Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
1.
Critical Care Medicine ; 51(1 Supplement):603, 2023.
Article in English | EMBASE | ID: covidwho-2190684

ABSTRACT

INTRODUCTION: Poor metabolic health increases the risk of COVID-19 acute respiratory distress syndrome (ARDS), however, its relationship with non-COVID-19 ARDS remains controversial. ARDS is often considered a heterogeneous disease caused by sepsis, pneumonia, trauma, transfusions, and aspiration. In this study, we hypothesized that metabolic inflammation may contribute to differential outcomes in ARDS primarily caused by infection. METHOD(S): This was a secondary analysis of seven studies from the ARDS and Prevention and Early Treatment of Acute Lung Injury network trials within the Biologic Specimen and Data Repository Information Coordinating Center database. A metabolic subphenotype, defined by obesity, diabetes, and hypertension, was compared to a control population. The overall results showed lower adjusted mortality with this subphenotype. In this report, we performed stratified analyses to estimate effect modification by the metabolic subphenotype. We considered metabolic inflammation to reside along the causal pathway between infection and ARDS outcomes, and as such, stratified for primary ARDS etiology (e.g., sepsis or pneumonia as compared to other primary etiologies). The primary outcome was 28-day mortality. Secondary outcomes included 90-day mortality, ventilator free days, organ-failure free days, ICU free days, and length of hospital stay. RESULT(S): Among 4,288 ARDS trial participants, 3,205 (74.7%) had primary ARDS etiologies sepsis or pneumonia and 1,083 (25.3%) aspiration, trauma, transfusions, or other causes. of those with sepsis or pneumonia, 364 (11.4%) met criteria for the subphenotype versus 2,841 (88.6%) control. In the non-infectious cohort, 90 (8.3%) met subphenotype criteria versus 993 (91.7%) control. In adjusted analyses, the subphenotype stratified by sepsis and pneumonia was associated with lower 28- and 90-day mortality (adjusted odds ratio [aOR] 0.64 [95%CI, 0.48-0.84] and aOR 0.69 [95%CI, 0.53-0.89], respectively). However, in ARDS due to other causes, analyses were not significant (mortality at 28 days, aOR 1.18 [95% CI, 0.70-1.99] and 90 days, aOR 1.26 [95% CI, 0.77-2.06]). Secondary outcomes were not significantly different. CONCLUSION(S): A metabolic subphenotype of ARDS is associated with lower risk of mortality in non-COVID ARDS primarily caused by sepsis or pneumonia.

2.
Critical Care Medicine ; 51(1 Supplement):553, 2023.
Article in English | EMBASE | ID: covidwho-2190669

ABSTRACT

INTRODUCTION: Data on obesity and diabetes in the acute respiratory distress syndrome (ARDS) are mixed. Metabolic Syndrome is a heterogeneous inflammatory state, and can be identified by metabolic risk factors. Previously, a metabolic sub-phenotype, characterized by obesity, diabetes, and hypertension, was associated with COVID-19 ARDS development and mortality. We showed this sub-phenotype was associated with lower mortality in non-COVID-19 ARDS, however, it is unclear how severity is impacted. METHOD(S): We performed a secondary analysis of individual patient-level data from seven randomized control trials in the ARDS and PETAL Networks from the Biologic Specimen and Data Repository Information Coordinating Center database. The preliminary mortality results from this study comparing the sub-phenotype to control was previously reported showing lower mortality for this sub-phenotype. Here, we studied each criterion in isolation, as an equally-weighted contributor, and also compared the outcome of severe ARDS, defined as PaO2/FiO2 ratio of less than 100 at enrollment, between cohorts. Multivariable regression models were performed. RESULT(S): Among 4,288 ARDS trial participants, 454 (10.6%) with a metabolic sub-phenotype were compared to 3,834 (89.4%) controls. Prevalence of metabolic disease was high with 2,831 (66 0%) participants carrying at least one metric of poor metabolic health (1,457-0/3 criteria, 1,398-1/3 criteria, 979-2/3 criteria, 454-3/3 criteria). The adjusted odds of dying before days 28 or 90 were progressively lower with each metabolic criterion added as compared to a nonmetabolic subgroup. Interestingly, each criterion in isolation was similarly associated with improved mortality without one particular risk factor contributing more than another, a finding supported by heterogeneity testing. Lastly, 212/454 (47%) of the metabolic sub-phenotype group met criteria for severe ARDS as compared with 1529/3834 (40%) control. The sub-phenotype was significantly associated with severe ARDS (adjusted OR 1.26 (95%CI 1.026 - 1.541). CONCLUSION(S): Obesity, diabetes, and hypertension are equal contributors to a metabolic sub-phenotype of non-COVID-19 ARDS that is significantly associated with lower mortality. However, this sub-phenotype was significantly associated with severe ARDS at enrollment.

4.
Open Respiratory Medicine Journal ; 16(1), 2022.
Article in English | Scopus | ID: covidwho-2079931

ABSTRACT

Background: Better delineation of COVID-19 presentations in different climatological conditions might assist with prompt diagnosis and isolation of patients. Objectives: To study the association of latitude and altitude with COVID-19 symptomatology. Methods: This observational cohort study included 12267 adult COVID-19 patients hospitalized between 03/2020 and 01/2021 at 181 hospitals in 24 countries within the SCCM Discovery VIRUS: COVID-19 Registry. The outcome was symptoms at admission, categorized as respiratory, gastrointestinal, neurological, mucocutaneous, cardiovascular, and constitutional. Other symptoms were grouped as atypical. Multivariable regression modeling was performed, adjusting for baseline characteristics. Models were fitted using generalized estimating equations to account for the clustering. Results: The median age was 62 years, with 57% males. The median age and percentage of patients with comorbidities increased with higher latitude. Conversely, patients with comorbidities decreased with elevated altitudes. The most common symptoms were respiratory (80%), followed by constitutional (75%). Presentation with respiratory symptoms was not associated with the location. After adjustment, at lower latitudes (<30º), patients presented less commonly with gastrointestinal symptoms (p<.001, odds ratios for 15º, 25º, and 30º: 0.32, 0.81, and 0.98, respectively). Atypical symptoms were present in 21% of the patients and showed an association with altitude (p=.026, odds ratios for 75, 125, 400, and 600 meters above sea level: 0.44, 0.60, 0.84, and 0.77, respectively). Conclusions: We observed geographic variability in symptoms of COVID-19 patients. Respiratory symptoms were most common but were not associated with the location. Gastrointestinal symptoms were less frequent in lower latitudes. Atypical symptoms were associated with higher altitude. © 2022 Tekin et al.

5.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927739

ABSTRACT

Rationale: Acute respiratory distress syndrome (ARDS) remains heterogeneous with continued difficulty discerning at-risk sub-phenotypes. Metabolic Syndrome (MetS), like ARDS, is a heterogeneous inflammatory state, commonly referred to as meta-inflammation, and is characterized by metabolic determinants of health including insulin resistance, obesity, dyslipidemia, and hypertension (HTN). Although some metabolic risk factors (e.g., obesity) are associated with ARDS, MetS has never been studied in non-COVID19 ARDS. Our objective was to determine the prevalence and risk associated with MetS among ARDS trial participants. We hypothesized MetS, identified by the clustering of obesity, HTN, and diabetes mellitus (DM), may be used to identify an ARDS sub-phenotype.Methods: An ancillary analysis of 4,708 subjects were reviewed from the ALTA, ALVEOLI, EDEN, FACTT, LaSRS, SAILS, and PETAL-ROSE trials recorded in the Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) database. MetS was classified by obesity (BMI > 30), history of diabetes, and history of hypertension or elevated blood pressure. Non-MetS patients were those without all three metabolic criteria. Cholesterol and hemoglobin A1c levels were not available and are a noted limitation. MetS prevalence, as well as each individual metabolic risk factor, was calculated across all studies. We compared 90-day mortality between patients with and without MetS as well as for each metabolic determinant of health. Complete case analysis was used to account for missing variables. Student's t-test and Pearson's chi-squared test were used for continuous and categorical variables, respectively. Multivariable logistic regression analyses included age, gender, and race, but further covariates are anticipated in future analyses.Results: Among 4,708 subjects enrolled across 7 studies, 4,406 were included in a complete dataset. There were 463 patients (9.8%) with MetS and 3,943 (89.5%) without. Prevalence of DM, HTN, and obesity were 23.8%, 42.2%, and 43.7%, respectively. Crude 90-day mortality rates were increased for subjects with DM (32.9% vs. 28.9%, p<0.05) and HTN (32.2% vs. 28.0%, p<0.01), but were decreased for subjects with obesity (27.7% vs. 31.4%, p<0.01). In adjusted analyses, 90-day mortality was significantly reduced for subjects with MetS as compared with non-MetS (adjusted odds ratio, 0.73 [95% CI 0.58-0.92], p<0.01).Conclusions: In preliminary analyses evaluating over 4,400 subjects from randomized controlled trials in ARDS, a MetS phenotype was associated with a significantly decreased risk of 90-day mortality when compared to ARDS patients without MetS. Metabolic determinants of health, in particular MetS, are understudied in critical illness and may provide insight to improve phenotyping characteristics.

6.
American Journal of Respiratory and Critical Care Medicine ; 205:1, 2022.
Article in English | English Web of Science | ID: covidwho-1880315
7.
American Journal of Respiratory and Critical Care Medicine ; 205:1, 2022.
Article in English | English Web of Science | ID: covidwho-1879978
8.
Annals of the Rheumatic Diseases ; 80(SUPPL 1):198-199, 2021.
Article in English | EMBASE | ID: covidwho-1358911

ABSTRACT

Background: Granulocyte/macrophage-colony stimulating factor (GM-CSF) is a cytokine both vital to lung homeostasis and important in regulating inflammation and autoimmunity1,2,3 that has been implicated in the pathogenesis of respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation. 4-6 Mavrilimumab is a human anti GM-CSF receptor α monoclonal antibody capable of blocking GM-CSF signaling and downregulating the inflammatory process. Objectives: To evaluate the effect of mavrilimumab on clinical outcomes in patients hospitalized with severe COVID-19 pneumonia and systemic hyperinflammation. Methods: This on-going, global, randomized, double-blind, placebo-controlled seamless transition Phase 2/3 trial was designed to evaluate the efficacy and safety of mavrilimumab in adults hospitalized with severe COVID-19 pneumonia and hyperinflammation. The Phase 2 portion comprised two groups: Cohort 1 patients requiring supplemental oxygen therapy without mechanical ventilation (to maintain SpO2 ≥92%) and Cohort 2 patients requiring mechanical ventilation, initiated ≤48 hours before randomization. Here, we report results for Phase 2, Cohort 1: 116 patients with severe COVID-19 pneumonia and hyperinflammation from USA, Brazil, Chile, Peru, and South Africa;randomized 1:1:1 to receive a single intravenous administration of mavrilimumab (10 or 6 mg/kg) or placebo. The primary efficacy endpoint was proportion of patients alive and free of mechanical ventilation at Day 29. Secondary endpoints included [1] time to 2-point clinical improvement (National Institute of Allergy and Infectious Diseases COVID-19 ordinal scale), [2] time to return to room air, and [3] mortality, all measured through Day 29. The prespecified evidentiary standard was a 2-sided α of 0.2 (not adjusted for multiplicity). Results: Baseline demographics were balanced among the intervention groups;patients were racially diverse (43% non-white), had a mean age of 57 years, and 49% were obese (BMI ≥ 30). All patients received the local standard of care: 96% received corticosteroids (including dexamethasone) and 29% received remdesivir. No differences in outcomes were observed between the 10 mg/kg and 6 mg/ kg mavrilimumab arms. Results for these groups are presented together. Mavrilimumab recipients had a reduced requirement for mechanical ventilation and improved survival: at day 29, the proportion of patients alive and free of mechanical ventilation was 12.3 percentage points higher with mavrilimumab (86.7% of patients) than placebo (74.4% of patients) (Primary endpoint;p=0.1224). Mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death through Day 29 (Hazard Ratio (HR) = 0.35;p=0.0175). Day 29 mortality was 12.5 percentage points lower in mavrilimumab recipients (8%) compared to placebo (20.5%) (p=0.0718). Mavrilimumab recipients had a 61% reduction in the risk of death through Day 29 (HR= 0.39;p=0.0726). Adverse events occurred less frequently in mavrilimumab recipients compared to placebo, including secondary infections and thrombotic events (known complications of COVID-19). Thrombotic events occurred only in the placebo arm (5/40 [12.5%]). Conclusion: In a global, diverse population of patients with severe COVID-19 pneumonia and hyperinflammation receiving supplemental oxygen therapy, corticosteroids, and remdesivir, a single infusion of mavrilimumab reduced progression to mechanical ventilation and improved survival. Results indicate mavrilimumab, a potent inhibitor of GM-CSF signaling, may have added clinical benefit on top of the current standard therapy for COVID-19. Of potential importance is that this treatment strategy is mechanistically independent of the specific virus or viral variant.

11.
Critical Care Medicine ; 49(1 SUPPL 1):51, 2021.
Article in English | EMBASE | ID: covidwho-1193819

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity and diabetes mellitus, yet a plausible mechanism remains unknown. We examined the association between hypertension, obesity, hyperlipidemia, and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak. METHODS: This was a retrospective, observational study of consecutive COVID-19 patients hospitalized at two academic tertiary hospitals in New Orleans from March 30th to April 5th, 2020. Patients were identified as MetS using WHO criteria and compared to patients without MetS. The primary outcome for all analyses was hospital mortality. Secondary outcomes included need for ICU, invasive mechanical ventilation (IMV), a diagnosis of ARDS as defined by Berlin Criteria, hospital length of stay (LOS), and hospital readmission after initial discharge. Multivariable regression models included age, sex, race, individual hospital site and Charlson Comorbidity Index as covariates. RESULTS: Among 287 patients (mean age, 61.5 years;female, 56.8%;non-Hispanic Black, 85.4%), MetS was present in 188 (66%). MetS was significantly associated with mortality (adjusted odds ratio [aOR]: 3.42, 95% confidence interval [CI]: 1.52-7.69), ICU (aOR: 4.59, CI: 2.53-8.32), IMV (aOR: 4.71, CI: 2.50-8.87) and ARDS (aOR: 4.70, CI: 2.25-9.82), compared with non-MetS. Multivariable analyses of hypertension, obesity and diabetes individually showed no association with mortality. Obesity was associated with ICU (aOR, 2.18, CI, 1.25-3.81), ARDS (aOR, 2.44, CI, 1.28-4.65), and IMV (aOR, 2.36, CI, 1.33-4.21). Diabetes was associated with ICU (aOR, 2.22, CI, 1.24-3.98) and IMV (aOR, 2.12, CI, 1.16-3.89). Hypertension was not significantly associated with any outcome. Inflammatory biomarkers associated with MetS, C-reactive protein (CRP) and lactate dehydrogenase (LDH) were associated with mortality [CRP (aOR, 3.66, CI, 1.22-10.97), LDH (aOR, 3.49, CI, 1.78-6.83)]. CONCLUSIONS: In predominantly Black patients hospitalized for COVID-19, the clustering of hypertension, obesity and diabetes as MetS increased the odds of mortality compared with non-MetS. These findings suggest that MetS may be a composite predictor of COVID-19 lethal outcome.

SELECTION OF CITATIONS
SEARCH DETAIL