Preemptive interleukin-6 blockade in patients with COVID-19

• Published in: Scientific reports Vol. 10; no. 1; p. 16826
• Main Authors: Guillén, Lucía, Padilla, Sergio, Fernández, Marta, Agulló, Vanesa, García, José Alberto, Telenti, Guillermo, García-Abellán, Javier, Botella, Ángela, Gutiérrez, Félix, Masiá, Mar
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.10.2020
• Subjects: 692/699/255; 692/700; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Betacoronavirus; Biomarkers - blood; C-Reactive Protein - analysis; Coronavirus Infections - drug therapy; Coronavirus Infections - epidemiology; Coronavirus Infections - virology; COVID-19; COVID-19 Drug Treatment; Female; Follow-Up Studies; Humanities and Social Sciences; Humans; Interleukin-6 - blood; Lymphocyte Count; Lymphocytes; Male; Middle Aged; multidisciplinary; Neutrophils; Organ Dysfunction Scores; Pandemics; Pneumonia, Viral - drug therapy; Pneumonia, Viral - epidemiology; Pneumonia, Viral - virology; Receptors, Interleukin-6 - antagonists & inhibitors; SARS-CoV-2; Science; Science (multidisciplinary); Spain - epidemiology; Treatment Outcome; Spain
• DOI: 10.1038/s41598-020-74001-3
• ISSN: 2045-2322

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.