CYTOKINE RELEASE SYNDROME AND TREATMENT IN COVID-19

Banu Acar

doi:10.12956/tchd.757711

Review

COVID-19’DA SİTOKİN SALINIM SENDROMU VE TEDAVİ YAKLAŞIMLARI

Year 2020, COVID-19, 55 - 59, 24.07.2020

Banu Acar

https://doi.org/10.12956/tchd.757711

Abstract

Yeni ortaya çıkan coronavirus hastalığı 2019 (COVID-19) küresel bir sağlık sorunudur ve pandemi olarak kabul edilmiştir. COVID-19, hastaların çoğunda hafif grip benzeri semptomlara yol açmasına rağmen, hastalık akut solunum sıkıntısı sendromu ve sitokin salınım sendromu gibi sıklıkla ölümcül, ciddi komplikasyonlara neden olabilir. Bu hastalarda lenfositik sitolitik aktivitedeki defektler proinflamatuar sitokin kaskadını tetiklemekte ve “sitokin fırtınasını” başlatmaktadır. Sonuç olarak, dokulara kontrolsüz aktif makrofaj girişine ve hemofagositoza yol açmaktadır. Burada, COVID-19’da konakçı hücrelerin yanıtları, sitokin salınım sendromu ve sitokin fırtınasını durdurmak için tedavi yaklaşımları ele alınmıştır.

Keywords

COVID-19, Sitokin Salınım Sendromu, Sitokin Fırtınası, Tocilizumab

References

1. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395:565–74.
2. Nazinitsky A, Rosenthal KS. Cytokine storms: systemic disasters of infectious diseases. Infect Dis Clin Pract 2010;18:188–92. 3. Behrens EM. Cytokines in cytokine storm syndrome. In: Cron RQ, Behrens EM. Cytokine Storm Syndrome. Cham: Springer International Publishing 2019;197–207.
4. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. bioRxiv 2020; doi: 10.1101/2020.02.12.945576.
5. Maclean OA, Orton R, Singer J, Robertson DL. Response to “On the origin and continuing evolution of SARS-CoV-2”. 2020. http:// virological.org/t/response-to-on-the-origin-and-continuing-evolution-of-sars-cov-2/418 (accessed March 7, 2020)
6. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Feb 18 doi: 10.1016/S2213-2600(20)30076-X.
7. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017;39:529–39.
8. Liu T, Zhang J, Yang Y, Ma H, Li Z, Zhang J, et al. The potential role of IL-6 in monitoring severe case of coronavirus disease 2019. medRxiv 2020; doi: 10.1101/2020.03.01.20029769.
9. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507–13.
10. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323(11): 1061.
11. Yu L, Tong Y, Shen G, Fu A, Lai Y, Zhou X, et al. Immunodepletion with hypoxemia: a potential high risk subtype of coronavirus disease 2019. medRxiv 2020; doi: 10.1101/2020. 03.03.20030650.
12. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020 Feb 18. (Epub ahead of print) doi: 10.1016/S2213-2600(20)30076-X.
13. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
14. Chen L., Liu H.G., Liu W., Liu J., Liu K., Shang J. (Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia) Zhonghua Jie He He Hu Xi Za Zhi.2020;43:E005.
15. Liu J, Li S, Liu J, Liang B, Wang X, Wang H, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. medRxiv 2020; doi: 10.1101/2020.02.16.20023671.
16. Okabayashi T, Kariwa H, Yokota S, Iki S, Indoh T, Yokosawa N, et al. Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections. J Med Virol 2006;78:417–24.
17. Ling W. C-reactive protein levels in the early stage of COVID-19. Med Mal Infect 2020 doi 10.1016/j.medmal.2020.03.007.
18. Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N Engl J Med. 2020 Mar 18 doi: 10.1056/NEJMoa2001282.
19. Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet 2020;395:683-4. 20. Zha L. Impact of corticosteroid treatment in patients with coronavirus disease 2019. Med J Aust. 2020 March 9.
21. Wu C., Chen X., Cai Y., Xia J., Zhou X., Xu S. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 13 doi: 10.1001/jamainternmed.2020.0994.
22. National Health Commission, National Administration of Traditional Chinese Medicine Diagnosis and treatment protocol for novel coronavirus pneumonia (Trial Version 7) Chin Med J. 2020;133 doi: 10.3760/cma.j.issn.0366-6999.2020.0027.
23. Gao J., Tian Z., Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends.2020;14:72–3.
24. Gautret P., Lagier J.C., Parola P., Hoang V.T., Meddeb L., Mailhe M. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20 doi: 10.1016/j.ijantimicag.2020.105949.
25. Devaux C.A., Rolain J.M., Colson P., Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents.2020 Mar 11 doi: 10.1016/j.ijantimicag.2020.105938.
26. Schrezenmeier E., Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Feb 7 doi: 10.1038/s41584-020-0372-x.
27. Mehta P., McAuley D.F., Brown M., Sanchez E., Tattersall R.S., Manson J.J. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:033–4.
28. 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 Mar 3 doi: 10.1007/s00134-020-05991-x.
29. Herold T, Jurinovic V, Arnreich C, Hellmuth JC, von Bergwelt-Baildon M, Klein M, et al. Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients. medRxiv 2020. In press, https://doi.org/10. 1101/2020.04.01.20047381. Accessed April 8, 2020.
30. Xu L, Mao Y, Chen G. Risk factors for severe corona virus disease 2019 (COVID-19) patients: a systematic review and meta analysis. medRxiv 2020:2020.03.30.20047415 doi 10.1101/2020.03.30.20047415.
31. Tanaka T., Narazaki M., Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8:959–70.
32. Xu X.L., Han M.F., Li T.T., Sun W., Wang D.S., Fu B.Q., et al. Effective treatment of severe COVID-19 patients with tocilizumab. ChinaXiv:202003.00026.
33. Kawada J., Kitagawa Y., Iwata N., Ito Y. Clinical characteristics of influenza virus infection in juvenile idiopathic arthritis patients treated with tocilizumab. Mod Rheumatol.2013;23:972–6.
34. Rutherford A.I., Subessinghe S., Hyrich K.L., Galloway J.B. Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2018;77:905–10.
35. Perricone C, Triggianese P, Bartoloni E, Cafaro G, Bonifacio AF, Bursi R, et al. The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19. J Autoimmun. 2020;17:102468. doi: 10.1016/j.jaut.2020.102468.
36. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. bioRxiv 2020; doi: 10.1101/2020.02.12.945576
37. Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of antiinflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol 2020;214:108393 doi 10.1016/j.clim.2020.108393.
38. Zhou G, Chen S, Chen Z. Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies. Front. Med. 2000 https://doi.org/10.1007/s11684-020-0773-x.
39. Lipworth B, Chan R, Lipworth S, RuiWen Kuo C. Weathering the cytokine storm in susceptible patients with severe SARS-CoV-2 infection. J Allergy Clin Immunol Pract. 2020 Apr 17. pii: S2213-2198(20)30365-2. doi: 10.1016/j.jaip.2020.04.014.

CYTOKINE RELEASE SYNDROME AND TREATMENT IN COVID-19

Year 2020, COVID-19, 55 - 59, 24.07.2020

Banu Acar

https://doi.org/10.12956/tchd.757711

Abstract

The emergent outbreak of coronavirus disease 2019 (COVID-19) is a global health problem and has been recognized as a pandemic. Although COVID-19 leads to mild flu-like symptoms in most patients, the disease may cause frequently fatal, severe complications, such as acute respiratory distress syndrome and cytokine release syndrome. In these patients, defects in lymphocytic cytolytic activity trigger the proinflammatory cytokine cascade, and then “cytokine storm” begins. As a result, it leads to uncontrolled active macrophage entry into the tissues and hemophagocytosis. Here, the responses of host cells, cytokine release syndrome and the therapeutic approaches to alleviate the cytokine storm in COVID-19 will be reviewed.

Keywords

Cytokine Release Syndrome, Cytokine Storm, Tocilizumab, COVID-19

References

1. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395:565–74.
2. Nazinitsky A, Rosenthal KS. Cytokine storms: systemic disasters of infectious diseases. Infect Dis Clin Pract 2010;18:188–92. 3. Behrens EM. Cytokines in cytokine storm syndrome. In: Cron RQ, Behrens EM. Cytokine Storm Syndrome. Cham: Springer International Publishing 2019;197–207.
4. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. bioRxiv 2020; doi: 10.1101/2020.02.12.945576.
5. Maclean OA, Orton R, Singer J, Robertson DL. Response to “On the origin and continuing evolution of SARS-CoV-2”. 2020. http:// virological.org/t/response-to-on-the-origin-and-continuing-evolution-of-sars-cov-2/418 (accessed March 7, 2020)
6. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Feb 18 doi: 10.1016/S2213-2600(20)30076-X.
7. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017;39:529–39.
8. Liu T, Zhang J, Yang Y, Ma H, Li Z, Zhang J, et al. The potential role of IL-6 in monitoring severe case of coronavirus disease 2019. medRxiv 2020; doi: 10.1101/2020.03.01.20029769.
9. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507–13.
10. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323(11): 1061.
11. Yu L, Tong Y, Shen G, Fu A, Lai Y, Zhou X, et al. Immunodepletion with hypoxemia: a potential high risk subtype of coronavirus disease 2019. medRxiv 2020; doi: 10.1101/2020. 03.03.20030650.
12. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020 Feb 18. (Epub ahead of print) doi: 10.1016/S2213-2600(20)30076-X.
13. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.
14. Chen L., Liu H.G., Liu W., Liu J., Liu K., Shang J. (Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia) Zhonghua Jie He He Hu Xi Za Zhi.2020;43:E005.
15. Liu J, Li S, Liu J, Liang B, Wang X, Wang H, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. medRxiv 2020; doi: 10.1101/2020.02.16.20023671.
16. Okabayashi T, Kariwa H, Yokota S, Iki S, Indoh T, Yokosawa N, et al. Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections. J Med Virol 2006;78:417–24.
17. Ling W. C-reactive protein levels in the early stage of COVID-19. Med Mal Infect 2020 doi 10.1016/j.medmal.2020.03.007.
18. Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N Engl J Med. 2020 Mar 18 doi: 10.1056/NEJMoa2001282.
19. Shang L, Zhao J, Hu Y, Du R, Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet 2020;395:683-4. 20. Zha L. Impact of corticosteroid treatment in patients with coronavirus disease 2019. Med J Aust. 2020 March 9.
21. Wu C., Chen X., Cai Y., Xia J., Zhou X., Xu S. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020 Mar 13 doi: 10.1001/jamainternmed.2020.0994.
22. National Health Commission, National Administration of Traditional Chinese Medicine Diagnosis and treatment protocol for novel coronavirus pneumonia (Trial Version 7) Chin Med J. 2020;133 doi: 10.3760/cma.j.issn.0366-6999.2020.0027.
23. Gao J., Tian Z., Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends.2020;14:72–3.
24. Gautret P., Lagier J.C., Parola P., Hoang V.T., Meddeb L., Mailhe M. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Mar 20 doi: 10.1016/j.ijantimicag.2020.105949.
25. Devaux C.A., Rolain J.M., Colson P., Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents.2020 Mar 11 doi: 10.1016/j.ijantimicag.2020.105938.
26. Schrezenmeier E., Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Feb 7 doi: 10.1038/s41584-020-0372-x.
27. Mehta P., McAuley D.F., Brown M., Sanchez E., Tattersall R.S., Manson J.J. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:033–4.
28. 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 Mar 3 doi: 10.1007/s00134-020-05991-x.
29. Herold T, Jurinovic V, Arnreich C, Hellmuth JC, von Bergwelt-Baildon M, Klein M, et al. Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients. medRxiv 2020. In press, https://doi.org/10. 1101/2020.04.01.20047381. Accessed April 8, 2020.
30. Xu L, Mao Y, Chen G. Risk factors for severe corona virus disease 2019 (COVID-19) patients: a systematic review and meta analysis. medRxiv 2020:2020.03.30.20047415 doi 10.1101/2020.03.30.20047415.
31. Tanaka T., Narazaki M., Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8:959–70.
32. Xu X.L., Han M.F., Li T.T., Sun W., Wang D.S., Fu B.Q., et al. Effective treatment of severe COVID-19 patients with tocilizumab. ChinaXiv:202003.00026.
33. Kawada J., Kitagawa Y., Iwata N., Ito Y. Clinical characteristics of influenza virus infection in juvenile idiopathic arthritis patients treated with tocilizumab. Mod Rheumatol.2013;23:972–6.
34. Rutherford A.I., Subessinghe S., Hyrich K.L., Galloway J.B. Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2018;77:905–10.
35. Perricone C, Triggianese P, Bartoloni E, Cafaro G, Bonifacio AF, Bursi R, et al. The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19. J Autoimmun. 2020;17:102468. doi: 10.1016/j.jaut.2020.102468.
36. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. bioRxiv 2020; doi: 10.1101/2020.02.12.945576
37. Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of antiinflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol 2020;214:108393 doi 10.1016/j.clim.2020.108393.
38. Zhou G, Chen S, Chen Z. Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies. Front. Med. 2000 https://doi.org/10.1007/s11684-020-0773-x.
39. Lipworth B, Chan R, Lipworth S, RuiWen Kuo C. Weathering the cytokine storm in susceptible patients with severe SARS-CoV-2 infection. J Allergy Clin Immunol Pract. 2020 Apr 17. pii: S2213-2198(20)30365-2. doi: 10.1016/j.jaip.2020.04.014.

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Details

Primary Language	English
Subjects	Internal Diseases
Journal Section	REVIEW
Authors	Banu Acar 0000-0002-1808-3655
Publication Date	July 24, 2020
Submission Date	June 25, 2020
Published in Issue	Year 2020 COVID-19

Cite

Vancouver	Acar B. CYTOKINE RELEASE SYNDROME AND TREATMENT IN COVID-19. Türkiye Çocuk Hast Derg. 2020;14(COVID-19):55-9.

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