Abstract
Aim: Coronavirus disease 2019 (COVID-19) is a pandemic with potential life-threatening outcomes. The current study aims to demonstrate the effect of tocilizumab in COVID-19 related cytokine storm.
Material and Method: This retrospective cross-sectional study evaluated the patients who received tocilizumab for COVID-19 related cytokine storm between March and August 2020. Demographic, clinical, and laboratory findings were recorded. Computerized tomography (CT) scans, which were performed before tocilizumab infusion were scored. The characteristics of the patients who survived versus those who did not survive were assessed.
Results: There was a total of 137 patients, 99 (72.3%) male and 38 (27.7%) female, with a median age of 62 years. Eighty-six (62.7%) patients had severe; 51 (37.2%) patients had critical disease course. The mortality rate was 24.1%. Higher mortality rates were present among patients older than 65 years, females, and with comorbid diseases (p=0.02, p=0.031, and p=0.01, respectively). The non-survived group had higher rates of mechanical ventilation (MV) support (85.2%) and admission to the intensive care unit (58.8%) (p<0.05). CT scores were higher in patients who did not survive compared with those who survived. Old age, critical disease, MV support, extended lung opacifications were associated with mortality according to multivariate logistic regression analysis (OR CI= 0.781, p=0.029, p=0.002, p=0.018, p=0.047, respectively).
Conclusion: We consider that due to the effect of tosilizumab in inhibiting the early stages of inflammation, it can be effective in the treatment of severe COVID-19 patients, especially under 65 years old, not requiring MV, and without extended pulmonary lesions.
Keywords
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References
- Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis 2020; 34: 101623.
- Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci 2020; 117: 10970-5.
- Lu C-C, Chen M-Y, Lee W-S, Lee Y, Chang L. Potential therapeutic agents against COVID-19: What we know so far. J Chinese Med Assoc 2020; 83: 534-6.
- Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med 2020; 382: 2327-36.
- Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe covid-19. N Engl J Med 2020; 382: 1787-99.
- Cai Q, Yang M, Liu D, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering 2020; 6: 1192-8.
- Million M, Lagier J-C, Gautret P, et al. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France. Travel Med Infect Dis 2020; 35: 101738.
- Behrens EM, Koretzky GA. Review: cytokine storm syndrome: looking toward the precision medicine era. Arthritis Rheumatol 2017; 69: 1135-43.
- Keske Ş, Tekin S, Sait B, et al. Appropriate use of tocilizumab in COVID-19 infection. Int J Infect Dis 2020; 99: 338-43.
- 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.
- Republic of Turkey Ministry of Health COVID-19 (SARS CoV-2 Infection) Guideline. http://covid19.saglik.gov.tr/TR-66341/antisitokin-antiinflamatuar-tedaviler-koagulopati-yonetimi. Accessed November 2020.
- Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: Glossary of Terms for Thoracic Imaging. Radiology 2008; 246: 697-722.
- Ooi GC, Khong PL, Müller NL, et al. Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients. Radiology 2004; 230: 836-44.
- Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol 2015; 16: 448-57.
- 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.
- 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: 529-38.
- Cifaldi L, Prencipe G, Caiello I, et al. Inhibition of natural killer cell cytotoxicity by interleukin-6: Implications for the pathogenesis of macrophage activation syndrome. Arthritis Rheumatol 2015; 67: 3037-46.
- Lykens JE, Terrell CE, Zoller EE, Risma K, Jordan MB. Perforin is a critical physiologic regulator of T-cell activation. Blood. 2011; 118: 618–26.
- Ruscitti P, Berardicurti O, Iagnocco A, Giacomelli R. Cytokine storm syndrome in severe COVID-19. Autoimmun Rev 2020; 19: 102562.
- 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.
- Hu B, Zeng LP, Yang X Lou, et al. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog 2017; 13: e1006698.
- Hong KH, Choi JP, Hong SH, et al. Predictors of mortality in Middle East respiratory syndrome (MERS). Thorax 2018; 73: 286-9.
- Choi KW, Chau TN, Tsang O, et al. Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong. Ann Intern Med 2003; 139: 715-23.
- Opal SM, Girard TD, Ely EW. The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 2005; 41: S504-12.
- Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020; 8: e21.
- Wang Y, Dong C, Hu Y, et al. Temporal changes of CT findings in 90 patients with COVID-19 pneumonia: a longitudinal study. Radiology 2020; 296: E55-64.
- Devaux CA, Rolain JM, Raoult D. ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect 2020; 53: 425-35.
- Gwathmey TM, Shaltout HA, Nixon PA, et al. Gender differences in urinary ACE and ACE2 activities in adolescents. FASEB J 2008; 22: 940-6.
- Blackburn R, Zhao H, Pebody R, Hayward A, Warren-Gash C. Laboratory-confirmed respiratory infections as predictors of hospital admission for myocardial infarction and stroke: Time-series analysis of English data for 2004-2015. Clin Infect Dis 2018; 67: 8-17.
- 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.
- Gallagher PE, Ferrario CM, Tallant EA. Regulation of ACE2 in cardiac myocytes and fibroblasts. Am J Physiol Heart Circ Physiol 2008; 295: H2373-9.
- Price CC, Altice FL, Shyr Y, et al. Tocilizumab treatment for cytokine release syndrome in hospitalized patients with coronavirus disease 2019. Chest 2020; 158: 1397–408.
- Li K, Wu J, Wu F, et al. The clinical and chest CT features associated with severe and critical COVID-19 pneumonia. Invest Radiol 2020; 55: 327-31.
- 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.
- Yuan M, Yin W, Tao Z, Tan W, Hu Y. Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China. PLoS One 2020; 15: e0230548.
- Antonio GE, Wong KT, Tsui ELH, et al. Chest radiograph scores as potential prognostic indicators in severe acute respiratory syndrome (SARS). Am J Roentgenol 2005; 184: 734-41.
- Li K, Chen D, Chen S, et al. Predictors of fatality including radiographic findings in adults with COVID-19. Respir Res 2020; 21: 146.
- Russell B, Moss C, George G, et al. Associations between immune-suppressive and stimulating drugs and novel COVID-19 - A systematic review of current evidence. Ecancermedicalscience 2020; 14: 1022.
- Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: the reality and challenges. J Microbiol Immunol Infect 2020; 53: 436-43.
- Le RQ, Li L, Yuan W, et al. FDA Approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life‐threatening cytokine release syndrome. Oncologist 2018; 23: 943-7.
Abstract
Project Number
no
References
- Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis 2020; 34: 101623.
- Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci 2020; 117: 10970-5.
- Lu C-C, Chen M-Y, Lee W-S, Lee Y, Chang L. Potential therapeutic agents against COVID-19: What we know so far. J Chinese Med Assoc 2020; 83: 534-6.
- Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med 2020; 382: 2327-36.
- Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe covid-19. N Engl J Med 2020; 382: 1787-99.
- Cai Q, Yang M, Liu D, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering 2020; 6: 1192-8.
- Million M, Lagier J-C, Gautret P, et al. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France. Travel Med Infect Dis 2020; 35: 101738.
- Behrens EM, Koretzky GA. Review: cytokine storm syndrome: looking toward the precision medicine era. Arthritis Rheumatol 2017; 69: 1135-43.
- Keske Ş, Tekin S, Sait B, et al. Appropriate use of tocilizumab in COVID-19 infection. Int J Infect Dis 2020; 99: 338-43.
- 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.
- Republic of Turkey Ministry of Health COVID-19 (SARS CoV-2 Infection) Guideline. http://covid19.saglik.gov.tr/TR-66341/antisitokin-antiinflamatuar-tedaviler-koagulopati-yonetimi. Accessed November 2020.
- Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: Glossary of Terms for Thoracic Imaging. Radiology 2008; 246: 697-722.
- Ooi GC, Khong PL, Müller NL, et al. Severe acute respiratory syndrome: temporal lung changes at thin-section CT in 30 patients. Radiology 2004; 230: 836-44.
- Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol 2015; 16: 448-57.
- 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.
- 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: 529-38.
- Cifaldi L, Prencipe G, Caiello I, et al. Inhibition of natural killer cell cytotoxicity by interleukin-6: Implications for the pathogenesis of macrophage activation syndrome. Arthritis Rheumatol 2015; 67: 3037-46.
- Lykens JE, Terrell CE, Zoller EE, Risma K, Jordan MB. Perforin is a critical physiologic regulator of T-cell activation. Blood. 2011; 118: 618–26.
- Ruscitti P, Berardicurti O, Iagnocco A, Giacomelli R. Cytokine storm syndrome in severe COVID-19. Autoimmun Rev 2020; 19: 102562.
- 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.
- Hu B, Zeng LP, Yang X Lou, et al. Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog 2017; 13: e1006698.
- Hong KH, Choi JP, Hong SH, et al. Predictors of mortality in Middle East respiratory syndrome (MERS). Thorax 2018; 73: 286-9.
- Choi KW, Chau TN, Tsang O, et al. Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong. Ann Intern Med 2003; 139: 715-23.
- Opal SM, Girard TD, Ely EW. The immunopathogenesis of sepsis in elderly patients. Clin Infect Dis 2005; 41: S504-12.
- Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020; 8: e21.
- Wang Y, Dong C, Hu Y, et al. Temporal changes of CT findings in 90 patients with COVID-19 pneumonia: a longitudinal study. Radiology 2020; 296: E55-64.
- Devaux CA, Rolain JM, Raoult D. ACE2 receptor polymorphism: Susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome. J Microbiol Immunol Infect 2020; 53: 425-35.
- Gwathmey TM, Shaltout HA, Nixon PA, et al. Gender differences in urinary ACE and ACE2 activities in adolescents. FASEB J 2008; 22: 940-6.
- Blackburn R, Zhao H, Pebody R, Hayward A, Warren-Gash C. Laboratory-confirmed respiratory infections as predictors of hospital admission for myocardial infarction and stroke: Time-series analysis of English data for 2004-2015. Clin Infect Dis 2018; 67: 8-17.
- 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.
- Gallagher PE, Ferrario CM, Tallant EA. Regulation of ACE2 in cardiac myocytes and fibroblasts. Am J Physiol Heart Circ Physiol 2008; 295: H2373-9.
- Price CC, Altice FL, Shyr Y, et al. Tocilizumab treatment for cytokine release syndrome in hospitalized patients with coronavirus disease 2019. Chest 2020; 158: 1397–408.
- Li K, Wu J, Wu F, et al. The clinical and chest CT features associated with severe and critical COVID-19 pneumonia. Invest Radiol 2020; 55: 327-31.
- 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.
- Yuan M, Yin W, Tao Z, Tan W, Hu Y. Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China. PLoS One 2020; 15: e0230548.
- Antonio GE, Wong KT, Tsui ELH, et al. Chest radiograph scores as potential prognostic indicators in severe acute respiratory syndrome (SARS). Am J Roentgenol 2005; 184: 734-41.
- Li K, Chen D, Chen S, et al. Predictors of fatality including radiographic findings in adults with COVID-19. Respir Res 2020; 21: 146.
- Russell B, Moss C, George G, et al. Associations between immune-suppressive and stimulating drugs and novel COVID-19 - A systematic review of current evidence. Ecancermedicalscience 2020; 14: 1022.
- Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: the reality and challenges. J Microbiol Immunol Infect 2020; 53: 436-43.
- Le RQ, Li L, Yuan W, et al. FDA Approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life‐threatening cytokine release syndrome. Oncologist 2018; 23: 943-7.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Original Article |
| Authors | |
| Project Number | no |
| Publication Date | March 15, 2022 |
| Published in Issue | Year 2022 Volume: 5 Issue: 2 |
Cite
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Journal of Health Sciences and Medicine
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