Blockage of interleukin-1? with canakinumab in patients with Covid-19
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ABSTRACT:
SUBMITTER: Landi L
PROVIDER: S-EPMC7733468 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description: Not available
| S-BSST416 | biostudies-other
Project description:IntroductionThe fully-human monoclonal anti-interleukin (IL)-1β antibody canakinumab may inhibit the production of inflammatory mediators in patients with coronavirus disease 2019 (COVID-19) and the hyperinflammatory response potentially leading to acute respiratory distress syndrome.ObjectivesThe goal of our retrospective, observational analysis was to evaluate the safety and efficacy of subcutaneous (s.c.) canakinumab in combination with our standard of care (SOC) treatment of selected patients with COVID-19 with respiratory failure and elevated reactive pro-inflammatory markers.MethodsEight participants received two doses of s.c. canakinumab 150 mg (or 2 mg/kg for participants weighing ≤40 kg) in addition to SOC. 12 patients received only SOC treatment.ResultsCanakinumab treatment reduced the need for mechanical ventilation and reduced proinflammatory markers, resulting in an amelioration of the final outcome, with respect to the control group who received SOC alone. The treatment was safe and well tolerated; no adverse events were reported.ConclusionThe use of canakinumab (300 mg, s.c.) in the early stage of COVID-19 with mild-to-moderate respiratory failure was superior to SOC at preventing clinical deterioration and may warrant further investigation as a treatment option for patients with COVID-19 who experience a hyperinflammatory response in the early stage of the disease.
| S-EPMC8725043 | biostudies-literature
Project description: Not available
| S-BSST1269 | biostudies-other
Project description: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.
| S-EPMC7545205 | biostudies-literature
Project description: Not available
| S-BSST719 | biostudies-other
Project description:ObjectivesCanakinumab is an IL-1β antibody that neutralises the activity of IL-1β. This study examined the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia.DesignThis study aimed to evaluate the reduction in duration of hospitalisation with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study: 33 patients (cases) signed informed consent and received canakinumab (Cohort 1) and 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (Cohort 2).ResultsHospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs. 26 days, respectively; p < 0.001). There was significant clinical improvement in ventilation regimes following administration of canakinumab compared with Cohort 2 (Stuart-Maxwell test for paired data, p < 0.001). Patients treated with canakinumab experienced a significant increase in PaO2:FiO2 (p < 0.001) and reduction in lung damage by CT (p = 0.01), along with significant decreases in immune/inflammation markers that were not observed in Cohort 2. Only mild side-effects were seen in patients treated with canakinumab; survival at 60 days was 90.0% (95% CI 71.9-96.7) in patients treated with canakinumab and 73.3% (95% CI 43.6-89.1) for Cohort 2.ConclusionsTreatment with canakinumab in patients with COVID-19-related pneumonia rapidly restored normal oxygen status, decreased the need for invasive mechanical ventilation, and was associated with earlier hospital discharge and favourable prognosis versus standard of care.
| S-EPMC7771302 | biostudies-literature
Project description:Dexamethasone improves the survival of COVID-19 patients in need of supplemental oxygen therapy. Hospitalized COVID-19 patients eligible for dexamethasone therapy were recruited from the general care ward in several centers in Greece and the Netherlands and whole blood transcriptomic analysis was performed before and after starting dexamethasone treatment. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and COVID-19 patients and stimulated with inactivated SARS-CoV-2 ex vivo in the presence or absence of dexamethasone and their transcriptome was assessed.
2023-07-26 | GSE227585 | GEO
Project description:IntroductionRise of central cytokines resulting from infections produces neuronal changes. Covid-19 allows the study of depressive symptoms in sustained stress and its relationship with molecular mechanisms.ObjectivesTo assess correlation between IL-6, IL-1β and TNF-α and depressive symptoms. Characterize the depressive symptoms present.MethodsObservational study. Patients admitted for Covid-19 older than 60 years with a interleukin determination were included. The Yesavage Geriatric Depression Scale was used, associating each item with a neurotransmitter.Results27 patients included. We did not find correlation between IL-6 levels and the GDS scale score (rho = 0.204; 95% CI -0.192 to 0.543); with IL-1β levels (rho = -0.126; 95% CI -0.490 to 0.276); nor of TNF-α (rho = -0.033; 95% CI -0.416 to 0.360). 3 patients (11.1%) presented score compatible with depressive disorder. It was associated with a deficiency of Noradrenaline and Serotonin.ConclusionsWe found no correlation between the levels of IL-6, IL-1β, and TNF-α with the GDS score. Depressive symptomatology is similar to vascular depressions.
| S-EPMC7931695 | biostudies-literature
Project description:IntroductionA major contributor to coronavirus disease 2019 (COVID-19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin-38 (IL-38) is an IL-1 family member with broad anti-inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL-38 in COVID-19 patients in comparison to healthy controls, whereas two other studies report no differences in IL-38 concentrations.MethodsHere, we present an exploratory, retrospective cohort study of circulating IL-38 concentrations in hospitalized COVID-19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age- and sex-matched healthy subjects. Plasma IL-38 concentrations were measured by enzyme-linked immunosorbent assay, disease-related proteins by proximity extension assay, and clinical data were retrieved from hospital records.ResultsIL-38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL-38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL-38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL-38 and the inflammatory biomarker d-dimer was observed in men of the validation cohort. In women of the validation cohort, IL-38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL-38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL-10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein.ConclusionsThese data indicate that IL-38 is not associated with disease outcomes in hospitalized COVID-19 patients. However, moderate correlations between IL-38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL-38 concentrations are not indicative of COVID-19 severity, its anti-inflammatory effects may reduce COVID-19 severity and should be experimentally investigated.
| S-EPMC9601778 | biostudies-literature
Project description:IntroductionRise of central cytokines resulting from infections produces neuronal changes. Covid-19 allows the study of depressive symptoms in sustained stress and its relationship with molecular mechanisms.ObjectivesTo assess correlation between IL-6, IL-1β and TNF-α and depressive symptoms. Characterize the depressive symptoms present.MethodsObservational study. Patients admitted for Covid-19 older than 60 years with a interleukin determination were included. The Yesavage Geriatric Depression Scale (GDS) was used, associating each item with a neurotransmitter.Results27 patients included. We did not find correlation between IL-6 levels and the GDS scale score (rho=0.204; 95% CI -0.192 to 0.543); with IL-1β levels (rho=-0.126; 95% CI -0.490 to 0.276); nor of TNF-α (rho=-0.033; 95% CI -0.416 to 0.360). 3 patients (11.1%) presented score compatible with depressive disorder. It was associated with a deficiency of noradrenaline and serotonin.ConclusionsWe found no correlation between the levels of IL-6, IL-1β, and TNF-α with the GDS score. Depressive symptomatology is similar to vascular depressions.
| S-EPMC7837017 | biostudies-literature