Cardiometabolic MicroRNAs are Associated with severeerity and 28-Day Intensive Care Unit Mortality in COVID-19 Patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE176498 | GEO | 2021/11/17
REPOSITORIES: GEO
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Project description:Cardiometabolic MicroRNAs are Associated with severeerity and 28-Day Intensive Care Unit Mortality in COVID-19 Patients
| PRJNA736437 | ENA
Project description:Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia was associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). In longitudinal comparisons, COVID-19 ICU patients had a distinct proteomic trajectory associated with RNAemia and mortality. Among COVID-19-enriched proteins, galectin-3 binding protein (LGALS3BP) and proteins of the complement system were identified as interaction partners of SARS-CoV-2 spike glycoprotein. Finally, machine learning identified ‘Age, RNAemia’ and ‘Age, pentraxin-3 (PTX3)’ as the best binary signatures associated with 28-day ICU mortality.
2021-04-26 | PXD024026 | Pride
Project description:Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia was associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). In longitudinal comparisons, COVID-19 ICU patients had a distinct proteomic trajectory associated with RNAemia and mortality. Among COVID-19-enriched proteins, galectin-3 binding protein (LGALS3BP) and proteins of the complement system were identified as interaction partners of SARS-CoV-2 spike glycoprotein. Finally, machine learning identified ‘Age, RNAemia’ and ‘Age, pentraxin-3 (PTX3)’ as the best binary signatures associated with 28-day ICU mortality.
2021-04-26 | PXD024089 | Pride
Project description:Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing the host physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index and APACHE II score were poor predictors of survival. Instead, using plasma proteomes quantifying 302 plasma protein groups at 387 timepoints in 57 critically ill patients on invasive mechanical ventilation, we found 14 proteins that showed trajectories different between survivors and non-survivors. A proteomic predictor trained on single samples obtained at the first time point at maximum treatment level (i.e. WHO grade 7) and weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81, n=49). We tested the established predictor on an independent validation cohort (AUROC of 1.0, n=24). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that predictors derived from plasma protein levels have the potential to substantially outperform current prognostic markers in intensive care.
2022-03-03 | PXD029009 | Pride
Project description:The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical manifestations in disease-ridden patients. Differences in the severity of COVID-19 ranges from asymptomatic infections and mild cases to the severe form, leading to acute respiratory distress syndrome (ARDS) and multiorgan failure with poor survival. MiRNAs can regulate various cellular processes, including proliferation, apoptosis, and differentiation, by binding to the 3′UTR of target mRNAs inducing their degradation, thus serving a fundamental role in post-transcriptional repression. Alterations of miRNA levels in the blood have been described in multiple inflammatory and infectious diseases, including SARS-related coronaviruses. We used microarrays to delineate the miRNAs and snoRNAs signature in the peripheral blood of severe COVID-19 cases (n=9), as compared to mild (n=10) and asymptomatic (n=10) patients, and identified differentially expressed transcripts in severe versus asymptomatic, and others in severe versus mild COVID-19 cases. A cohort of 29 male age-matched patients were selected. All patients were previously diagnosed with COVID-19 using TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, Massachusetts), or Cobas SARS-CoV-2 Test (Roche Diagnostics, Rotkreuz, Switzerland), with a CT value < 30. Additional criterion for selection was age between 35 and 75 years. Participants were grouped into severe, mild and asymptomatic. Classifying severe cases was based on requirement of high-flow oxygen support and ICU admission (n=9). Whereas mild patients were identified based on symptoms and positive radiographic findings with pulmonary involvement (n=10). Patients with no clinical presentation were labelled as asymptomatic cases (n=10).
2022-03-01 | E-MTAB-10970 | biostudies-arrayexpress
Project description:BackgroundWe hypothesized that metabolic profiles would differ in critically ill patients with malnutrition relative to those without.Materials and methodsWe performed a prospective cohort study on 85 adult patients with systemic inflammatory response syndrome or sepsis admitted to a 20-bed medical intensive care unit (ICU) in Boston. We generated metabolomic profiles using gas and liquid chromatography and mass spectroscopy. We followed this by logistic regression and partial least squares discriminant analysis to identify individual metabolites that were significant. We then interrogated the entire metabolomics profile using metabolite set enrichment analysis and network model construction of chemical-protein target interactions to identify groups of metabolites and pathways that were differentiates in patients with and without malnutrition.ResultsOf the cohort, 38% were malnourished at admission to the ICU. Metabolomic profiles differed in critically ill patients with malnutrition relative to those without. Ten metabolites were significantly associated with malnutrition ( P < .05). A parsimonious model of 5 metabolites effectively differentiated patients with malnutrition (AUC = 0.76), including pyroglutamine and hypoxanthine. Using pathway enrichment analysis, we identified a critical role of glutathione and purine metabolism in predicting nutrition. Nutrition status was associated with 28-day mortality, even after adjustment for known phenotypic variables associated with ICU mortality. Importantly, 7 metabolites associated with nutrition status were also associated with 28-day mortality.ConclusionMalnutrition is associated with differential metabolic profiles early in critical illness. Common to all of our metabolome analyses, glutathione and purine metabolism, which play principal roles in cellular redox regulation and accelerated tissue adenosine triphosphate degradation, respectively, were significantly altered with malnutrition.
| S-EPMC8130016 | biostudies-literature
Project description:Critically ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decrease quality of life of survivors. Acute Quadriplegic Myopathy (AQM) is one of the most common neuromuscular disorders associated with ICU-acquired muscle weakness. Although there are no available treatments for the ICU-acquired muscle weakness, it has been demonstrated that early mobilization can improve its prognosis and functional outcomes. This study aims at improving our understanding of the effects of passive mechanical loading on skeletal muscle structure and function by using a unique experimental rat ICU model allowing analyses of the temporal sequence of changes in mechanically ventilated and pharmacologically paralyzed animals at durations varying from 6 h to 14 days. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle structure and function is likely a consequence of a reduced oxidative stress, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle structure and function associated with mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients. This study aims to unravel the effects of passive mechanical loading on skeletal muscle structure and function in an experimental rat ICU model at duration varying between 6h and 14 days. A total of 23 experimental female Sprague-Dawley rats were included in this study. The experimental rats were anaesthetized, treated with the neuromuscular blocking agent (NMBA) M-NM-1-cobrotoxin, mechanically ventilated and monitored for durations varying from 6h to 4 days (n=13), from 5 to 8 days (n=4), and from 9 to 14 days (n=6). The left leg of the animal was activated for 6 hours at the shortest duration and 12 hours per day at durations 12 hours and longer throughout the experiment, using a mechanical lever arm that produced a continuous passive maximal ankle joint flexions-extensions at a speed of 13.3 cycles per minute. Muscle biopsies were obtained from gastrocnemius muscle (proximal part) immediately after euthanasia, were quickly frozen in liquid propane cooled by liquid nitrogen, and stored at -80M-BM-0C. RNA was extracted.
2012-05-11 | E-GEOD-37944 | biostudies-arrayexpress
Project description:Critically ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decrease quality of life of survivors. Acute Quadriplegic Myopathy (AQM) is one of the most common neuromuscular disorders associated with ICU-acquired muscle weakness. Although there are no available treatments for the ICU-acquired muscle weakness, it has been demonstrated that early mobilization can improve its prognosis and functional outcomes. This study aims at improving our understanding of the effects of passive mechanical loading on skeletal muscle structure and function by using a unique experimental rat ICU model allowing analyses of the temporal sequence of changes in mechanically ventilated and pharmacologically paralyzed animals at durations varying from 6 h to 14 days. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle structure and function is likely a consequence of a reduced oxidative stress, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle structure and function associated with mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients.
2012-05-12 | GSE37944 | GEO
Project description:Outcomes in patients receiving invasive mechanical ventilation (IMV) are currently unclear. The present study aimed to explore the prognostic factors of the mortality rate on day 28 in patients treated in the intensive care unit (ICU) and undergoing IMV. The IMV Mortality Prediction Score (IMPRES) of 129 patients in the ICU receiving IMV after emergency (or selective) endotracheal intubation from March 2018 to August 2020 was calculated. The patients were divided into survival (n=73) and death groups (n=56) on day 28. The predictive factors of independent and combined mortality rates were determined using a receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). The AUC of the IMPRES for predicting patient death on day 28 was 0.785 (95% confidence interval (CI): 0.704-0.864, P<0.01). When the IMPRES cut-off was 4.50, the Youden index was at its maximum (0.487) with a sensitivity of 85.7% and a specificity of 63.0%. The AUC of the ventilator use time (days) at 12.5 days cut-off was 0.653 (95% CI: 0.56-0.746, P<0.01), the Youden index was 0.235 with a sensitivity of 52.1% and a specificity of 71.4%. The AUC of the IMPRES combined with the duration of ventilator use was 0.856 (95% CI: 0.789-0.922, P<0.001), the Youden index was 0.635 with a sensitivity of 84.9% and a specificity of 78.6%. The IMPRES was observed to be the main factor influencing the mortality rate of patients receiving IMV at the ICU on day 28, and the IMPRES combined with the duration of ventilator use had a significant predictive value for the 28-day mortality rates of these patients.
| S-EPMC11332165 | biostudies-literature