Comparison of clinical outcomes of intensive care patients with COVID-19 pneumonia receiving and not receiving tocilizumab treatment

Year 2023, , 39 - 46, 20.01.2023

Hakan Dal , Esra Sultan Karabulut Keklik , Gökçe Dağtekin , Eda Yaman , Polat Pehlivanoğlu , Meltem Çimen , Süleyman Diker , Mücahit Avcil , Sema Avcı

https://doi.org/10.38053/acmj.1198167

Abstract

Aim: In patients with Coronavirus disease 2019 (COVID-19) infection, a situation called cytokine storm and an increase in proinflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 (IL-1) in the blood has been observed and it has been found that this is clinically related to the development of severe disease. Therefore, tocilizumab (TCZ) therapy that blocks IL-6 will reduce the immunological response and thus potentially harm caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study is to determine the effect of TCZ treatment on length of hospital stay, need for invasive mechanical ventilation and mortality in COVID-19 patients followed in the tertiary intensive care unit.
Material and Method: This retrospective cross-sectional study was conducted among patients hospitalized with the diagnosis of COVID-19 pneumonia between 01.09.2020 and 01.01.21 in intensive care units. Data were analyzed and evaluated separately in patients who received and did not receive TCZ treatment. Patients older than 18 years of age, who were hospitalized for at least 24 hours with the diagnosis of COVID-19 pneumonia and needed ≥36 hours of oxygen therapy, were not referred to another health center, were included in this study. Pregnant and lactating women were not included in the study. Patients with missing at least one data in the parameters to be evaluated were excluded from the study. Patients treated with an IL-6 inhibitor other than TCZ were excluded.
Results: After excluding patients who did not meet the inclusion criteria, 565 patients were included in the study. It was found that patients who received TCZ treatment after propensity score matching (PSM) had a significantly higher mean age (P<0.001) and lower obesity rates (P=0.002). There was no significant difference between the patients who received and did not receive TCZ treatment in terms of mechanical ventilation need, length of hospital stay and mortality (P=0.505, P=0.661, P=0.834).
Conclusion: As a result of our research, it was seen that TCZ treatment did not affect the need for invasive mechanical ventilation, hospital and intensive care unit stay, and mortality.

Keywords

COVID-19, pneumonia, tocilizumab, intensive care unit

References

• Zengin EN. Research trends and global productivity on mechanical ventilation with the impact of COVID-19: a bibliometric analysis in the period 1980-2021. J Health Sci Med 2022; 5: 1051-61.
• Aydemir S, Hoşgün D. The role of serum lipoprotein levels in predicting independent short-term mortality in COVID-19 patients. Anatolian Curr Med J 2022; 4: 162-6
• Uysal E, Seğmen F, Ulubaşoğlu P, Zengin EN, Erdem D. The progress of chronic renal disease patients followed by the diagnosis of COVID-19 in ICU. J Health Sci Med 2022; 5: 1447-52.
• Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. The Lancet 2020; 395: 470–3.
• Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet 2020; 395: 507-13. 
• Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 2020; 395: 497-06.
• Wu R, Wang L, Kuo HCD, et al. An update on current therapeutic drugs treating COVID-19. Current Pharmacology Reports 2020; 6: 56-70.
• 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; 55: 105954.
• Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol 2015; 16: 448-57.
• Soyöz M, Kılıçaslan Ayna T, Pirim İ. Overview of COVID-19 infection from immunological perspective. Tepecik Eğit Araşt Hast Derg 2020; 30: 101-11.
• 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.
• Republic of Turkey Ministry of Health General Directorate of Public Health. COVID-19 (SARS-CoV-2 infection) anticytokine-anti-inflammatory therapies, coagulopathy management scientific advisory board study. T.R. Ministry of Health 7 November 2020, Ankara.
• Nidadavolu LS, Walston JD. Underlying vulnerabilities to the cytokine storm and adverse COVID-19 outcomes in the aging immune system. J Gerontol A Biol Sci Med Sci 2021; 76: e13-8.
• Mo P, Xing Y, Xiao Y, et al. Clinical characteristics of refractory coronavirus disease 2019 in Wuhan, China. Clin Infect Dis 2021; 73: e4208-13.
• Du Y, Lv Y, Zha W, Zhou N, Hong X. Association of body mass index (BMI) with critical COVID-19 and in-hospital mortality: A dose-response meta-analysis. Metabolism 2021; 117: 154373.
• Palaiodimos L, Kokkinidis DG, Li W, et al. Severe obesity, increasing age and male sex are independently associated with worse in-hospital outcomes, and higher in-hospital mortality, in a cohort of patients with COVID-19 in the Bronx, New York. Metabolism 2020; 108: 154262.
• Shcherbak SG, Anisenkova AY, Mosenko SV, et al. Basic predictive risk factors for cytokine storms in COVID-19 patients. Front Immunol 2021; 12: 745515.
• Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol 2020; 2: e474-84.
• Salvarani C, Dolci G, Massari M, et al. Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. JAMA Intern Med 2021; 181: 1-9.
• Campochiaro C, Della-Torre E, Cavalli G, et al. Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study. Eur J Intern Med 2020; 76: 43-9.
• Alberdi-Iglesias A, Martín-Rodríguez F, Ortega Rabbione G, et al. Role of SpO2/FiO2 Ratio and ROX Index in Predicting Early Invasive Mechanical Ventilation in COVID-19. A Pragmatic, Retrospective, Multi-Center Study. Biomedicines 2021; 9: 1036.
• Catoire P, Tellier E, de la Rivière C, et al. Assessment of the SpO2/FiO2 ratio as a tool for hypoxemia screening in the emergency department. Am J Emerg Med 2021; 44: 116-120.
• Klopfenstein T, Zayet S, Lohse A, et al. Impact of tocilizumab on mortality and/or invasive mechanical ventilation requirement in a cohort of 206 COVID-19 patients. Int J Infect Dis 2020; 99: 491-5. 
• Salama C, Han J, Yau L, et al. Tocilizumab in Patients Hospitalized with COVID-19 Pneumonia. N Engl J Med 2021; 384: 20-30.
• Guven BB, Erturk T, Kompe Ö, Ersoy A. Serious complications in COVID-19 ARDS cases: pneumothorax, pneumomediastinum, subcutaneous emphysema and haemothorax. Epidemiol Infect 2021; 149: e137. 
• Zhou C, Gao C, Xie Y, Xu M. COVID-19 with spontaneous pneumomediastinum. Lancet Infect Dis 2020; 20: 510.
• Sun R, Liu H, Wang X. Mediastinal emphysema, giant bulla, and pneumothorax developed during the course of COVID-19 pneumonia. Korean J Radiol 2020; 21: 541-4.
• Rossotti R, Travi G, Ughi N, et al. Safety and efficacy of anti-il6-receptor tocilizumab use in severe and critical patients affected by coronavirus disease 2019: A comparative analysis. J Infect 2020; 81: e11-7.
• Martinelli AW, Ingle T, Newman J, et al. COVID-19 and pneumothorax: a multicentre retrospective case series. Eur Respir J 2020; 56: 2002697.
• Colaneri M, Bogliolo L, Valsecchi P, et al. Tocilizumab for treatment of severe COVID-19 patients: Preliminary results from SMAtteo COVID-19 Registry (SMACORE). Microorganisms 2020; 8: 695.
• Moreno-Pérez O, Andres M, Leon-Ramirez JM, et al. Experience with tocilizumab in severe COVID-19 pneumonia after 80 days of follow-up: A retrospective cohort study. J Autoimmun 2020; 114: 102523.
• Biran N, Ip A, Ahn J, et al. Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study. Lancet Rheumatol 2020; 2: e603-12.
• De Rossi N, Scarpazza C, Filippini C, et al. Early use of low dose tocilizumab in patients with COVID-19: A retrospective cohort study with a complete follow-up. EClinicalMedicine 2020; 25: 100459. 
• Rosas IO, Bräu N, Waters M, et al. Tocilizumab in Hospitalized Patients with Severe COVID-19 Pneumonia. N Engl J Med 2021; 384: 1503-16.
• Hermine O, Mariette X, Tharaux PL, et al. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA Intern Med 2021; 181: 32-40.
• 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.
• Veiga VC, Prats JAGG, Farias DLC, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ 2021; 372: n84.
• Lan SH, Lai CC, Huang HT, Chang SP, Lu LC, Hsueh PR. Tocilizumab for severe COVID-19: a systematic review and meta-analysis. Int J Antimicrob Agents 2020; 56: 106103.
• Galván-Román JM, Rodríguez-García SC, Roy-Vallejo E, et al. IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study. J Allergy Clin Immunol 2021; 147: 72-80.e8.
• Austin PC. An Introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivar Behav Res 2011; 46: 399–424.