DOI: 10.12688/f1000research.9092.1.
  15. Wu C, Chen X, Cai Y, Zhou X, Xu S, Huang H, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020. e200994. DOI: 10.1001/jamainternmed.2020.0994.
  16. Lian XJ, Huang DZ, Cao YS, Wei YX, Lian ZZ, Qin TH, et al. Reevaluating the role of corticosteroids in septic shock: an updated meta-analysis of randomized controlled trials. Biomed Res Int 2019. 3175047. DOI: 10.1155/2019/3175047.
  17. Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19). Intensive Care Med 2020. 1–34. DOI: 10.1007/s00134-020-06022-5.
  18. Kalil AC. Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during pandemics. JAMA 2020. DOI: 10.1001/jama.2020.4742. [published online ahead of print, 2020 Mar 24].
  19. Shanghai Novel Coronavirus Disease Clinical Treatment Expert Group. Expert consensus on comprehensive treatment of coronavirus disease in Shanghai 2019. Chin J Infect Dis 2020. 38. DOI: 10.3760/cma.j.issn.1000-6680.2020.0016.
  20. Russell B, Moss C, George G, Santaolalla A, Cope A, Papa S, et al. Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience. 2020;14:1022. DOI: 10.3332/ecancer. 2020.1022.
  21. Fowler III AF, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI randomized clinical trial. JAMA 2019;322(13):1261–1270. DOI: 10.1001/jama.2019.11825.
  22. Thachil J. The versatile heparin in COVID-19. J Thromb Haemost 2020;18(5):1020–1022. DOI: 10.1111/jth.14821.
  23. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18(5): 1094–1099. DOI: 10.1111/jth.14817.
  24. Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost 2020;18(5):1023–1026. DOI: 10.1111/jth.14810.
  25. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181(2):280. DOI: 10.1016/j.cell.2020.02.052.
  26. Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion Jr R, Nunneley JW, et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res 2015;116:76–84. DOI: 10.1016/j.antiviral.2015.01.011.
  27. Yamamoto M, Matsuyama S, Li X, Takeda M, Kawaguchi Y, Inoue JI, et al. Identification of Nafamostat as a potent inhibitor of Middle East respiratory syndrome coronavirus S protein-mediated membrane fusion using the split-protein-based cell-cell fusion assay. Antimicrob Agents Chemother 2016;60(11):6532–6539. DOI: 10.1128/AAC. 01043-16.
  28. Zhang X, Zhu Z, Jiao W, Liu W, Liu F, Zhu X. Ulinastatin treatment for acute respiratory distress syndrome in China: a meta-analysis of randomized controlled trials. BMC Pulm Med 2019;19(1):196. DOI: 10.1186/s12890-019-0968-6.
  29. Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA 2020;323(16):1582–1589. DOI: 10.1001/jama.2020.4783.
  30. Investigational COVID-19 Convalescent Plasma. Guidance for Industry. U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research April 2020. https://www.fda.gov/media/136798/download.
  31. Zhang Y, Yu L, Tang L, Zhu M, Jin Y, Wang Z, et al. A promising anti-cytokine-storm targeted therapy for COVID-19: the artificial-liver blood-purification system. Engineering (Beijing) 2020. DOI: 10.1016/j.eng.2020.03.006. [published online ahead of print, 2020 Mar 20].
  32. Burgner A, Alp Ikizler T, Dwyer JP. COVID-19 and the inpatient dialysis unit managing resources during contingency planning pre-crisis. Clin J Am Soc Nephrol 2020. CJN.03750320. DOI: 10.2215/CJN.03750320.
  33. https://cytosorb-therapy.com/en/covid-19/. [Accessed on 11th April 2020].
  34. Bergman SJ, Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies. 2020 Apr 10. https://emedicine.medscape.com/article/2500116-overview.
  35. Roche initiates Phase III clinical trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 pneumonia. https://www.roche.com/media/releases/med-cor-2020-03-19.htm.
  36. Zhang W, Zhao Y, Zhang F, Wang Q, Taisheng L, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the experience of clinical immunologists from China. Clin Immunol 2020;214:108393. DOI: 10.1016/j.clim.2020.108393.
  37. Government of India Ministry of Health & Family Welfare Directorate General of Health Services (EMR Division) Guidelines on Clinical Management of COVID –19. 17th March 2020. Available from https://www.mohfw.gov.in/pdf/Guidelineson ClinicalManagementofCOVID1912020.pdf.
  38. Mehta Y, Chaudhry D, Abraham OC, Chacko J, Divatia J, Jagiasi B, et al. Critical care for COVID-19 affected patients: position statement of the Indian Society of Critical Care Medicine. Indian J Crit Care Med 2020. DOI: 10.5005/jp-journals-10071-23395.
  39. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J Infect 2020. S0163-4453(20)30165-1. DOI: 10.1016/j.jinf.2020.03.037.
  40. Sun X, Wang T, Cai D, Hu Z, Chen J, Liao H, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev 2020. S1359-6101(20)30048-4. DOI: 10.1016/j.cytogfr.2020.04.002.
  41. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for Coronavirus Disease 2019 (COVID-19) a review. JAMA 2020. DOI: 10.1001/jama.2020.6019. [published online ahead of print, 2020 Apr 13].
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.