Project description:BackgroundThe correlates of COVID-19 illness severity following infection with SARS-Coronavirus 2 (SARS-CoV-2) are incompletely understood.MethodsWe assessed peripheral blood gene expression in 53 adults with confirmed SARS-CoV-2-infection clinically adjudicated as having mild, moderate or severe disease. Supervised principal components analysis was used to build a weighted gene expression risk score (WGERS) to discriminate between severe and non-severe COVID.ResultsGene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus non-severe illness, we identified >4000 genes differentially expressed (FDR<0.05). Biological pathways increased in severe COVID-19 were associated with platelet activation and coagulation, and those significantly decreased with T cell signaling and differentiation. A WGERS based on 18 genes distinguished severe illness in our training cohort (cross-validated ROC-AUC=0.98), and need for intensive care in an independent cohort (ROC-AUC=0.85). Dichotomizing the WGERS yielded 100% sensitivity and 85% specificity for classifying severe illness in our training cohort, and 84% sensitivity and 74% specificity for defining the need for intensive care in the validation cohort.ConclusionThese data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity.
Project description:The correlates of COVID-19 illness severity following infection with SARS-Coronavirus 2 (SARS-CoV-2) are incompletely understood. We assessed peripheral blood gene expression in 53 adults with confirmed SARS-CoV-2-infection clinically adjudicated as having mild, moderate or severe disease. Supervised principal components analysis was used to build a weighted gene expression risk score (WGERS) to discriminate between severe and non-severe COVID. Gene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus non-severe illness, we identified >4000 genes differentially expressed (FDR<0.05). Biological pathways increased in severe COVID-19 were associated with platelet activation and coagulation, and those significantly decreased with T cell signaling and differentiation. A WGERS based on 18 genes distinguished severe illness in our training cohort (cross-validated ROC-AUC=0.98), and need for intensive care in an independent cohort (ROC-AUC=0.85). Dichotomizing the WGERS yielded 100% sensitivity and 85% specificity for classifying severe illness in our training cohort, and 84% sensitivity and 74% specificity for defining the need for intensive care in the validation cohort. These data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity.
Project description:The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges in critical care medicine, including extreme demand for intensive care unit (ICU) resources and rapidly evolving understanding of a novel disease. Up to one-third of hospitalized patients with COVID-19 experience critical illness. The most common form of organ failure in COVID-19 critical illness is acute hypoxemic respiratory failure, which clinically presents as acute respiratory distress syndrome (ARDS) in three-quarters of ICU patients. Noninvasive respiratory support modalities are being used with increasing frequency given their potential to reduce the need for intubation. Determining optimal patient selection for and timing of intubation remains a challenge. Management of mechanically ventilated patients with COVID-19 largely mirrors that of non-COVID-19 ARDS. Organ failure is common and portends a poor prognosis. Mortality rates have improved over the course of the pandemic, likely owing to increasing disease familiarity, data-driven pharmacologics, and improved adherence to evidence-based critical care.
Project description:ObjectiveRecent cohort studies have identified obesity as a risk factor for poor outcomes in coronavirus disease 2019 (COVID-19). To further explore the relationship between obesity and critical illness in COVID-19, the association of BMI with baseline demographic and intensive care unit (ICU) parameters, laboratory values, and outcomes in a critically ill patient cohort was examined.MethodsIn this retrospective study, the first 277 consecutive patients admitted to Massachusetts General Hospital ICUs with laboratory-confirmed COVID-19 were examined. BMI class, initial ICU laboratory values, physiologic characteristics including gas exchange and ventilatory mechanics, and ICU interventions as clinically available were measured. Mortality, length of ICU admission, and duration of mechanical ventilation were also measured.ResultsThere was no difference found in respiratory system compliance or oxygenation between patients with and without obesity. Patients without obesity had higher initial ferritin and D-dimer levels than patients with obesity. Standard acute respiratory distress syndrome management, including prone ventilation, was equally distributed between BMI groups. There was no difference found in outcomes between BMI groups, including 30- and 60-day mortality and duration of mechanical ventilation.ConclusionsIn this cohort of critically ill patients with COVID-19, obesity was not associated with meaningful differences in respiratory physiology, inflammatory profile, or clinical outcomes.
Project description:To examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE).An international study evaluated newly diagnosed SLE patients for neuropsychiatric events attributed to SLE and non-SLE causes. The outcome of events was determined by a physician-completed seven-point scale and compared with patient-completed Short Form 36 (SF-36) health survey questionnaires. Statistical analysis used linear mixed-effects regression models with patient-specific random effects.274 patients (92% female; 68% Caucasian), from a cohort of 1400, had one or more neuropsychiatric event in which the interval between assessments was 12.3 ± 2 months. The overall difference in change between visits in mental component summary (MCS) scores of the SF-36 was significant (p<0.0001) following adjustments for gender, ethnicity, centre and previous score. A consistent improvement in neuropsychiatric status (N=295) was associated with an increase in the mean (SD) adjusted MCS score of 3.66 (0.89) in SF-36 scores. Between paired visits when the neuropsychiatric status consistently deteriorated (N=30), the adjusted MCS score decreased by 4.00 (1.96). For the physical component summary scores the corresponding changes were +1.73 (0.71) and -0.62 (1.58) (p<0.05), respectively. Changes in SF-36 subscales were in the same direction (p<0.05; with the exception of role physical). Sensitivity analyses confirmed these findings. Adjustment for age, education, medications, SLE disease activity, organ damage, disease duration, attribution and characteristics of neuropsychiatric events did not substantially alter the results.Changes in SF-36 summary and subscale scores, in particular those related to mental health, are strongly associated with the clinical outcome of neuropsychiatric events in SLE patients.
Project description:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a rare disease with a median survival of 3-5?years after diagnosis with limited treatment options. The aim of this study is to assess the psychometric characteristics of the Short Form 36 Health Status Questionnaire (SF-36) in IPF and to provide disease specific minimally important differences (MID). METHODS:Data source was the European IPF Registry (eurIPFreg). The psychometric properties of the SF-36 version 2 were evaluated based on objective clinical measures as well as subjective perception. We analysed acceptance, feasibility, discrimination ability, construct and criterion validity, responsiveness and test-retest-reliability. MIDs were estimated via distribution and anchor-based approaches. RESULTS:The study population included 258 individuals (73.3% male; mean age 67.3?years, SD 10.7). Of them 75.2% (194 individuals) had no missing item. The distribution of several items was skewed, although floor effect was acceptable. Physical component score (PCS) correlated significantly and moderately with several anchors, whereas the correlations of mental component score (MCS) and anchors were only small. The tests showed mainly significant lower HRQL in individuals with long-term oxygen therapy. Analyses in stable individuals did not show significant changes of HRQL except for one dimension and anchor. Individuals with relevant changes of the health status based on the anchors had significant changes in all SF-36 dimensions and summary scales except for the dimension PAIN. PCS and MCS had mean MIDs of five and six, respectively. Mean MIDs of the dimensions ranged from seven to 21. CONCLUSION:It seems that the SF-36 is a valid instrument to measure HRQL in IPF and so can be used in RCTs or individual monitoring of disease. Nevertheless, the additional evaluation of longitudinal aspects and MIDs can be recommended to further analyse these factors. Our findings have a great potential impact on the evaluation of IPF patients. TRIAL REGISTRATION:The eurIPFreg and eurIPFbank are listed in https://clinicaltrials.gov ( NCT02951416 ).
Project description:OBJECTIVES:A simple evaluation tool for patients with novel coronavirus disease 2019 (COVID-19) could assist the physicians to triage COVID-19 patients effectively and rapidly. This study aimed to evaluate the predictive value of 5 early warning scores based on the admission data of critical COVID-19 patients. METHODS:Overall, medical records of 319 COVID-19 patients were included in the study. Demographic and clinical characteristics on admission were used for calculating the Standardized Early Warning Score (SEWS), National Early Warning Score (NEWS), National Early Warning Score2 (NEWS2), Hamilton Early Warning Score (HEWS), and Modified Early Warning Score (MEWS). Data on the outcomes (survival or death) were collected for each case and extracted for overall and subgroup analysis. Receiver operating characteristic curve analyses were performed. RESULTS:The area under the receiver operating characteristic curve for the SEWS, NEWS, NEWS2, HEWS, and MEWS in predicting mortality were 0.841 (95% CI: 0.765-0.916), 0.809 (95% CI: 0.727-0.891), 0.809 (95% CI: 0.727-0.891), 0.821 (95% CI: 0.748-0.895), and 0.670 (95% CI: 0.573-0.767), respectively. CONCLUSIONS:SEWS, NEWS, NEWS2, and HEWS demonstrated moderate discriminatory power and, therefore, offer potential utility as prognostic tools for screening severely ill COVID-19 patients. However, MEWS is not a good prognostic predictor for COVID-19.
Project description:RationaleHealth-related quality of life (HRQL) is an important outcome in drug trials. Little is known about how the Short Form-36 (SF-36) and Saint George's Respiratory Questionnaire (SGRQ) perform in idiopathic pulmonary fibrosis (IPF).ObjectivesTo examine the validity of the SF-36 and SGRQ and to determine scores from each that would constitute a minimum important difference (MID).MethodsWe analyzed data from a recently completed trial that enrolled subjects with well-defined IPF who completed the SF-36, SGRQ, and Baseline/Transition Dyspnea Index at baseline and six months. We compared mean changes in HRQL scores between groups of subjects whose disease severity changed over six months according to clinical anchors (FVC, DLCO, and dyspnea). We estimated the MID for each domain by using both anchor- and distribution-based approaches.Main resultsResults supported the validity of the SF-36 and SGRQ for use in longitudinal studies. Mean changes in domain scores differed significantly between subjects whose clinical status improved and those whose clinical status declined according to the anchors. MID estimates for the SF-36 ranged from 2-4 points and from 5-8 points for the SGRQ.ConclusionIn IPF, the SF-36 and SGRQ possess reasonable validity for differentiating subjects whose disease severity changes over time. More studies are needed to continue the validation process, to refine estimates of the MIDs for the SF-36 or SGRQ, and to determine if a disease-specific instrument will perform better than either of these.