Cytokine Storm, Corticosteroids and İnterleukin-6 Receptor Antibodies in Context of Antiinflammatory Treatment in COVID-19
Journal of Pharmaceutical Research International,
Page 67-75
DOI:
10.9734/jpri/2020/v32i2530824
Abstract
It is well established that cytokine storm is associated with more severe clinical course of COVID-19. Many clinical findings of COVID-19 and other severe viral infections (e.g. fever, muscle pain, respiratory distress, cough), are directly attributed to cytokine storm. For example, IL-6 and IL-10 can be used as predictors for expedient diagnosis of patients with higher risk of deterioration. Hyper-inflammatory status in patients with severe COVID-19 is to be mitigated to alleviate signs and symptoms in cytokine storm. In case of deterioration of oxygenation and rapid progression of imaging (CT) findings, glucocorticoids can be used for a short time (3-5 days) for patients in whom overactivation of the body's inflammatory response is suspected. On the other hand, interleukin-6 receptor antibodies tocilizumab, sarilumab, siltuximab can be used as immunomodulators, to suppress inflammation and to alleviate fever and other manifestations of immune response. Their beneficial efficacy is especially remarkable during the cytokine storm period. It should be kept in mind that the agents to be used in the management of any given patient should be tailored for each situation.
Keywords:
- Cytokine storm
- corticosteroids
- interleukin-6 receptor antibodies
- tocilizumab
- antiinflammatory treatment
- COVID-19
How to Cite
Karcioglu, O., Afacan, G., Ozkaya, B., Yilmaz, E., Ersan, E., Yeniocak, S., & Hosseinzadeh, M. (2020). Cytokine Storm, Corticosteroids and İnterleukin-6 Receptor Antibodies in Context of Antiinflammatory Treatment in COVID-19. Journal of Pharmaceutical Research International, 32(25), 67-75. https://doi.org/10.9734/jpri/2020/v32i2530824
References
Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM, Suliman BA. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine. 2018; 104:8-13.
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017; 39(5):529-539.
Han H, Ma Q, Li C, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9(1):1123-1130. doi:10.1080/22221751.2020.1770129
Zeng Z, Yu H, Chen H, et al. Longitudinal changes of inflammatory parameters and their correlation with disease severity and outcomes in patients with COVID-19 from Wuhan, China. Crit Care. 2020;24(1):525. Published 2020 Aug 27.
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. 2020 May;55(5):105954. doi: 10.1016/j.ijantimicag.2020.105954. Epub 2020 Mar 29. PMID: 32234467; PMCID: PMC7118634.
Beigel, JH, Nam HH, Adams PL, Krafft A, et al. Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference. Antiviral Research, 2019; 167: 45-67.
Chu CM, Cheng VCC, Hung IFN, et al. Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax 2004; 59(3): 252–256.
Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst Rev. 2016 Mar 7;3:CD010406. doi: 10.1002/14651858.CD010406.pub2. Update in: Cochrane Database Syst Rev. 2019 Feb 24;2:CD010406. PMID: 26950335.
Arabi YM, Mandourah Y, Al-Hameed F, et al, Saudi Critical Care Trial Group. Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. Am J Respir Crit Care Med. 2018 Mar 15;197(6):757-767. doi: 10.1164/rccm.201706-1172OC.
Zha L, Li S, Pan L, et al. Corticosteroid treatment of patients with coronavirus disease 2019 (COVID‐19). Med J Aust. 2020 May;212(9):416-20.
Micallef J, Soeiro T, Jonville-Béra AP; French Society of Pharmacology, Therapeutics (SFPT). Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection. Therapie. 2020 Jul-Aug;75(4):355-362. doi: 10.1016/j.therap.2020.05.003. Epub 2020 May 7.
Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia inWuhan, China. JAMA Intern Med 2020; 180(7): 1-11.
Laird E, Rhodes J, Kenny RA. Vitamin D and Inflammation: Potential Implications for Severity of Covid-19. Ir Med J. 2020 May 7;113(5):81.
Liu F, Ji C, Luo J, et al. Clinical characteristics and corticosteroids application of different clinical types in patients with corona virus disease 2019. Sci Rep. 2020 Aug 13;10(1):13689. doi: 10.1038/s41598-020-70387-2.
Busani S, Tosi M, Mighali P, et al. Multi-centre, three arm, randomized controlled trial on the use of methylprednisolone and unfractionated heparin in critically ill ventilated patients with pneumonia from SARS-CoV-2 infection: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Aug 17;21(1):724. doi: 10.1186/s13063-020-04645-z.
(Released by National Health Commission & National Administration of Traditional Chinese Medicine on March 3, 2020). Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). Chin Med J (Engl). 2020 May 5;133(9):1087-1095. doi: 10.1097/CM9.0000000000000819. PMID: 32358325; PMCID: PMC7213636.
The 3/4/2020 Chinese Health and Public Health Ministry Guideline on Novel Coronavirus Disease (COVID-19) Diagnosis and Treatment (Revision #6). URL: https://www.kaleidahealth.org/coronavirus/support/literature/Chinese-Health-and-Public-Health-Ministry-Guideline.pdf Accessed: 29.08.2020
WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. 2020. https://www.who. int/docs/default-source/coronaviruse/clinical-management-of-novel-cov. pdf (accessed Feb 20, 2020).
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020 Feb 15;395(10223):473-475. doi: 10.1016/S0140-6736(20)30317-2. Epub 2020 Feb 7. PMID: 32043983; PMCID: PMC7134694.
Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020 Aug 25;324(8):782-793.
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med. 2020 Jul 17:NEJMoa2021436. doi: 10.1056/NEJMoa2021436. Epub ahead of print.
WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020 Sep 2. doi: 10.1001/jama.2020.17023. Epub ahead of print. PMID: 32876694.
Lamontagne F, Agoritsas T, Macdonald H, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020;370:m3379. Published 2020 Sep 4. doi:10.1136/bmj.m3379
Santomasso BD, Park JH, Salloum D, et al. Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov 2018; 8: 958-71.
Pelaia C, Tinello C, Vatrella A, De Sarro G, Pelaia G. Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications. Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620933508.
Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA 2020; 117(20): 10970-5.
Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020 Jul;92(7):814-818.
Toniati P, Piva S, Cattalini M, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev 2020; 19(7): 102568.
Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2020 Aug;2(8):e474-e484.
Meleveedu KS, Miskovsky J, Meharg J, et al Tocilizumab for severe COVID-19 related illness - A community academic medical center experience. Cytokine X. 2020 Dec;2(4):100035.
A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia (COVACTA). URL: https://clinicaltrials.gov/ct2/show/NCT04320615 Accessed: 05.09.2020
Garcia-Vicuña R, Abad-Santos F, González-Alvaro I, Ramos-Lima F, Sanz JS. Subcutaneous Sarilumab in hospitalised patients with moderate-severe COVID-19 infection compared to the standard of care (SARCOVID): a structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21(1):772. Published 2020 Sep 9.
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017; 39(5):529-539.
Han H, Ma Q, Li C, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9(1):1123-1130. doi:10.1080/22221751.2020.1770129
Zeng Z, Yu H, Chen H, et al. Longitudinal changes of inflammatory parameters and their correlation with disease severity and outcomes in patients with COVID-19 from Wuhan, China. Crit Care. 2020;24(1):525. Published 2020 Aug 27.
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. 2020 May;55(5):105954. doi: 10.1016/j.ijantimicag.2020.105954. Epub 2020 Mar 29. PMID: 32234467; PMCID: PMC7118634.
Beigel, JH, Nam HH, Adams PL, Krafft A, et al. Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference. Antiviral Research, 2019; 167: 45-67.
Chu CM, Cheng VCC, Hung IFN, et al. Role of lopinavir/ritonavir in the treatment of SARS: Initial virological and clinical findings. Thorax 2004; 59(3): 252–256.
Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst Rev. 2016 Mar 7;3:CD010406. doi: 10.1002/14651858.CD010406.pub2. Update in: Cochrane Database Syst Rev. 2019 Feb 24;2:CD010406. PMID: 26950335.
Arabi YM, Mandourah Y, Al-Hameed F, et al, Saudi Critical Care Trial Group. Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome. Am J Respir Crit Care Med. 2018 Mar 15;197(6):757-767. doi: 10.1164/rccm.201706-1172OC.
Zha L, Li S, Pan L, et al. Corticosteroid treatment of patients with coronavirus disease 2019 (COVID‐19). Med J Aust. 2020 May;212(9):416-20.
Micallef J, Soeiro T, Jonville-Béra AP; French Society of Pharmacology, Therapeutics (SFPT). Non-steroidal anti-inflammatory drugs, pharmacology, and COVID-19 infection. Therapie. 2020 Jul-Aug;75(4):355-362. doi: 10.1016/j.therap.2020.05.003. Epub 2020 May 7.
Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia inWuhan, China. JAMA Intern Med 2020; 180(7): 1-11.
Laird E, Rhodes J, Kenny RA. Vitamin D and Inflammation: Potential Implications for Severity of Covid-19. Ir Med J. 2020 May 7;113(5):81.
Liu F, Ji C, Luo J, et al. Clinical characteristics and corticosteroids application of different clinical types in patients with corona virus disease 2019. Sci Rep. 2020 Aug 13;10(1):13689. doi: 10.1038/s41598-020-70387-2.
Busani S, Tosi M, Mighali P, et al. Multi-centre, three arm, randomized controlled trial on the use of methylprednisolone and unfractionated heparin in critically ill ventilated patients with pneumonia from SARS-CoV-2 infection: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Aug 17;21(1):724. doi: 10.1186/s13063-020-04645-z.
(Released by National Health Commission & National Administration of Traditional Chinese Medicine on March 3, 2020). Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). Chin Med J (Engl). 2020 May 5;133(9):1087-1095. doi: 10.1097/CM9.0000000000000819. PMID: 32358325; PMCID: PMC7213636.
The 3/4/2020 Chinese Health and Public Health Ministry Guideline on Novel Coronavirus Disease (COVID-19) Diagnosis and Treatment (Revision #6). URL: https://www.kaleidahealth.org/coronavirus/support/literature/Chinese-Health-and-Public-Health-Ministry-Guideline.pdf Accessed: 29.08.2020
WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. 2020. https://www.who. int/docs/default-source/coronaviruse/clinical-management-of-novel-cov. pdf (accessed Feb 20, 2020).
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020 Feb 15;395(10223):473-475. doi: 10.1016/S0140-6736(20)30317-2. Epub 2020 Feb 7. PMID: 32043983; PMCID: PMC7134694.
Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020 Aug 25;324(8):782-793.
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with Covid-19 - Preliminary Report. N Engl J Med. 2020 Jul 17:NEJMoa2021436. doi: 10.1056/NEJMoa2021436. Epub ahead of print.
WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020 Sep 2. doi: 10.1001/jama.2020.17023. Epub ahead of print. PMID: 32876694.
Lamontagne F, Agoritsas T, Macdonald H, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020;370:m3379. Published 2020 Sep 4. doi:10.1136/bmj.m3379
Santomasso BD, Park JH, Salloum D, et al. Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov 2018; 8: 958-71.
Pelaia C, Tinello C, Vatrella A, De Sarro G, Pelaia G. Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications. Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620933508.
Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA 2020; 117(20): 10970-5.
Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020 Jul;92(7):814-818.
Toniati P, Piva S, Cattalini M, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev 2020; 19(7): 102568.
Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2020 Aug;2(8):e474-e484.
Meleveedu KS, Miskovsky J, Meharg J, et al Tocilizumab for severe COVID-19 related illness - A community academic medical center experience. Cytokine X. 2020 Dec;2(4):100035.
A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia (COVACTA). URL: https://clinicaltrials.gov/ct2/show/NCT04320615 Accessed: 05.09.2020
Garcia-Vicuña R, Abad-Santos F, González-Alvaro I, Ramos-Lima F, Sanz JS. Subcutaneous Sarilumab in hospitalised patients with moderate-severe COVID-19 infection compared to the standard of care (SARCOVID): a structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21(1):772. Published 2020 Sep 9.
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