Preemptive interleukin-6 blockade in patients with COVID-19
Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, bu...
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Published in | Scientific reports Vol. 10; no. 1; p. 16826 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
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Nature Publishing Group UK
08.10.2020
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Abstract | Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes. |
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AbstractList | Abstract
Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes. Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes. |
ArticleNumber | 16826 |
Author | Botella, Ángela Padilla, Sergio Agulló, Vanesa Fernández, Marta García, José Alberto Masiá, Mar Guillén, Lucía García-Abellán, Javier Gutiérrez, Félix Telenti, Guillermo |
Author_xml | – sequence: 1 givenname: Lucía surname: Guillén fullname: Guillén, Lucía organization: Infectious Diseases Unit, Hospital General Universitario de Elche – sequence: 2 givenname: Sergio surname: Padilla fullname: Padilla, Sergio organization: Infectious Diseases Unit, Hospital General Universitario de Elche – sequence: 3 givenname: Marta surname: Fernández fullname: Fernández, Marta organization: Infectious Diseases Unit, Hospital General Universitario de Elche – sequence: 4 givenname: Vanesa surname: Agulló fullname: Agulló, Vanesa organization: Infectious Diseases Unit, Hospital General Universitario de Elche – sequence: 5 givenname: José Alberto surname: García fullname: García, José Alberto organization: Infectious Diseases Unit, Hospital General Universitario de Elche – sequence: 6 givenname: Guillermo surname: Telenti fullname: Telenti, Guillermo organization: Infectious Diseases Unit, Hospital General Universitario de Elche – sequence: 7 givenname: Javier surname: García-Abellán fullname: García-Abellán, Javier organization: Infectious Diseases Unit, Hospital General Universitario de Elche – sequence: 8 givenname: Ángela surname: Botella fullname: Botella, Ángela organization: Infectious Diseases Unit, Hospital General Universitario de Elche – sequence: 9 givenname: Félix surname: Gutiérrez fullname: Gutiérrez, Félix email: gutierrez_fel@gva.es organization: Clinical Medicine Department, Universidad Miguel Hernández, Universidad Miguel Hernández – sequence: 10 givenname: Mar surname: Masiá fullname: Masiá, Mar email: mmasia@umh.es organization: Clinical Medicine Department, Universidad Miguel Hernández, Universidad Miguel Hernández |
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Title | Preemptive interleukin-6 blockade in patients with COVID-19 |
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