Tocilizumab in Patients with COVID-19 Pneumonia: A Systematic Review A
Main Article Content
Abstract
Background: The use of IL-6 blocking agents has been proposed as a therapeutic option for COVID-19 pneumonia in view of the involvement of this cytokine in inflammation. Tocilizumab is the most widely evaluated IL-6 blocker within this context. In this review we looked at the evidence for safety, efficacy and outcomes of tocilizumab treatment for COVID-19 pneumonia.
Methods: A systematic search in PubMed, covering 2020 and part of 2021, yielded a sample of 19 randomized clinical trials. The present review was conducted and reported following PRISMA-IPD guidelines.
Results: The selected trials were conducted in Europe (n=6; 31.5%), Asia (n=6; 31.5%), multiple continents (n=3; 15.7%), North America (n=2; 10.5%), South America (n=1; 5.2%), and Africa (n=1; 5.2%), evaluating 7,961 adult patients, of whom 4,061 received tocilizumab and 3,630 received standard care or placebo. Tocilizumab reduced mortality in most patients (n=2985; 87.9%). Benefits were also observed with regard to hospital discharge (2 trials; one of them had a cohort of 2022 tocilizumab users, of whom 56% were benefited; the other had a cohort of 350 tocilizumab users, whom were benefited in a hazards ratio of 1.44), clinical outcomes (2 trials, with a total of 392 patients, perceived tocilizumab in a positive manner [n=350/HR=1.44 and n=42/83,3%]; 4 trials saw no benefit [n=73/39% and n=294/OR=1.26]), and the composite outcome of mechanical ventilation and death (n=2003; 32%). Patients undergoing treatment with tocilizumab and controls did not differ significantly with regard to adverse events.
Conclusion: Tocilizumab reduced the need for mechanical ventilation in hospitalized patients and improved clinical parameters. The ability of tocilizumab to reduce mortality remains uncertain. The groups displayed similar levels of adverse effects.
Keywords:
Tocilizumab, COVID-19, Pneumonia, Mechanical Ventilation, Clinical Parameters, Mortality, Outcomes
Article Details
How to Cite
VASCONCELOS, Antonio Helder Costa et al.
Tocilizumab in Patients with COVID-19 Pneumonia: A Systematic Review A.
Medical Research Archives, [S.l.], v. 13, n. 2, feb. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6220>. Date accessed: 16 mar. 2025.
doi: https://doi.org/10.18103/mra.v13i2.6220.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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4 Mishra SK, Tripathi T. One year update on the COVID-19 pandemic: Where are we now?. Acta Trop. 2021; 214:105778.
5 Ragab D, Salah EH, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol 2020; 11:1446.
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7 Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA 2020; 117:10970-75
8 Morrison AR, Johnson JM, Griebe KM, Jones MC, Stine JJ, Hencken LN, et al. Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab. J Autoimmun 2020; 114:102512.
9 Gupta S, Wang W, Hayek SS, Chan L, Mathews KS, Melamed ML, et al. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med 2021; 181: 41-51.
10 Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, 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; 181:24-31.
11 Wei Q, Lin H, Wei RG, Chen N, He F, Zou DH, et al. Tocilizumab treatment for COVID-19 patients: a systematic review and meta-analysis. Infect Dis Poverty 2021;10:71.
12 Kyriakopoulos C, Ntritsos G, Gogali A, Milionis H, Evangelou E, Kostikas K. Tocilizumab administration for the treatment of hospitalized patients with COVID-19: A systematic review and meta-analysis. Respirology 2021; 26:1027-1040.
13 Peng J, Fu M, Mei H, Zheng H, Liang G, She X, et al. Efficacy and secondary infection risk of tocilizumab, sarilumab and anakinra in COVID-19 patients: A systematic review and meta-analysis. Rev Med Virol 2022;32:e2295.
14 Lim PC, Wong KL, Rajah R, Chong MF, Chow TS, Subramaniam S, et al. Comparing the efficacy of tocilizumab with corticosteroid therapy in treating COVID-19 patients: a systematic review and meta-analysis. Daru 2022;30:211-228.
15 Klopfenstein T, Gendrin V, Gerazime A, Conrozier T, Balblanc JC, Royer PY, et al. Systematic Review and Subgroup Meta-analysis of Randomized Trials to Determine Tocilizumab's Place in COVID-19 Pneumonia. Infect Dis Ther. 2021;10:1195-1213.
16 Mahroum N, Watad A, Bridgewood C, Mansour M, Nasr A, Hussein A, et al..Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic. Int J Environ Res Public Health. 2021;18:9149.
17 Viswanatha GL, Anjana Male CKVLSN, Shylaja H. Efficacy and safety of tocilizumab in the management of COVID-19: a systematic review and meta-analysis of observational studies. Clin Exp Rheumatol 2022;40:634-646.
18 Vela D, Vela-Gaxha Z, Rexhepi M, Olloni R, Hyseni V, Nallbani R. Efficacy and safety of tocilizumab versus standard care/placebo in patients with COVID-19; a systematic review and meta-analysis of randomized clinical trials. Br J Clin Pharmacol 2022;88:1955-1963.
19 Maraolo AE, Crispo A, Piezzo M, Di Gennaro P, Vitale MG, Mallardo D, et al. The Use of Tocilizumab in Patients with COVID-19: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Studies. Review J Clin Med 2021;10:4935.
20 RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med 2021; 384:8.
21 Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med. 2021;384:795-807.
22 Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. International Journal Surgery.2021; 88:105906.
23 RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397:10285.
24 REMAP-CAP Investigators. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021; 384:16.
25 Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia. N Engl J Med. 2021; 384:16.
26 Veiga VC, Prats JAGG, Farias DLC, Rosa RG, Dourado LK, Zampieri FG, 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; 372:84.
27 Malekzadeh R, Abedini A, Mohsenpour B, Sharifipour E, Ghasemian R, Javad-Mousavi SA, et al. Subcutaneous tocilizumab in adults with severe and critical COVID-19: A prospective open-label uncontrolled multicenter trial. Int Immunopharmacol 2020; 89:107102.
28 Dastan F, Saffaei A, Haseli S, Marjani M, Moniri A, Abtahian Z, et al. Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial. Int Immunopharmacol 2020; 88:106869.
29 Ramiro S, Mostard RLM, Magro-Checa C,Van Dongen CMP, Dormans T, Buijs J, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Ann Rheum Dis 2020;79:1143-1151
30 Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS,et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020; 383:2333-2344
31 Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P, 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
32 Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021; 384:20-30.
33 Della-Torre E, Lanzillotta M, Campochiaro C, Cavalli G, De Luca G, Tomelleri A, et al. Respiratory Impairment Predicts Response to IL-1 and IL-6 Blockade in COVID-19 Patients With Severe Pneumonia and Hyper-Inflammation. Front Immunol 2021; 12:675678.
34 Strohbehn GW, Heiss BL, Rouhani SJ,Trujillo JA, Yu J, Kacew AJ, et al. COVIDOSE: A Phase II Clinical Trial of Low-Dose Tocilizumab in the Treatment of Noncritical COVID-19 Pneumonia. Clin Pharmacol Ther 2021;109:688-696.
35 Perrone F, Piccirillo MC, Ascierto PA, Salvarani C, Parrella R, Marata AM, et al. Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial. J Transl Med . 2020;18:405.
36 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; 8:420-422
37 Cantini F, Goletti D, Petrone L, Najafi Fard S, Niccoli L, Foti R. Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review. Drugs 2020; 80:1929-1946
38 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical characteristics of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395:497-506
39 Buonaguro FM, Puzanov I, Ascierto PA. Anti-IL6R role in treatment of COVID-19-related ARDS. J Transl Med 2020; 18:165.
40 Udomsinprasert W, Jittikoon J, Sangroongruangsri S, Chaikledkaew U. Circulating Levels of Interleukin-6 and Interleukin-10, But Not Tumor Necrosis Factor-Alpha, as Potential Biomarkers of Severity and Mortality for COVID-19: Systematic Review with Meta-analysis. J Clin Immunol. 2021; 41:11-22
41 Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Human Vaccines & Immunotherapeutics. 2017; 13:9.
42 Tleyjeh IM, Kashour Z, Damlaj M, Riaz M, Tlayjeh H, Altannir M, et al. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis. Clin Microbiol Infect 2021; 27:215-227
43 McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev 2020; 19:102537.
44 Soin AS, Kumar K, Choudhary NS, Sharma P, Mehta Y, Kataria S, et al. Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Respir Med. 2021; 9:511-521.
45 Peng J, Fu M, Mei H, Zheng H, Liang G, She X, et al. Efficacy and secondary infection risk of tocilizumab, sarilumab and anakinra in COVID‐19 patients: A systematic review and meta‐analysis. Rev Med Virol. 2022;32:e2295
46 Wang D, Fu B, Peng Z, Yang D, Han M, Li M, et al. Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial. Front Med 2021; 15:486-494
47 Zhao H, Zhu Q, Zhang C, Li J, Wei M, Qin Y, et al. Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size. Biomed Pharmacother 2021; 133:110825.
48 Hamed DM, Belhoul KM, Al Maazmi NA, Ghayoor F, Moin M, Al Suwaidi M, et al. Intravenous methylprednisolone with or without tocilizumab in patients with severe COVID-19 pneumonia requiring oxygen support: A prospective comparison. J Infect Public Health 2021; 14:985-989
49 Rashad A, Mousa S, Nafady-Hego H, Nafady A, Elgendy H. Short term survival of critically ill COVID-19 Egyptian patients on assisted ventilation treated by either Dexamethasone or Tocilizumab. Sci Rep 2021; 11:8816.
2 Center for Systems Science and Engineering. COVID-19 Dashboard. Updated August 8, 2021. https://systems.jhu.edu [Accessed August 8, 2021]
3 Marian AJ. Current state of vaccine development and targeted therapies for COVID-19: impact of basic science discoveries. Cardiovasc Pathol. 2021;50:107278.
4 Mishra SK, Tripathi T. One year update on the COVID-19 pandemic: Where are we now?. Acta Trop. 2021; 214:105778.
5 Ragab D, Salah EH, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol 2020; 11:1446.
6 Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395:1033-1034
7 Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA 2020; 117:10970-75
8 Morrison AR, Johnson JM, Griebe KM, Jones MC, Stine JJ, Hencken LN, et al. Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab. J Autoimmun 2020; 114:102512.
9 Gupta S, Wang W, Hayek SS, Chan L, Mathews KS, Melamed ML, et al. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med 2021; 181: 41-51.
10 Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, 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; 181:24-31.
11 Wei Q, Lin H, Wei RG, Chen N, He F, Zou DH, et al. Tocilizumab treatment for COVID-19 patients: a systematic review and meta-analysis. Infect Dis Poverty 2021;10:71.
12 Kyriakopoulos C, Ntritsos G, Gogali A, Milionis H, Evangelou E, Kostikas K. Tocilizumab administration for the treatment of hospitalized patients with COVID-19: A systematic review and meta-analysis. Respirology 2021; 26:1027-1040.
13 Peng J, Fu M, Mei H, Zheng H, Liang G, She X, et al. Efficacy and secondary infection risk of tocilizumab, sarilumab and anakinra in COVID-19 patients: A systematic review and meta-analysis. Rev Med Virol 2022;32:e2295.
14 Lim PC, Wong KL, Rajah R, Chong MF, Chow TS, Subramaniam S, et al. Comparing the efficacy of tocilizumab with corticosteroid therapy in treating COVID-19 patients: a systematic review and meta-analysis. Daru 2022;30:211-228.
15 Klopfenstein T, Gendrin V, Gerazime A, Conrozier T, Balblanc JC, Royer PY, et al. Systematic Review and Subgroup Meta-analysis of Randomized Trials to Determine Tocilizumab's Place in COVID-19 Pneumonia. Infect Dis Ther. 2021;10:1195-1213.
16 Mahroum N, Watad A, Bridgewood C, Mansour M, Nasr A, Hussein A, et al..Systematic Review and Meta-Analysis of Tocilizumab Therapy versus Standard of Care in over 15,000 COVID-19 Pneumonia Patients during the First Eight Months of the Pandemic. Int J Environ Res Public Health. 2021;18:9149.
17 Viswanatha GL, Anjana Male CKVLSN, Shylaja H. Efficacy and safety of tocilizumab in the management of COVID-19: a systematic review and meta-analysis of observational studies. Clin Exp Rheumatol 2022;40:634-646.
18 Vela D, Vela-Gaxha Z, Rexhepi M, Olloni R, Hyseni V, Nallbani R. Efficacy and safety of tocilizumab versus standard care/placebo in patients with COVID-19; a systematic review and meta-analysis of randomized clinical trials. Br J Clin Pharmacol 2022;88:1955-1963.
19 Maraolo AE, Crispo A, Piezzo M, Di Gennaro P, Vitale MG, Mallardo D, et al. The Use of Tocilizumab in Patients with COVID-19: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Studies. Review J Clin Med 2021;10:4935.
20 RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med 2021; 384:8.
21 Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med. 2021;384:795-807.
22 Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. International Journal Surgery.2021; 88:105906.
23 RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397:10285.
24 REMAP-CAP Investigators. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021; 384:16.
25 Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia. N Engl J Med. 2021; 384:16.
26 Veiga VC, Prats JAGG, Farias DLC, Rosa RG, Dourado LK, Zampieri FG, 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; 372:84.
27 Malekzadeh R, Abedini A, Mohsenpour B, Sharifipour E, Ghasemian R, Javad-Mousavi SA, et al. Subcutaneous tocilizumab in adults with severe and critical COVID-19: A prospective open-label uncontrolled multicenter trial. Int Immunopharmacol 2020; 89:107102.
28 Dastan F, Saffaei A, Haseli S, Marjani M, Moniri A, Abtahian Z, et al. Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial. Int Immunopharmacol 2020; 88:106869.
29 Ramiro S, Mostard RLM, Magro-Checa C,Van Dongen CMP, Dormans T, Buijs J, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Ann Rheum Dis 2020;79:1143-1151
30 Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS,et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020; 383:2333-2344
31 Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P, 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
32 Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021; 384:20-30.
33 Della-Torre E, Lanzillotta M, Campochiaro C, Cavalli G, De Luca G, Tomelleri A, et al. Respiratory Impairment Predicts Response to IL-1 and IL-6 Blockade in COVID-19 Patients With Severe Pneumonia and Hyper-Inflammation. Front Immunol 2021; 12:675678.
34 Strohbehn GW, Heiss BL, Rouhani SJ,Trujillo JA, Yu J, Kacew AJ, et al. COVIDOSE: A Phase II Clinical Trial of Low-Dose Tocilizumab in the Treatment of Noncritical COVID-19 Pneumonia. Clin Pharmacol Ther 2021;109:688-696.
35 Perrone F, Piccirillo MC, Ascierto PA, Salvarani C, Parrella R, Marata AM, et al. Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial. J Transl Med . 2020;18:405.
36 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; 8:420-422
37 Cantini F, Goletti D, Petrone L, Najafi Fard S, Niccoli L, Foti R. Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review. Drugs 2020; 80:1929-1946
38 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical characteristics of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395:497-506
39 Buonaguro FM, Puzanov I, Ascierto PA. Anti-IL6R role in treatment of COVID-19-related ARDS. J Transl Med 2020; 18:165.
40 Udomsinprasert W, Jittikoon J, Sangroongruangsri S, Chaikledkaew U. Circulating Levels of Interleukin-6 and Interleukin-10, But Not Tumor Necrosis Factor-Alpha, as Potential Biomarkers of Severity and Mortality for COVID-19: Systematic Review with Meta-analysis. J Clin Immunol. 2021; 41:11-22
41 Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Human Vaccines & Immunotherapeutics. 2017; 13:9.
42 Tleyjeh IM, Kashour Z, Damlaj M, Riaz M, Tlayjeh H, Altannir M, et al. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis. Clin Microbiol Infect 2021; 27:215-227
43 McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev 2020; 19:102537.
44 Soin AS, Kumar K, Choudhary NS, Sharma P, Mehta Y, Kataria S, et al. Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Respir Med. 2021; 9:511-521.
45 Peng J, Fu M, Mei H, Zheng H, Liang G, She X, et al. Efficacy and secondary infection risk of tocilizumab, sarilumab and anakinra in COVID‐19 patients: A systematic review and meta‐analysis. Rev Med Virol. 2022;32:e2295
46 Wang D, Fu B, Peng Z, Yang D, Han M, Li M, et al. Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial. Front Med 2021; 15:486-494
47 Zhao H, Zhu Q, Zhang C, Li J, Wei M, Qin Y, et al. Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size. Biomed Pharmacother 2021; 133:110825.
48 Hamed DM, Belhoul KM, Al Maazmi NA, Ghayoor F, Moin M, Al Suwaidi M, et al. Intravenous methylprednisolone with or without tocilizumab in patients with severe COVID-19 pneumonia requiring oxygen support: A prospective comparison. J Infect Public Health 2021; 14:985-989
49 Rashad A, Mousa S, Nafady-Hego H, Nafady A, Elgendy H. Short term survival of critically ill COVID-19 Egyptian patients on assisted ventilation treated by either Dexamethasone or Tocilizumab. Sci Rep 2021; 11:8816.