Low-dose ruxolitinib plus steroid in severe SARS-CoV-2 pneumonia.
Ontology highlight
ABSTRACT:
SUBMITTER: D'Alessio A
PROVIDER: S-EPMC7654848 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Low-dose ruxolitinib plus steroid in severe SARS-CoV-2 pneumonia.
D'Alessio A A Del Poggio P P Bracchi F F Cesana G G Sertori N N Di Mauro D D Fargnoli A A Motta M M Giussani C C Moro P P Vitale G G Giacomini M M Borra G G
Leukemia 20201110 2
Similar Datasets
Project description:Background and methods: Ruxolitinib (RUX), a Jak1/2 inhibitor, has been reported to attenuate murine bone marrow failure recently. Its potential toxocicty of anemia and thrombocytopenia in human remains a concern. To minimize its potential toxoxicity, we tested therapeutic effectsof low dose ruxolitinib plus cyclosporine in murine model of immune-mediated bone marrow failure. Bone marrow CD8 and CD4 T cells were sorted from treated or untreated bone marrow failure mice. RNA-Seq and analysis was performed using SMART-Seq mRNA LP Kit (Takara) and the Illumina Novaseq6000, according to the Institute's protocols. Results: low dose of ruxolitinib plus cyclosporine improved pancytopenia and BM cellularity and decreased BM T cell infiltration in bone marrow failure mice. RNA sequencing demonstrated that low dose of ruxolitinib plus cyclosporine suppressed immune-related pathways in bone marrow infiltrated CD8 T cells and MHC-II expression in CD4 T cells compared with untreated mice. Conclusion: Our results demonstrate that low dose of ruxolitinib plus cyclosporine remains the efficacy in attenuation of disease and extending survival of immune-mediated bone marrow failure mice.
2024-05-08 | GSE240864 | GEO
Project description:BackgroundInterleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia.Methods53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead.FindingsOf the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%.InterpretationIL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.
| S-EPMC7531933 | biostudies-literature
Project description:BackgroundIn hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality.MethodsWe conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels.ResultsFindings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24-0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12-0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84).ConclusionIn patients with severe COVID-19 pneumonia, early administration of prolonged MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings. Clinical trial registration. ClinicalTrials.gov NCT04323592.
| S-EPMC7543560 | biostudies-literature
Project description: Not available
| S-EPMC8813567 | biostudies-literature
Project description: Not available
| S-EPMC8420430 | biostudies-literature
Project description:BackgroundCOVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed.ObjectiveTo determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19.MethodsOpen-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days.ResultsA total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients.ConclusionCsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.
| S-EPMC7753398 | biostudies-literature
Project description:IntroductionCytomegalovirus (CMV) DNAemia has been described in critically ill patients, including patients with severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection. Our objective is to evaluate the prevalence and clinical impact of CMV DNAemia among patients undergoing invasive mechanical ventilation (IMV) for severe SARS-CoV-2 infection and to explore the association between CMV DNAemia levels and clinical outcomes.MethodsIn this retrospective monocentric study, we included patients admitted in a tertiary ICU for severe COVID-19 and who required IMV. We aimed to compare clinical and demographic variables between patients with and without CMV DNAemia. Univariate and Cox regression analyses were performed to identify factors associated with CMV DNAemia.ResultsDuring the study period, CMV blood DNAemia occurred in 30/135 patients (22%). Patients with CMV blood DNAemia had longer ICU and hospital length of stay, as well as longer duration of IMV, and were more likely to have received dexamethasone. However, there was no significant difference in ICU mortality between patients with and without CMV DNAemia (64.8% vs. 56.7%, p = 0.42). The Cox regression analysis showed that dexamethasone was the only factor independently associated with CMV blood DNAemia (HR 4.23 [1.006-17.792], p = 0.049).ConclusionsIn patients with severe SARS-CoV-2 pneumonia requiring IMV, CMV DNAemia is common and associated with prolonged ventilation and increased LOS but not with increased mortality.
| S-EPMC11855763 | biostudies-literature
Project description: Not available
| S-EPMC8114591 | biostudies-literature
Project description:To test whether airway epithelial and immune cells in patients with severe SARS-CoV-2 pneumonia exhibit specific gene expression signatures (namely interferon-response signature) we have performed bronchoscopy on intubated patients with severe SARS-CoV-2 pneumonia and obtained bronchial brushings.
2021-03-05 | GSE168215 | GEO
Project description:PurposeSevere community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes.MethodsThis double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up.ResultsBetween January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications.ConclusionsIn patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.
| S-EPMC9208259 | biostudies-literature