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.
Highlights
Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19
At 1 month after admission, 23/41 (56.10%) of TCZ responders and 3/10 (30%) of non-responders showed undetectable viral load (p = 0.173). In this cohort of patients admitted with COVID-19 in whom TCZ was used at an earlier stage of disease, there was a low rate of mortality
Our results support that prompt initiation of therapy with TCZ is safe in the short and mid-term, and might be associated with a favorable outcome in patients hospitalized with COVID-19, as reflected by the low overall mortality observed in our entire cohort of patients admitted for COVID-19, which was lower than the 21.8% mortality described in hospitalized patients in Spain
Summary
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. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. In contrast to other respiratory viral infections like influenza, a major pathogenic mechanism implicated in severe clinical manifestations of COVID-19 is an aberrant host immune response resulting in an excessive cytokine and chemokine release known as “cytokine storm” or “cytokine release syndrome”. Mid-term effects and incidence of disease recurrences after treatment cessation, or complications derived from the TCZ-associated immunosuppression in patients diagnosed with COVID-19 remain to be determined. The institutional guidelines included the use of TCZ at an early stage of disease, according to predefined criteria, evaluating clinical, biological and virological outcomes. In this article we describe the short and mid-term effects of early therapy with TCZ and identify predictors of a higher probability of response
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