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