Research Article
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Year 2022, Volume: 35 Issue: 3, 308 - 315, 31.10.2022

Leman Delen Umut Sabri Kasapoglu Abdullah Gok Ozlem Cagasar Bora Tetık Ersoy Oksuz

https://doi.org/10.5472/marumj.1191126

Abstract

References

  • Chakraborty C, Sharma AR, Sharma G, Bhattacharya M, Lee SS. SARS-CoV-2 causing pneumonia-associated respiratory disorder (COVID-19): diagnostic and proposed therapeutic options. Eur Rev Med Pharmacol Sci 2020;24:4016-26. doi:10.26355/eurrev_202004_20871
  • Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients ınfected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA 2020;323:1574-81. doi:10.1001/jama.2020.5394
  • Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA 2020;323:2052-9. doi:10.1001/jama.2020.6775
  • Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. doi:10.1016/s0140-6736(20)30566-3
  • Bonam SR, Kaveri SV, Sakuntabhai A, Gilardin L, Bayry J. Adjunct immunotherapies for the management of severely ıll COVID-19 patients. Cell Rep Med 2020;1:100016. doi:10.1016/j.xcrm.2020.100016
  • Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506. doi:10.1016/s0140-6736(20)30183-5
  • Odabasi Z, Cinel I. Consideration of severe coronavirus disease 2019 as viral sepsis and potential use of ımmune checkpoint ınhibitors. Crit Care Explor 2020;2:e0141. doi:10.1097/CCE.000.000.0000000141
  • Sun X, Wang T, Cai D, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev 2020;53:38-42. doi:10.1016/j.cytogfr.2020.04.002
  • Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect 2020;80:607-13. doi:10.1016/j.jinf.2020.03.037
  • Kewan T, Covut F, Al-Jaghbeer MJ, Rose L, Gopalakrishna KV, Akbik B. Tocilizumab for treatment of patients with severe COVID-19: A retrospective cohort study. EClinicalMedicine 2020;24:100418. doi:10.1016/j.eclinm.2020.100418
  • 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;92:814-8. doi:10.1002/jmv.25801
  • Mehta N, Mazer-Amirshahi M, Alkindi N, Pourmand A. Pharmacotherapy in COVID-19; A narrative review for emergency providers. Am J Emerg Med 2020;38:1488-93. doi:10.1016/j.ajem.2020.04.035
  • 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;19:102568. doi:10.1016/j.autrev.2020.102568
  • Furlow B. COVACTA trial raises questions about tocilizumab’s benefit in COVID-19. Lancet Rheumatol 2020;2:e592. doi:10.1016/s2665-9913(20)30313-1
  • Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med 2020;383:2333-44. doi:10.1056/NEJMoa2028836
  • Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-29.
  • Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsisrelated Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22:707-10. doi:10.1007/bf01709751
  • Qin C, Zhou L, Hu Z, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020;71:762-8. doi:10.1093/cid/ciaa248
  • Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol 2020;11:1446. doi:10.3389/fimmu.2020.01446
  • Wang W, Liu X, Wu S, et al. Definition and risks of cytokine release syndrome in 11 critically ıll COVID-19 patients with pneumonia: analysis of disease characteristics. J Infect Dis 2020;222:1444-51. doi:10.1093/infdis/jiaa387
  • Lau SKP, Lau CCY, Chan KH, et al. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J Gen Virol 2013;94:2679-90. doi:10.1099/vir.0.055533-0
  • Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017;39:529-39. doi:10.1007/s00281.017.0629-x
  • Liu F, Li L, Xu M, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol 2020;127:104370. doi:10.1016/j. jcv.2020.104370
  • Liu T, Zhang J, Yang Y, et al. The role of interleukin-6 in monitoring severe case of coronavirus disease 2019. EMBO Mol Med 2020;12:e12421. doi:10.15252/emmm.202012421
  • 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 in Wuhan, China. JAMA Intern Med 2020;180:934-43. doi:10.1001/ jamainternmed.2020.0994
  • Borrega J G, Godel P, Rüger MA, et al. In the eye of the storm: ımmune-mediated toxicities associated with CAR-T cell therapy. Hemasphere. 2019;3:e191. doi:10.1097/ HS9.000.000.0000000191
  • Lohse A, Klopfenstein T, Balblanc JC, et al. Predictive factors of mortality in patients treated with tocilizumab for acute respiratory distress syndrome related to coronavirus disease 2019 (COVID-19). Microbes Infect 2020;22:500-3. doi:10.1016/j.micinf.2020.06.005
  • McElvaney OJ, McEvoy NL, McElvaney OF, et al. Characterization of the Inflammatory Response to Severe COVID-19 Illness. Am J Respir Crit Care Med 2020;202:812- 21. doi:10.1164/rccm.202.005.1583OC
  • Tan L, Wang Q, Zhang D, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther 2020;5:33. doi:10.1038/ s41392.020.0148-4
  • Zheng M, Gao Y, Wang G, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol 2020;17:533-5. doi:10.1038/s41423.020.0402-2
  • Alattar R, Ibrahim TBH, Shaar SH, et al. Tocilizumab for the treatment of severe coronavirus disease 2019. J Med Virol 2020;92:2042-9. doi:10.1002/jmv.25964
  • Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with covid-19 pneumonia. N Engl J Med 2021;384:20-30. doi:10.1056/NEJMoa2030340
  • Zhao M. Cytokine storm and immunomodulatory therapy in COVID-19: Role of chloroquine and anti-IL-6 monoclonal antibodies. Int J Antimicrob Agents 2020;55:105982. doi:10.1016/j.ijantimicag.2020.105982
  • Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol 2020;2:e474-e84. doi:10.1016/s2665- 9913(20)30173-9
  • Tleyjeh IM, Kashour Z, Damlaj M, et al. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis. Clin Microbiol Infect 2021;27:215-27. doi:10.1016/j.cmi.2020.10.036
  • RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 : a randomised, controlled, open-label, platform trial. Lancet 2021;397:1637- 45. doi:10.1016/s0140-6736(21)00676-0

Efficacy of tocilizumab therapy in severe COVID-19 pneumonia patients and determination of the prognostic factors affecting 30 days mortality

Year 2022, Volume: 35 Issue: 3, 308 - 315, 31.10.2022

Leman Delen Umut Sabri Kasapoglu Abdullah Gok Ozlem Cagasar Bora Tetık Ersoy Oksuz

https://doi.org/10.5472/marumj.1191126

Abstract

Objective: In coronavirus disease – 19 (COVID-19) patients, cytokine storm develops due to the increase of pro-inflammatory
cytokines. Tocilizumab (TCZ), has been used in the treatment of COVID-19 patients and successful results have been obtained. The
aim of this study was to determine the efficacy of TCZ and also investigate the prognostic factors affecting the success of treatment
and mortality in COVID-19 patients treated with TCZ.
Patients and Methods: Between March 2020 and August 2021, a total of 326 confirmed severe COVID-19 pneumonia patients, treated
in the intensive care unit, were included in the study.
Results: The mean age of the patients was 63.02±11.58 years, and 203 (62.3%) of the patients were male. Patients treated with TCZ
therapy had a longer survival time compared with the standard therapy (p=0.012). It was found that type of respiratory support
(HR:2.19, CI:1.10-4.36, p=0.025) and hyperlactatemia on the day of TCZ therapy admission (HR:2.93 CI:1.53-5.64, p=0.001) were the
significant and independent prognostic factors of survival in severe COVID-19 pneumonia patients treated with TCZ.
Conclusion: Tocilizumab therapy improved 30-days survival in critically ill COVID-19 pneumonia patients. Also, among the patients
treated with TCZ, types of respiratory support and hyperlactatemia on the day of TCZ admission were the independent prognostic
factors.

Keywords

SARS-CoV-2 COVID-19 Tocilizumab Viral pneumonia Cytokine storm Prognostic factors

References

  • Chakraborty C, Sharma AR, Sharma G, Bhattacharya M, Lee SS. SARS-CoV-2 causing pneumonia-associated respiratory disorder (COVID-19): diagnostic and proposed therapeutic options. Eur Rev Med Pharmacol Sci 2020;24:4016-26. doi:10.26355/eurrev_202004_20871
  • Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients ınfected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA 2020;323:1574-81. doi:10.1001/jama.2020.5394
  • Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA 2020;323:2052-9. doi:10.1001/jama.2020.6775
  • Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. doi:10.1016/s0140-6736(20)30566-3
  • Bonam SR, Kaveri SV, Sakuntabhai A, Gilardin L, Bayry J. Adjunct immunotherapies for the management of severely ıll COVID-19 patients. Cell Rep Med 2020;1:100016. doi:10.1016/j.xcrm.2020.100016
  • Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506. doi:10.1016/s0140-6736(20)30183-5
  • Odabasi Z, Cinel I. Consideration of severe coronavirus disease 2019 as viral sepsis and potential use of ımmune checkpoint ınhibitors. Crit Care Explor 2020;2:e0141. doi:10.1097/CCE.000.000.0000000141
  • Sun X, Wang T, Cai D, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev 2020;53:38-42. doi:10.1016/j.cytogfr.2020.04.002
  • Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect 2020;80:607-13. doi:10.1016/j.jinf.2020.03.037
  • Kewan T, Covut F, Al-Jaghbeer MJ, Rose L, Gopalakrishna KV, Akbik B. Tocilizumab for treatment of patients with severe COVID-19: A retrospective cohort study. EClinicalMedicine 2020;24:100418. doi:10.1016/j.eclinm.2020.100418
  • 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;92:814-8. doi:10.1002/jmv.25801
  • Mehta N, Mazer-Amirshahi M, Alkindi N, Pourmand A. Pharmacotherapy in COVID-19; A narrative review for emergency providers. Am J Emerg Med 2020;38:1488-93. doi:10.1016/j.ajem.2020.04.035
  • 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;19:102568. doi:10.1016/j.autrev.2020.102568
  • Furlow B. COVACTA trial raises questions about tocilizumab’s benefit in COVID-19. Lancet Rheumatol 2020;2:e592. doi:10.1016/s2665-9913(20)30313-1
  • Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med 2020;383:2333-44. doi:10.1056/NEJMoa2028836
  • Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-29.
  • Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsisrelated Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22:707-10. doi:10.1007/bf01709751
  • Qin C, Zhou L, Hu Z, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020;71:762-8. doi:10.1093/cid/ciaa248
  • Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol 2020;11:1446. doi:10.3389/fimmu.2020.01446
  • Wang W, Liu X, Wu S, et al. Definition and risks of cytokine release syndrome in 11 critically ıll COVID-19 patients with pneumonia: analysis of disease characteristics. J Infect Dis 2020;222:1444-51. doi:10.1093/infdis/jiaa387
  • Lau SKP, Lau CCY, Chan KH, et al. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J Gen Virol 2013;94:2679-90. doi:10.1099/vir.0.055533-0
  • Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017;39:529-39. doi:10.1007/s00281.017.0629-x
  • Liu F, Li L, Xu M, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol 2020;127:104370. doi:10.1016/j. jcv.2020.104370
  • Liu T, Zhang J, Yang Y, et al. The role of interleukin-6 in monitoring severe case of coronavirus disease 2019. EMBO Mol Med 2020;12:e12421. doi:10.15252/emmm.202012421
  • 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 in Wuhan, China. JAMA Intern Med 2020;180:934-43. doi:10.1001/ jamainternmed.2020.0994
  • Borrega J G, Godel P, Rüger MA, et al. In the eye of the storm: ımmune-mediated toxicities associated with CAR-T cell therapy. Hemasphere. 2019;3:e191. doi:10.1097/ HS9.000.000.0000000191
  • Lohse A, Klopfenstein T, Balblanc JC, et al. Predictive factors of mortality in patients treated with tocilizumab for acute respiratory distress syndrome related to coronavirus disease 2019 (COVID-19). Microbes Infect 2020;22:500-3. doi:10.1016/j.micinf.2020.06.005
  • McElvaney OJ, McEvoy NL, McElvaney OF, et al. Characterization of the Inflammatory Response to Severe COVID-19 Illness. Am J Respir Crit Care Med 2020;202:812- 21. doi:10.1164/rccm.202.005.1583OC
  • Tan L, Wang Q, Zhang D, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther 2020;5:33. doi:10.1038/ s41392.020.0148-4
  • Zheng M, Gao Y, Wang G, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol 2020;17:533-5. doi:10.1038/s41423.020.0402-2
  • Alattar R, Ibrahim TBH, Shaar SH, et al. Tocilizumab for the treatment of severe coronavirus disease 2019. J Med Virol 2020;92:2042-9. doi:10.1002/jmv.25964
  • Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with covid-19 pneumonia. N Engl J Med 2021;384:20-30. doi:10.1056/NEJMoa2030340
  • Zhao M. Cytokine storm and immunomodulatory therapy in COVID-19: Role of chloroquine and anti-IL-6 monoclonal antibodies. Int J Antimicrob Agents 2020;55:105982. doi:10.1016/j.ijantimicag.2020.105982
  • Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol 2020;2:e474-e84. doi:10.1016/s2665- 9913(20)30173-9
  • Tleyjeh IM, Kashour Z, Damlaj M, et al. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis. Clin Microbiol Infect 2021;27:215-27. doi:10.1016/j.cmi.2020.10.036
  • RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 : a randomised, controlled, open-label, platform trial. Lancet 2021;397:1637- 45. doi:10.1016/s0140-6736(21)00676-0
There are 36 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Articles
Authors

Leman Delen This is me 0000-0001-9441-6979

Umut Sabri Kasapoglu This is me 0000-0003-2869-9872

Abdullah Gok This is me 0000-0002-1407-8437

Ozlem Cagasar This is me 0000-0002-6995-086X

Bora Tetık This is me 0000-0001-7696-7785

Ersoy Oksuz This is me 0000-0002-8088-1009

Publication Date October 31, 2022
Published in Issue Year 2022 Volume: 35 Issue: 3

Cite

APA Delen, L., Kasapoglu, U. S., Gok, A., Cagasar, O., et al. (2022). Efficacy of tocilizumab therapy in severe COVID-19 pneumonia patients and determination of the prognostic factors affecting 30 days mortality. Marmara Medical Journal, 35(3), 308-315. https://doi.org/10.5472/marumj.1191126
AMA Delen L, Kasapoglu US, Gok A, Cagasar O, Tetık B, Oksuz E. Efficacy of tocilizumab therapy in severe COVID-19 pneumonia patients and determination of the prognostic factors affecting 30 days mortality. Marmara Med J. October 2022;35(3):308-315. doi:10.5472/marumj.1191126
Chicago Delen, Leman, Umut Sabri Kasapoglu, Abdullah Gok, Ozlem Cagasar, Bora Tetık, and Ersoy Oksuz. “Efficacy of Tocilizumab Therapy in Severe COVID-19 Pneumonia Patients and Determination of the Prognostic Factors Affecting 30 Days Mortality”. Marmara Medical Journal 35, no. 3 (October 2022): 308-15. https://doi.org/10.5472/marumj.1191126.
EndNote Delen L, Kasapoglu US, Gok A, Cagasar O, Tetık B, Oksuz E (October 1, 2022) Efficacy of tocilizumab therapy in severe COVID-19 pneumonia patients and determination of the prognostic factors affecting 30 days mortality. Marmara Medical Journal 35 3 308–315.
IEEE L. Delen, U. S. Kasapoglu, A. Gok, O. Cagasar, B. Tetık, and E. Oksuz, “Efficacy of tocilizumab therapy in severe COVID-19 pneumonia patients and determination of the prognostic factors affecting 30 days mortality”, Marmara Med J, vol. 35, no. 3, pp. 308–315, 2022, doi: 10.5472/marumj.1191126.
ISNAD Delen, Leman et al. “Efficacy of Tocilizumab Therapy in Severe COVID-19 Pneumonia Patients and Determination of the Prognostic Factors Affecting 30 Days Mortality”. Marmara Medical Journal 35/3 (October 2022), 308-315. https://doi.org/10.5472/marumj.1191126.
JAMA Delen L, Kasapoglu US, Gok A, Cagasar O, Tetık B, Oksuz E. Efficacy of tocilizumab therapy in severe COVID-19 pneumonia patients and determination of the prognostic factors affecting 30 days mortality. Marmara Med J. 2022;35:308–315.
MLA Delen, Leman et al. “Efficacy of Tocilizumab Therapy in Severe COVID-19 Pneumonia Patients and Determination of the Prognostic Factors Affecting 30 Days Mortality”. Marmara Medical Journal, vol. 35, no. 3, 2022, pp. 308-15, doi:10.5472/marumj.1191126.
Vancouver Delen L, Kasapoglu US, Gok A, Cagasar O, Tetık B, Oksuz E. Efficacy of tocilizumab therapy in severe COVID-19 pneumonia patients and determination of the prognostic factors affecting 30 days mortality. Marmara Med J. 2022;35(3):308-15.
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