Comprehensive investigation of RNA-sequencing dataset reveals the hub genes and molecular mechanisms of coronavirus disease 2019 acute respiratory distress syndrome.
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ABSTRACT:
SUBMITTER: Deng W
PROVIDER: S-EPMC8441671 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo characterize the incidence and characteristics of propofol-associated hypertriglyceridemia in coronavirus disease 2019 versus noncoronavirus disease 2019 acute respiratory distress syndrome.DesignSingle-center prospective, observational cohort study.SettingMedical ICU and regional infectious containment unit.PatientsPatients with acute respiratory distress syndrome admitted from April 7, 2020, to May 15, 2020, requiring continuous propofol administration.InterventionsNone.Measurements and main resultsOf 50 patients enrolled, 54% had coronavirus disease 2019 acute respiratory distress syndrome. Median Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were 35.5 (interquartile range, 30.2-41) and 8 (interquartile range, 6-9). Pao2/Fio2 ratio was 130.5 (interquartile range, 94.5-193.8). Patients with coronavirus disease 2019-associated acute respiratory distress syndrome experienced a higher rate of hypertriglyceridemia (triglyceride ≥ 500 mg/dL) than noncoronavirus disease 2019-associated acute respiratory distress syndrome (9 [33.3%] vs 1 [4.3%]; p = 0.014). Those with coronavirus disease 2019, compared with those without, received more propofol prior to becoming hypertriglyceridemic (median, 5,436.0 mg [interquartile range, 3,405.5-6,845.5 mg] vs 4,229.0 mg [interquartile range, 2,083.4-4,972.1 mg]; p = 0.027). After adjustment for propofol dose with logistic regression (odds ratio, 5.97; 95% CI, 1.16-59.57; p = 0.031) and propensity score matching (odds ratio, 8.64; 95% CI, 1.27-149.12; p = 0.025), there remained a significant difference in the development of hypertriglyceridemia between coronavirus disease 2019-associated acute respiratory distress syndrome and noncoronavirus disease 2019-associated acute respiratory distress syndrome. There was no difference between groups in time to hypertriglyceridemia (p = 0.063). Serum lipase was not different between those who did or did not develop hypertriglyceridemia (p = 0.545). No patients experienced signs or symptoms of pancreatitis.ConclusionsPatients with coronavirus disease 2019 acute respiratory distress syndrome experienced a higher rate of propofol-associated hypertriglyceridemia than noncoronavirus disease 2019 acute respiratory distress syndrome patients, even after accounting for differences in propofol administration.
| S-EPMC7746206 | biostudies-literature
Project description:Background aimsThe acute respiratory distress syndrome (ARDS) resulting from coronavirus disease 2019 (COVID-19) is associated with a massive release of inflammatory cytokines and high mortality. Mesenchymal stromal cells (MSCs) have anti-inflammatory properties and have shown activity in treating acute lung injury. Here the authors report a case series of 11 patients with COVID-19-associated ARDS (CARDS) requiring mechanical ventilation who were treated with remestemcel-L, an allogeneic MSC product, under individual patient emergency investigational new drug applications.MethodsPatients were eligible if they were mechanically ventilated for less than 72 h prior to the first infusion. Patients with pre-existing lung disease requiring supplemental oxygen or severe liver or kidney injury were excluded. Each patient received two infusions of remestemcel-L at a dose of 2 million cells/kg per infusion given 48-120 h apart.ResultsRemestemcel-L infusions were well tolerated in all 11 patients. At the end of the 28-day follow-up period, 10 (91%, 95% confidence interval [CI], 59-100%) patients were extubated, nine (82%, 95% CI, 48-97%) patients remained liberated from mechanical ventilation and were discharged from the intensive care unit and two (18%, 95 CI%, 2-52%) patients died. The median time to extubation was 10 days. Eight (73%, 95% CI, 34-100%) patients were discharged from the hospital. C-reactive protein levels significantly declined within 5 days of MSC infusion.ConclusionsThe authors demonstrate in this case series that remestemcel-L infusions to treat moderate to severe CARDS were safe and well tolerated and resulted in improved clinical outcomes.
| S-EPMC8995321 | biostudies-literature
Project description:A 67-year-old man with a prior heart failure presented with fever, cough and dyspnea for 4 days. Physical examination showed bilateral rales on the lung exam, yet no lower extremity edema. The combination of symptoms, elevated inflammatory markers, normal baseline pro-B-type natriuretic peptide, PaO2/FiO2 < 300 and positive swab suggested coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS) rather than heart failure exacerbation. We discuss the challenges in management of ARDS in COVID-19 patients that may initially mimic as acute exacerbation of heart failure.
| S-EPMC7239589 | biostudies-literature
Project description:BackgroundAcute respiratory distress syndrome (ARDS) secondary to coronavirus disease-2019 (COVID-19) is characterized by substantial heterogeneity in clinical, biochemical, and physiological characteristics. However, the pathophysiology of severe COVID-19 infection is poorly understood. Previous studies established clinical and biological phenotypes among classical ARDS cohorts, with important therapeutic implications. The phenotypic profile of COVID-19 associated ARDS remains unknown.MethodsWe used latent class modeling via a multivariate mixture model to identify phenotypes from clinical and biochemical data collected from 263 patients admitted to Massachusetts General Hospital intensive care unit with COVID-19-associated ARDS between March 13 and August 2, 2020.FindingsWe identified two distinct phenotypes of COVID-19-associated ARDS, with substantial differences in biochemical profiles despite minimal differences in respiratory dynamics. The minority phenotype (class 2, n = 70, 26·6%) demonstrated increased markers of coagulopathy, with mild relative hyper-inflammation and dramatically increased markers of end-organ dysfunction (e.g., creatinine, troponin). The odds of 28-day mortality among the class 2 phenotype was more than double that of the class 1 phenotype (40·0% vs.· 23·3%, OR = 2·2, 95% CI [1·2, 3·9]).InterpretationWe identified distinct phenotypic profiles in COVID-19 associated ARDS, with little variation according to respiratory physiology but with important variation according to systemic and extra-pulmonary markers. Phenotypic identity was highly associated with short-term mortality. The class 2 phenotype exhibited prominent signatures of coagulopathy, suggesting that vascular dysfunction may play an important role in the clinical progression of severe COVID-19-related disease.
| S-EPMC8047387 | biostudies-literature
Project description:ObjectivesDue to the rapid rate of severe acute respiratory syndrome coronavirus 2 transmission and the heterogeneity of symptoms of coronavirus disease 2019, expeditious and effective triage is critical for early treatment and effective allocation of hospital resources.DesignA post hoc analysis of respiratory data from non-invasive venous waveform analysis among patients enrolled in an observational study was performed.SettingVanderbilt University Medical Center.PatientsPeripheral venous waveforms were recorded from admission to discharge in enrolled coronavirus disease 2019-positive patients and healthy age-matched controls.InterventionsData were analyzed in LabChart 8 to transform venous waveforms to the frequency domain using fast Fourier transforms. The peak respiratory frequency was normalized to the peak cardiac frequency to generate a respiratory non-invasive venous waveform analysis respiratory index. Paired Fisher exact tests were used to compare each patient's respiratory non-invasive venous waveform analysis respiratory index at admission and discharge. A nonparametric one-way analysis of variance was used for multiple comparisons between patients with coronavirus disease 2019 and healthy controls for respiratory non-invasive venous waveform analysis respiratory index.Measurements and main resultsFifty coronavirus disease 2019-positive patients were enrolled between April 2020, and September 2020, and 45 were analyzed; 34 required supplemental oxygen and 11 did not. The respiratory non-invasive venous waveform analysis respiratory index was significantly higher for the 34 patients with coronavirus disease 2019 who received supplemental oxygen (median, 0.27; interquartile range, 0.11-1.28) compared with the 34 healthy controls (median, 0.06; interquartile range, 0.03-0.14) (p < 0.01). For patients with coronavirus disease 2019 who received supplemental oxygen, respiratory non-invasive venous waveform analysis respiratory index was significantly lower at hospital discharge (p = 0.02; 95% CI, 0.10-1.9) compared with hospital admission (median = 0.12; interquartile range, 0.05-0.56). For patients with coronavirus disease 2019, a respiratory non-invasive venous waveform analysis respiratory index of 0.64 demonstrated sensitivity of 92%, specificity of 47%, and positive predictive value of 93% for predicting requirement of supplemental oxygen during the hospitalization.ConclusionsRespiratory non-invasive venous waveform analysis respiratory index represents a novel physiologic respiratory measurement with a promising ability to triage early care and predict the need for oxygen support therapy in coronavirus disease 2019 patients.
| S-EPMC8489896 | biostudies-literature
Project description:ObjectivesTo assess whether right ventricular dilation or systolic impairment is associated with mortality and/or disease severity in invasively ventilated patients with coronavirus disease 2019 acute respiratory distress syndrome.DesignRetrospective cohort study.SettingSingle-center U.K. ICU.PatientsPatients with coronavirus disease 2019 acute respiratory distress syndrome undergoing invasive mechanical ventilation that received a transthoracic echocardiogram between March and December 2020.InterventionNone.Measurements and main resultsRight ventricular dilation was defined as right ventricular:left ventricular end-diastolic area greater than 0.6, right ventricular systolic impairment as fractional area change less than 35%, or tricuspid annular plane systolic excursion less than 17 mm. One hundred seventy-two patients were included, 59 years old (interquartile range, 49-67), with mostly moderate acute respiratory distress syndrome (n = 101; 59%). Ninety-day mortality was 41% (n = 70): 49% in patients with right ventricular dilation, 53% in right ventricular systolic impairment, and 72% in right ventricular dilation with systolic impairment. The right ventricular dilation with systolic impairment phenotype was independently associated with mortality (odds ratio, 3.11 [95% CI, 1.15-7.60]), but either disease state alone was not. Right ventricular fractional area change correlated with Pao2:Fio2 ratio, Paco2, chest radiograph opacification, and dynamic compliance, whereas right ventricular:left ventricle end-diastolic area correlated negatively with urine output.ConclusionsRight ventricular systolic impairment correlated with pulmonary pathophysiology, whereas right ventricular dilation correlated with renal dysfunction. Right ventricular dilation with systolic impairment was the only right ventricular phenotype that was independently associated with mortality.
| S-EPMC8439642 | biostudies-literature
Project description:BackgroundThe management of COVID-19 ARDS is debated. Although current evidence does not suggest an atypical acute respiratory distress syndrome (ARDS), the physiological response to prone positioning is not fully understood and it is unclear which patients benefit. We aimed to determine whether proning increases oxygenation and to evaluate responders.MethodsThis case series from a single, tertiary university hospital includes all mechanically ventilated patients with COVID-19 and proning between 17 March 2020 and 19 May 2020. The primary measure was change in PaO2 :FiO2 .ResultsForty-four patients, 32 males/12 females, were treated with proning for a total of 138 sessions, with median (range) two (1-8) sessions. Median (IQR) time for the five sessions was 14 (12-17) hours. In the first session, median (IQR) PaO2 :FiO2 increased from 104 (86-122) to 161 (127-207) mm Hg (P < .001). 36/44 patients (82%) improved in PaO2 :FiO2 , with a significant increase in PaO2 :FiO2 in the first three sessions. Median (IQR) FiO2 decreased from 0.7 (0.6-0.8) to 0.5 (0.35-0.6) (<0.001). A significant decrease occurred in the first three sessions. PaO2 , tidal volumes, PEEP, mean arterial pressure (MAP), and norepinephrine infusion did not differ. Primarily, patients with PaO2 :FiO2 approximately < 120 mm Hg before treatment responded to proning. Age, sex, BMI, or SAPS 3 did not predict success in increasing PaO2 :FiO2 .ConclusionProning increased PaO2 :FiO2 , primarily in patients with PaO2 :FiO2 approximately < 120 mm Hg, with a consistency over three sessions. No characteristic was associated with non-responding, why proning may be considered in most patients. Further study is required to evaluate mortality.
| S-EPMC7894343 | biostudies-literature
Project description:ObjectivesMicrovascular thrombosis contributes to acute respiratory distress syndrome pathophysiology and has been demonstrated in coronavirus disease 2019-associated acute respiratory distress syndrome. Clinical laboratory measurements of coagulation and disseminated intravascular coagulation, such as coagulation factor function, platelet count, and fibrinogen, may not fully reflect the extent of microvascular thrombosis present in these patients. We investigated thromboelastography in patients with coronavirus disease 2019-associated acute respiratory distress syndrome with the objective of characterizing suspected coagulopathy and impaired fibrinolysis.DesignRetrospective observational cohort study.SettingSingle-center academic medical center.PatientsTen patients with polymerase chain reaction-confirmed coronavirus disease 2019 disease complicated by acute respiratory distress syndrome.InterventionsMeasurement of thromboelastography (n = 10) and thrombolysis with alteplase (n = 4).Measurements and main resultsHypercoagulability and decreased or absent fibrinolysis were demonstrated by thromboelastography. Thrombocytopenia and hypofibrinogenemia were not observed, while seven of 10 patients had elevated d-dimer values. For patients who received thrombolytic therapy, repeat thromboelastography demonstrated improvements in coagulation index and lysis at 30 minutes reflecting reduced hypercoagulability and increased fibrinolysis. One major bleeding complication was detected following thrombolysis. Eight of 10 patients survived and were successfully extubated, and six of 10 have since been discharged.ConclusionsIn coronavirus disease 2019 patients with acute respiratory distress syndrome in whom thromboelastography was performed, hypercoagulability and impaired fibrinolysis were observed. In the context of autopsy studies demonstrating pulmonary microvascular thromboses in coronavirus disease 2019 patients, noninvasive detection of hypercoagulability and deficient fibrinolysis in coronavirus disease 2019 acute respiratory distress syndrome using thromboelastography could improve understanding and management of coronavirus disease 2019.
| S-EPMC7498137 | biostudies-literature
Project description:Vascular injury is a well-established, disease-modifying factor in acute respiratory distress syndrome (ARDS) pathogenesis. Recently, coronavirus disease 2019 (COVID-19)-induced injury to the vascular compartment has been linked to complement activation, microvascular thrombosis, and dysregulated immune responses. This study sought to assess whether aberrant vascular activation in this prothrombotic context was associated with the induction of necroptotic vascular cell death. To achieve this, proteomic analysis was performed on blood samples from COVID-19 subjects at distinct time points during ARDS pathogenesis (hospitalized at risk, N = 59; ARDS, N = 31; and recovery, N = 12). Assessment of circulating vascular markers in the at-risk cohort revealed a signature of low vascular protein abundance that tracked with low platelet levels and increased mortality. This signature was replicated in the ARDS cohort and correlated with increased plasma angiopoietin 2 levels. COVID-19 ARDS lung autopsy immunostaining confirmed a link between vascular injury (angiopoietin 2) and platelet-rich microthrombi (CD61) and induction of necrotic cell death [phosphorylated mixed lineage kinase domain-like (pMLKL)]. Among recovery subjects, the vascular signature identified patients with poor functional outcomes. Taken together, this vascular injury signature was associated with low platelet levels and increased mortality and can be used to identify ARDS patients most likely to benefit from vascular targeted therapies.
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Project description:Hypoxemia and hypercarbia resulting from a lack of surfactant is considered to be the primary mechanism underlying neonatal respiratory distress syndrome (NRDS). Surfactant replacement therapy may mitigate the symptoms of the disease by decreasing the surface tension of alveoli and facilitating inflation. However, surfactant serves an additional role in immunological processes. Therefore, it may be hypothesized that mechanisms of NRDS involving surfactant exert additional functions to promoting alveolar inflation. Using peripheral blood obtained from mature infants with and without NRDS, in tandem with mRNA sequencing (mRNA‑seq) analysis, the present study identified that, while cell cycle regulation and alveolar surfactants serve a role in deterring the further onset of NRDS, innate and pathogen‑induced responses of the immune system are among the most important factors in the pathology. The present study illustrated the regulatory importance of these immune pathways in response to alterations in the expression of gene families, particularly in perpetual lung injury leading to NRDS. Notably, data collected from the mRNA‑seq analysis revealed similar mechanisms between NRDS and acute respiratory distress syndrome, a clinical phenotype precipitated by the manifestation of a severe form of lung injury due to numerous lung insults, implying that similar therapies may be applied to treat these two diseases.
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