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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Tocilizumab: From Rheumatic Diseases to COVID-19

Author(s): Alberto Raiteri, Fabio Piscaglia, Alessandro Granito and Francesco Tovoli*

Volume 27, Issue 13, 2021

Published on: 11 March, 2021

Page: [1597 - 1607] Pages: 11

DOI: 10.2174/1381612827666210311141512

Price: $65

Abstract

Tocilizumab is a humanised interleukin-6 receptor-inhibiting monoclonal antibody that is currently approved for the treatment of rheumatoid arthritis and other immune-related conditions. Recently, tocilizumab has been investigated as a possible treatment for severe coronavirus-induced disease 2019 (COVID-19). Despite the lack of direct antiviral effects, tocilizumab could reduce the immune-induced organ damage caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infection. Until recently, most reports on tocilizumab for COVID-19 included a limited number of patients, preventing an overall evaluation of its efficacy and safety for this specific condition. Therefore, we reviewed the literature regarding the physiopathological rationale of tocilizumab for COVID-19 and its outcomes. We searched the MEDLINE database with the string “(SARS-CoV-2 OR coronavirus OR COVID-19 OR MERS- cov OR SARS-cov) AND (IL-6 OR interleukin 6 OR tocilizumab)”. While the scientific rationale supporting tocilizumab for COVID-19 is solid, the evidence regarding the outcomes remains controversial. Available data and results from ongoing trials will provide useful information in the event of new COVID-19 outbreaks or future pandemics from different coronaviruses.

Keywords: Tocilizumab, COVID-19, SARS-CoV2, tocilizumab, monoclonal antibodies, interleukin-6, cytokines.

[1]
Serio I, Tovoli F. Rheumatoid arthritis: new monoclonal antibodies. Drugs Today (Barc) 2018; 54(3): 219-30.
[http://dx.doi.org/10.1358/dot.2018.54.3.2788019] [PMID: 29771256]
[2]
Flannery CR, Little CB, Hughes CE, Curtis CL, Caterson B, Jones SA. IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage. Matrix Biol 2000; 19(6): 549-53.
[http://dx.doi.org/10.1016/S0945-053X(00)00111-6] [PMID: 11068209]
[3]
Scott LJ. Tocilizumab: A review in rheumatoid arthritis. Drugs 2017; 77(17): 1865-79.
[http://dx.doi.org/10.1007/s40265-017-0829-7] [PMID: 29094311]
[4]
Genovese MC, Kremer JM, van Vollenhoven RF, et al. Transaminase levels and hepatic events during tocilizumab treatment: pooled analysis of long-term clinical trial safety data in rheumatoid arthritis. Arthritis Rheumatol 2017; 69(9): 1751-61.
[http://dx.doi.org/10.1002/art.40176] [PMID: 28597609]
[6]
European Medicines Agency. Tocilizumab (RoActemra) 20 mg/ mL concentrate solution for infusion/162 mg solution for injection in pre-filled syringe: summary of product characteristics. 2016. Available from: http://www.ema.europa.eu
[7]
Burmester GR, Rubbert-Roth A, Cantagrel A, et al. Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA). Ann Rheum Dis 2016; 75(1): 68-74.
[http://dx.doi.org/10.1136/annrheumdis-2015-207281] [PMID: 26056119]
[8]
Hong K-H, Choi J-P, Hong S-H, et al. Predictors of mortality in Middle East respiratory syndrome (MERS). Thorax 2018; 73(3): 286-9.
[http://dx.doi.org/10.1136/thoraxjnl-2016-209313] [PMID: 28724637]
[9]
Mahmud-Al-Rafat A, Majumder A, Taufiqur Rahman KM, et al. Decoding the enigma of antiviral crisis: Does one target molecule regulate all? Cytokine 2019; 115: 13-23.
[http://dx.doi.org/10.1016/j.cyto.2018.12.008] [PMID: 30616034]
[10]
Kim ES, Choe PG, Park WB, et al. Clinical progression and cytokine profiles of middle east respiratory syndrome coronavirus infection. J Korean Med Sci 2016; 31(11): 1717-25.
[http://dx.doi.org/10.3346/jkms.2016.31.11.1717] [PMID: 27709848]
[11]
Lam CWK, Chan MHM, Wong CK. Severe acute respiratory syndrome: clinical and laboratory manifestations. Clin Biochem Rev 2004; 25(2): 121-32.
[PMID: 18458712]
[12]
Sheng W-H, Chiang B-L, Chang S-C, et al. Clinical manifestations and inflammatory cytokine responses in patients with severe acute respiratory syndrome. J Formos Med Assoc 2005; 104(10): 715-23.
[PMID: 16385373]
[13]
Jiang Y, Xu J, Zhou C, et al. Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. Am J Respir Crit Care Med 2005; 171(8): 850-7.
[http://dx.doi.org/10.1164/rccm.200407-857OC] [PMID: 15657466]
[14]
Huang K-J, Su I-J, Theron M, et al. An interferon-gamma-related cytokine storm in SARS patients. J Med Virol 2005; 75(2): 185-94.
[http://dx.doi.org/10.1002/jmv.20255] [PMID: 15602737]
[15]
Zhang Y, Li J, Zhan Y, et al. Analysis of serum cytokines in patients with severe acute respiratory syndrome. Infect Immun 2004; 72(8): 4410-5.
[http://dx.doi.org/10.1128/IAI.72.8.4410-4415.2004] [PMID: 15271897]
[16]
Lee C-H, Chen R-F, Liu J-W, et al. Altered p38 mitogen-activated protein kinase expression in different leukocytes with increment of immunosuppressive mediators in patients with severe acute respiratory syndrome. J Immunol 2004; 172(12): 7841-7.
[http://dx.doi.org/10.4049/jimmunol.172.12.7841] [PMID: 15187168]
[17]
Wong CK, Lam CWK, Wu AKL, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol 2004; 136(1): 95-103.
[http://dx.doi.org/10.1111/j.1365-2249.2004.02415.x] [PMID: 15030519]
[18]
Wang C, Pang BS. [Dynamic changes and the meanings of blood cytokines in severe acute respiratory syndrome]. Zhonghua Jie He He Hu Xi Za Zhi 2003; 26(10): 586-9.
[PMID: 14633438]
[19]
Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020; 382(8): 727-33.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[20]
Hirano T, Murakami M. COVID-19: A new virus, but a familiar receptor and cytokine release syndrome. Immunity 2020; 52(5): 731-3.
[http://dx.doi.org/10.1016/j.immuni.2020.04.003] [PMID: 32325025]
[21]
Pedersen SF, Ho Y-C. SARS-CoV-2: a storm is raging. J Clin Invest 2020; 130(5): 2202-5.
[http://dx.doi.org/10.1172/JCI137647] [PMID: 32217834]
[22]
Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020; 130(5): 2620-9.
[http://dx.doi.org/10.1172/JCI137244] [PMID: 32217835]
[23]
Chen L, Liu HG, Liu W, et al. [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi 2020; 43(3): 203-8.
[PMID: 32164089]
[24]
Cai Q, Huang D, Ou P, et al. COVID-19 in a designated infectious diseases hospital outside Hubei Province, China. Allergy 2020; 75(7): 1742-52.
[http://dx.doi.org/10.1111/all.14309] [PMID: 32239761]
[25]
Guo W, Li M, Dong Y, et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev 2020; e3319: e3319.
[http://dx.doi.org/10.1002/dmrr.3319] [PMID: 32233013]
[26]
Yuan J, Zou R, Zeng L, et al. The correlation between viral clearance and biochemical outcomes of 94 COVID-19 infected discharged patients. Inflamm Res 2020; 69(6): 599-606.
[http://dx.doi.org/10.1007/s00011-020-01342-0] [PMID: 32227274]
[27]
Sun D, Li H, Lu X-X, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study. World J Pediatr 2020; 16(3): 251-9.
[http://dx.doi.org/10.1007/s12519-020-00354-4] [PMID: 32193831]
[28]
Gao Y, Li T, Han M, et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol 2020; 92(7): 791-6.
[http://dx.doi.org/10.1002/jmv.25770] [PMID: 32181911]
[29]
Ranucci M, Ballotta A, Di Dedda U, et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost 2020; 18(7): 1747-51.
[http://dx.doi.org/10.1111/jth.14854] [PMID: 32302448]
[30]
Chen X, Zhao B, Qu Y, et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clin Infect Dis 2020.
[31]
Wan S, Yi Q, Fan S, et al. Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients. Br J Haematol 2020; 189(3): 428-37.
[http://dx.doi.org/10.1111/bjh.16659] [PMID: 32297671]
[32]
Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol 2020; 146(1): 110-8.
[http://dx.doi.org/10.1016/j.jaci.2020.04.006] [PMID: 32294485]
[33]
Zhu Z, Cai T, Fan L, et al. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Int J Infect Dis 2020; 95: 332-9.
[http://dx.doi.org/10.1016/j.ijid.2020.04.041] [PMID: 32334118]
[34]
Wang F, Hou H, Luo Y, et al. The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI Insight 2020; 5(10): 137799.
[http://dx.doi.org/10.1172/jci.insight.137799] [PMID: 32324595]
[35]
Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure. Cell Host Microbe 2020; 27(6): 992-1000.e3.
[http://dx.doi.org/10.1016/j.chom.2020.04.009] [PMID: 32320677]
[36]
Yan Y, Yang Y, Wang F, et al. Clinical characteristics and outcomes of patients with severe covid-19 with diabetes. BMJ Open Diabetes Res Care 2020; 8(1): e001343.
[http://dx.doi.org/10.1136/bmjdrc-2020-001343] [PMID: 32345579]
[37]
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.
[http://dx.doi.org/10.1016/j.jcv.2020.104370] [PMID: 32344321]
[38]
Li Y, Hu Y, Yu J, Ma T. Retrospective analysis of laboratory testing in 54 patients with severe- or critical-type 2019 novel coronavirus pneumonia. Lab Invest 2020; 100(6): 794-800.
[http://dx.doi.org/10.1038/s41374-020-0431-6] [PMID: 32341519]
[39]
Lin A, He Z-B, Zhang S, Zhang J-G, Zhang X, Yan W-H. Early risk factors for the duration of SARS-CoV-2 viral positivity in COVID-19 patients. Clinical Infectious Diseases 2020; 27: ciaa490.
[40]
Zhang J, Yu M, Tong S, Liu L-Y, Tang L-V. Predictive factors for disease progression in hospitalized patients with coronavirus disease 2019 in Wuhan, China. J Clin Virol 2020; 127: 104392.
[http://dx.doi.org/10.1016/j.jcv.2020.104392] [PMID: 32361327]
[41]
Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 2020; 55: 102763.
[http://dx.doi.org/10.1016/j.ebiom.2020.102763] [PMID: 32361250]
[42]
Wang C, Pang B. National Research Project for SARS, Beijing Group. Dynamic changes and the meanings of blood cytokines in severe acute respiratory syndrome. Zhonghua Jie He He Hu Xi Za Zhi 2003; 26(10): 586-9.
[43]
Ulhaq ZS, Soraya GV. Interleukin-6 as a potential biomarker of COVID-19 progression. Médecine et Maladies Infectieuses 2020; 50(4): 382-3.
[44]
Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 2020; 58(7): 1021-8.
[http://dx.doi.org/10.1515/cclm-2020-0369] [PMID: 32286245]
[45]
Aziz M, Fatima R, Assaly R. Elevated interleukin-6 and severe COVID-19: A meta-analysis. J Med Virol 2020; 92(11): 2283-5.
[http://dx.doi.org/10.1002/jmv.25948] [PMID: 32343429]
[46]
Lagunas-Rangel FA, Chávez-Valencia V. High IL-6/IFN-γ ratio could be associated with severe disease in COVID-19 patients. J Med Virol 2020; 92(10): 1789-90.
[http://dx.doi.org/10.1002/jmv.25900] [PMID: 32297995]
[47]
Zhou Y, Han T, Chen J, et al. Clinical and autoimmune Characteristics of Severe and critical cases of COVID-19. Clin Transl Sci 2020; 13(6): 1077-86.
[http://dx.doi.org/10.1111/cts.12805] [PMID: 32315487]
[48]
Cellina M, Orsi M, Bombaci F, Sala M, Marino P, Oliva G. Favorable changes of CT findings in a patient with COVID-19 pneumonia after treatment with tocilizumab. Diagn Interv Imaging 2020; 101(5): 323-4.
[http://dx.doi.org/10.1016/j.diii.2020.03.010] [PMID: 32278585]
[49]
Michot J-M, Albiges L, Chaput N, et al. Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report. Ann Oncol 2020; 31(7): 961-4.
[http://dx.doi.org/10.1016/j.annonc.2020.03.300] [PMID: 32247642]
[50]
Zhang X, Song K, Tong F, et al. First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab. Blood Adv 2020; 4(7): 1307-10.
[http://dx.doi.org/10.1182/bloodadvances.2020001907] [PMID: 32243501]
[51]
Di Giambenedetto S, Ciccullo A, Borghetti A, et al. Off-label use of tocilizumab in patients with SARS-CoV-2 infection. J Med Virol 2020; 92(10): 1787-8.
[http://dx.doi.org/10.1002/jmv.25897] [PMID: 32297987]
[52]
De Luna G, Habibi A, Deux JF, et al. Rapid and severe Covid-19 pneumonia with severe acute chest syndrome in a sickle cell patient successfully treated with tocilizumab. Am J Hematol 2020; 95(7): 876-8.
[http://dx.doi.org/10.1002/ajh.25833] [PMID: 32282956]
[53]
Chaidos A, Katsarou A, Mustafa C, Milojkovic D, Karadimitris A. Interleukin 6-blockade treatment for severe COVID-19 in two patients with multiple myeloma. Br J Haematol 2020; 190(1): e9-e11.
[http://dx.doi.org/10.1111/bjh.16787] [PMID: 32369612]
[54]
Fontana F, Alfano G, Mori G, et al. COVID-19 pneumonia in a kidney transplant recipient successfully treated with tocilizumab and hydroxychloroquine. Am J Transplant 2020; 20(7): 1902-6.
[http://dx.doi.org/10.1111/ajt.15935] [PMID: 32324331]
[55]
Griffin DO, Jensen A, Khan M, et al. Pulmonary embolism and increased levels of d-dimer in patients with coronavirus disease. Emerg Infect Dis 2020; 26(8): 1941-3.
[http://dx.doi.org/10.3201/eid2608.201477] [PMID: 32348233]
[56]
Coyle J, Igbinomwanhia E, Sanchez-Nadales A, Danciu S, Chu C, Shah N. A recovered case of COVID-19 myocarditis and ARDS treated with corticosteroids, tocilizumab, and experimental AT-001. JACC Case Rep 2020; p. 3.
[57]
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.
[http://dx.doi.org/10.1073/pnas.2005615117] [PMID: 32350134]
[58]
Hammami MB, Garibaldi B, Shah P, et al. Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report. Am J Transplant 2020; 20(8): 2254-9.
[http://dx.doi.org/10.1111/ajt.15985] [PMID: 32359210]
[59]
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(7): 814-8.
[http://dx.doi.org/10.1002/jmv.25801] [PMID: 32253759]
[60]
Xu C-Y, Lu S-D, Ye X, et al. Combined treatment of tocilizumab and chloroquine on severe COVID-19: a case report. QJM 2020; 113(8): 569-72.
[http://dx.doi.org/10.1093/qjmed/hcaa153] [PMID: 32365207]
[61]
Sciascia S, Aprà F, Baffa A, et al. Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19. Clin Exp Rheumatol 2020; 38(3): 529-32.
[PMID: 32359035]
[62]
Sernicola A, Carnicelli G, Di Fraia M, et al. ‘Toxic erythema’ and eosinophilia associated with tocilizumab therapy in a COVID-19 patient. J Eur Acad Dermatol Venereol 2020; 34(8): e368-70.
[http://dx.doi.org/10.1111/jdv.16620] [PMID: 32386438]
[63]
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.
[http://dx.doi.org/10.1016/j.autrev.2020.102568] [PMID: 32376398]
[64]
Morena V, Milazzo L, Oreni L, et al. Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy. Eur J Intern Med 2020; 76: 36-42.
[http://dx.doi.org/10.1016/j.ejim.2020.05.011] [PMID: 32448770]
[65]
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.
[http://dx.doi.org/10.1016/j.ejim.2020.05.021] [PMID: 32482597]
[66]
Price CC, Altice FL, Shyr Y, et al. Tocilizumab treatment for cytokine release syndrome in Hospitalized COVID-19 patients. Chest 2020; 158: 1397-408.
[http://dx.doi.org/10.1016/j.chest.2020.06.006] [PMID: 32553536]
[67]
Rojas-Marte G, Khalid M, Mukhtar O, et al. Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case-controlled study. QJM 2020; 113(8): 546-50.
[http://dx.doi.org/10.1093/qjmed/hcaa206] [PMID: 32569363]
[68]
Quartuccio L, Sonaglia A, McGonagle D, et al. Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: Results from a single Italian Centre study on tocilizumab versus standard of care. J Clin Virol 2020; 129: 104444.
[http://dx.doi.org/10.1016/j.jcv.2020.104444] [PMID: 32570043]
[69]
Conrozier T, Lohse A, Balblanc J-C, et al. Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration. Clin Exp Rheumatol 2020; 38(4): 742-7.
[PMID: 32573419]
[70]
Lohse A, Klopfenstein T, Balblanc J-C, 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(9): 500-3.
[http://dx.doi.org/10.1016/j.micinf.2020.06.005] [PMID: 32574789]
[71]
Jordan SC, Zakowski P, Tran HP, et al. Compassionate Use of tocilizumab for treatment of SARS-CoV-2 pneumonia. Clin Infect Dis 2020; 71(12): 3168-73.
[http://dx.doi.org/10.1093/cid/ciaa812] [PMID: 32575124]
[72]
Sanz Herrero F, Puchades Gimeno F, Ortega García P, Ferrer Gómez C, Ocete Mochón MD, García Deltoro M. Methylprednisolone added to tocilizumab reduces mortality in SARS‐CoV‐2 pneumonia: An observational study. J Intern Med 2020. joim.13145.
[73]
Knorr JP, Colomy V, Mauriello CM, Ha S. Tocilizumab in patients with severe COVID-19: A single-center observational analysis. J Med Virol 2020. jmv.26191.
[74]
Antony SJ, Davis MA, Davis MG, et al. Early use of tocilizumab in the prevention of adult respiratory failure in SARS-CoV-2 infections and the utilization of interleukin-6 levels in the management. J Med Virol 2021; 93(1): 491-8.
[http://dx.doi.org/10.1002/jmv.26288] [PMID: 32644254]
[75]
Morrison AR, Johnson JM, Griebe KM, et al. Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab. J Autoimmun 2020; 114: 102512.
[http://dx.doi.org/10.1016/j.jaut.2020.102512] [PMID: 32646770]
[76]
Potere N, Di Nisio M, Cibelli D, et al. Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: a case-control study. Ann Rheum Dis 2021; 80(2): 1-2.
[http://dx.doi.org/10.1136/annrheumdis-2020-218243] [PMID: 32647027]
[77]
Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clinical Infectious Diseases 2020; 11: ciaa954.
[78]
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(4): e11-7.
[http://dx.doi.org/10.1016/j.jinf.2020.07.008] [PMID: 32652164]
[79]
Baker EH, Patel K, Ball J, et al. Insights from compassionate use of tocilizumab for COVID-19 to inform appropriate design of randomised controlled trials. Br J Clin Pharmacol 2021; 87(3): 1584-6.
[http://dx.doi.org/10.1111/bcp.14466] [PMID: 32656822]
[80]
Fernández-Ruiz M, López-Medrano F, Pérez-Jacoiste Asín MA, et al. Tocilizumab for the treatment of adult patients with severe COVID-19 pneumonia: A single-center cohort study. J Med Virol 2021; 93(2): 831-42.
[http://dx.doi.org/10.1002/jmv.26308] [PMID: 32672860]
[81]
Mihai C, Dobrota R, Schröder M, et al. COVID-19 in a patient with systemic sclerosis treated with tocilizumab for SSc-ILD. Ann Rheum Dis 2020; 79(5): 668-9.
[http://dx.doi.org/10.1136/annrheumdis-2020-217442] [PMID: 32241792]
[82]
Radbel J, Narayanan N, Bhatt PJ. Use of tocilizumab for COVID-19 infection-induced cytokine release syndrome: A cautionary case report. Chest 2020; 158(1): e15-9.
[http://dx.doi.org/10.1016/j.chest.2020.04.024] [PMID: 32343968]
[83]
Matoga MM, Hosseinipour MC, Aga E, et al. Hyperlipidaemia in HIV-infected patients on lopinavir/ritonavir monotherapy in resource-limited settings. Antivir Ther 2017; 22(3): 205-13.
[http://dx.doi.org/10.3851/IMP3101] [PMID: 27740537]
[84]
Montes ML, Pulido F, Barros C, et al. Lipid disorders in antiretroviral-naive patients treated with lopinavir/ritonavir-based HAART: frequency, characterization and risk factors. J Antimicrob Chemother 2005; 55(5): 800-4.
[http://dx.doi.org/10.1093/jac/dki063] [PMID: 15761071]
[85]
Antinori S, Bonazzetti C, Gubertini G, et al. Tocilizumab for cytokine storm syndrome in COVID-19 pneumonia: an increased risk for candidemia? Autoimmun Rev 2020; 19(7): 102564.
[http://dx.doi.org/10.1016/j.autrev.2020.102564] [PMID: 32376396]
[86]
Muhović D, Bojović J, Bulatović A, et al. First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19. Liver Int 2020; 40(8): 1901-5.
[http://dx.doi.org/10.1111/liv.14516] [PMID: 32478465]
[87]
Lombardy Section Italian Society Infectious And Tropical Diseases. Vademecum for the treatment of people with COVID-19. Edition 2.0, 13 March 2020. Infez Med 2020; 128(2): 143-52.
[88]
[89]
Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med 2020; 383(24): 2333-44.
[http://dx.doi.org/10.1056/NEJMoa2028836] [PMID: 33085857]
[90]
Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med 2020. Online ahead of print.
[91]
Rosas I, Bräu N, Water M, et al. Tocilizumab in hospitalized patients with COVID-19 pneumonia. medRxiv 2020.
[92]
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 2020; e206615. Online ahead of print.
[93]
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 2020; 20: e206820.
[http://dx.doi.org/10.1001/jamainternmed.2020.6820] [PMID: 33080017]
[94]
Mao R, Qiu Y, He J-S, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2020; 5(7): 667-78.
[http://dx.doi.org/10.1016/S2468-1253(20)30126-6] [PMID: 32405603]
[95]
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(2): 215-27.
[http://dx.doi.org/10.1016/j.cmi.2020.10.036] [PMID: 33161150]

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