Tocilizumab plus glucocorticoids in severe and critically COVID-19 patients. A single center experience.
Ontology highlight
ABSTRACT:
SUBMITTER: Jimenez-Britez G
PROVIDER: S-EPMC7836292 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Tocilizumab plus glucocorticoids in severe and critically COVID-19 patients. A single center experience.
Jiménez-Brítez Gustavo G Ruiz Pablo P Soler Xavier X
Medicina clinica (English ed.) 20201109 9
Similar Datasets
Project description: Not available
| S-EPMC7346781 | biostudies-literature
Project description:The SARS-CoV-2 virus responsible for the COVID-19 pandemic can result in severe or fatal disease in a subset of infected patients. While the pathogenesis of severe COVID-19 disease has yet to be fully elucidated, an overexuberant and harmful immune response to the SARS-CoV-2 virus may be a pivotal aspect of critical illness in this patient population. The inflammatory cytokine, IL-6, has been found to be consistently elevated in severely ill COVID-19 patients, prompting speculation that IL-6 is an important driver of the pathologic process. The inappropriately elevated levels of inflammatory cytokines in COVID-19 patients is similar to cytokine release syndrome (CRS) observed in cell therapy patients. We sought to describe outcomes in a series of severely ill patients with COVID-19 CRS following treatment with anti-IL-6/IL-6-Receptor (anti-IL-6/IL-6-R) therapy, including tocilizumab or siltuximab. At our academic community medical center, we formed a multi-disciplinary committee for selecting severely ill COVID-19 patients for therapy with anti-IL-6 or IL-6-R agents. Key selection criteria included evidence of hyperinflammation, most notably elevated levels of C-reactive protein (CRP) and ferritin, and an increasing oxygen requirement. By the data cutoff point, we treated 31 patients with anti-IL-6/IL-6-R agents including 12 who had already been intubated. Overall, 27 (87%) patients are alive and 24 (77%) have been discharged from the hospital. Clinical responses to anti-IL-6/IL-6-R therapy were accompanied by significant decreases in temperature, oxygen requirement, CRP, IL-6, and IL-10 levels. Based on these data, we believe anti-IL-6/IL-6-R therapy can be effective in managing early CRS related to COVID-19 disease. Further study of anti-IL-6/IL-6-R therapy alone and in combination with other classes of therapeutics is warranted and trials are underway.
| S-EPMC7467014 | biostudies-literature
Project description:Hyperinflammation in COVID-19 plays a crucial role in pathogenesis and severity; thus, many immunomodulatory agents are applied in its treatment. We aimed to identify good clinical response predictors of tocilizumab (TCZ) treatment in severe COVID-19, among clinical, laboratory, and radiological variables. We conducted a prospective, observational study with 120 patients with severe COVID-19 not improving despite dexamethasone (DEX) treatment. We used parametric and non-parametric statistics, univariate logistic regression, receiver operating characteristic (ROC) curves, and nonlinear factors tertile analysis. In total, 86 (71.7%) patients achieved the primary outcome of a good clinical response to TCZ. We identified forty-nine predictive factors with potential utility in patient selection and treatment monitoring. The strongest included time from symptom onset between 9 and 12 days, less than 70% of estimated radiological lung involvement, and lower activity of lactate dehydrogenase. Additional predictors were associated with respiratory function, vitamin D concentration, comorbidities, and inflammatory/organ damage biomarkers. Adverse events analysis proved the safety of such a regimen. Our study confirmed that using TCZ early in the hyperinflammatory phase, before severe respiratory failure development, is most beneficial. Considering the described predictive factors, employing simple and widely available laboratory, radiological, and clinical tools can optimize patient selection for immunomodulatory treatment with TCZ.
| S-EPMC10051490 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-β (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia.
| S-EPMC7404673 | biostudies-literature
Project description:ObjectivesNovel coronavirus-19 (COVID-19) has led to over 6 million fatalities globally. An estimated 75% of COVID-19 patients who require critical care admission develop acute respiratory distress syndrome (ARDS) needing invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO). Due to prolonged ventilation requirements, these patients often also require tracheostomy. We performed a review of clinical outcomes in COVID-19 patients on ECMO at a high-volume tertiary care center in Hamilton, Ontario, Canada.MethodologyWe performed a retrospective case series, including 24 adult patients diagnosed with COVID-19 who required IMV, veno-venous (ECMO), and tracheostomy. All patients were included from April to December 2021. We extracted demographic and clinical variables pertaining to the tracheostomy procedure and ECMO therapy. We performed descriptive statistical analyses. This study was approved by the Hamilton Integrated Research Ethics Board (14217-C).ResultsWe included 24 consecutive patients with COVID-19 who required tracheostomy while undergoing ECMO therapy. The mean age was 49.4 years [standard deviation (SD): 7.33], the majority of patients were male (75%), with mean body mass index of 32 (SD: 8.81). Overall mortality rate was 33.3%. Percutaneous tracheostomy was performed most frequently (83.3%) and, similar to open tracheostomy, was associated with a low rate of perioperative bleeding complications. Within surviving patients, the mean time to IMV weaning and decannulation was 60.2 (SD: 24.6) and 49.4 days (SD: 21.8), respectively.ConclusionPercutaneous tracheostomy appears to be safe in COVID-19 patients on ECMO and holding anticoagulation 24 hours prior to and after tracheostomy may limit bleeding events in these patients.
| S-EPMC10086820 | biostudies-literature
Project description:BackgroundThe role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear.MethodsA retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400-600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied.ResultsTotals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17-0.68; P=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21-0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21-0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49-3.41; P<0.001). The occurrence of secondary infection was similar between both groups.ConclusionsThe combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.
| S-EPMC7908857 | biostudies-literature
Project description:BackgroundTreatment guidelines recommend the tocilizumab use in patients with a CRP of >7.5 mg/dL. We aimed to estimate the causal effect of glucocorticoids + tocilizumab on mortality overall and after stratification for PaO2/FiO2 ratio and CRP levels.MethodsThis was an observational cohort study of patients with severe COVID-19 pneumonia. The primary endpoint was day 28 mortality. Survival analysis was conducted to estimate the conditional and average causal effect of glucocorticoids + tocilizumab vs. glucocorticoids alone using Kaplan-Meier curves and Cox regression models with a time-varying variable for the intervention. The hypothesis of the existence of effect measure modification by CRP and PaO2/FiO2 ratio was tested by including an interaction term in the model.ResultsIn total, 992 patients, median age 69 years, 72.9% males, 597 (60.2%) treated with monotherapy, and 395 (31.8%), adding tocilizumab upon respiratory deterioration, were included. At BL, the two groups differed for median values of CRP (6 vs. 7 mg/dL; p < 0.001) and PaO2/FiO2 ratio (276 vs. 235 mmHg; p < 0.001). In the unadjusted analysis, the mortality was similar in the two groups, but after adjustment for key confounders, a significant effect of glucocorticoids + tocilizumab was observed (adjusted hazard ratio (aHR) = 0.59, 95% CI: 0.38-0.90). Although the study was not powered to detect interactions (p = 0.41), there was a signal for glucocorticoids + tocilizumab to have a larger effect in subsets, especially participants with high levels of CRP at intensification.ConclusionsOur data confirm that glucocorticoids + tocilizumab vs. glucocorticoids alone confers a survival benefit only in patients with a CRP > 7.5 mg/dL prior to treatment initiation and the largest effect for a CRP > 15 mg/dL. Large randomized studies are needed to establish an exact cut-off for clinical use.
| S-EPMC9967307 | biostudies-literature
Project description: Not available
| S-EPMC7431163 | biostudies-literature
Project description: Not available
| S-EPMC7431124 | biostudies-literature
Project description:BackgroundCurrently, two effective therapeutic options for severe aortic stenosis (AS) are available, one catheter-based [transcatheter aortic valve implantation (TAVI)], the other open surgical approach [surgical aortic valve replacement (SAVR)]. The COVID-19 pandemic has limited the availability of medical procedures. The purpose of this cross-sectional study was to assess if this pandemic had any impact on the treatment strategy of severe AS in a single cardiac center.MethodsThis study involved AS patients treated in 3-month periods (February through April) over 3 consecutive years 2018, 2019 [defined as COV(-) group] and 2020 [COV(+)]. We assessed if there were any differences regarding patients' clinical profile, applied therapeutic method, procedure complexity and early clinical outcomes.ResultsIn the years 2018 through 2019, approximately 50% of AS patients were treated classically (SAVR) while in 2020 this rate dropped to 34%. The preoperative clinical characteristic of TAVI subjects was comparable irrespective of the year. Regarding SAVR, more patients in COV(+) underwent urgent and more complex procedures. More of them were found in NYHA class III or IV, and had lower left ventricular ejection fraction (LVEF) (51.9%±14.4% vs. 58.3%±8.1%; P=0.021) than in COV(-) individuals. During the pandemic, a change in applied therapeutic methods and differences in patients' clinical profile did not have an unfavorable impact on in-hospital mortality (2.0% before vs. 3.6% during pandemic) and morbidity. Of note, intubation time and in-hospital stay were significantly shorter (P<0.05) in 2020 (4.2 hours and 7.5 days) than in the previous years (7.5 hours and 9.0 days, respectively).ConclusionsThe coronavirus pandemic has changed substantially the management of severe AS. The shift into less invasive treatment method of AS patients resulted in shortening of in-hospital stay without compromise of short-term outcomes.
| S-EPMC7947507 | biostudies-literature