For whom does the bell toll? oneyear follow-up on ed responder burnout during the COVID-19 pandemic

BACKGROUND: The COVID-19 (COVID) pandemic has caused incalculable damages throughout the U.S., with over 34-million infections and 600,000 deaths as of July 2021. Many medical personnel on the frontline, especially within emergency departments, experienced immense burnout. Although the extent of the burnout at the beginning of the pandemic has been reported in the literature, there is a paucity of data on how that has evolved over time. We aimed to survey providers a year into the pandemic on stress and burnout in the setting of new vaccine availability. METHODS: Two online surveys were distributed among healthcare providers at a tertiary academic center between 2020 and 2021. The initial survey was composed of questions evaluating the level of burnout and risk perception. The latter had the same questions for comparison, as well as questions regarding vaccination status and the Professional Quality of Life Scale (PROQOL). Chi-squared tests were used to compare the results. RESULTS: There were 63 responses in 2020 and 78 responses in 2021. 94% received the COVID vaccine in 2021. Measures of risk perception, specifically “Feels job is imposing great risk” and “Afraid of falling ill with COVID” saw statistically significant decreases (87% to 62%, p= 0.001;76% to 45%, p< 0.001, respectively). Meanwhile, while the point estimate for “feeling extra stress at work” and “thinking about resigning” also decreased, neither were statistically significant (85% to 76%, p=0.148;11% to 9%, p= 0.673, respectively). The PROQOL results from 2021 showed most responders experienced either moderate or high levels of Burnout and Post-traumatic stress, but also Compassion Satisfaction (85%, 62%, and 96%, respectively). CONCLUSIONS: During the 1-year study period there were significant improvements in terms of risk perception, though burnout and stress remained high. The reduction in risk perception may be related to vaccination, given the high rate of vaccination among this group and temporal correlation. However further research is necessary to support this relationship, as well as identify other potential factors to help reduce burnout in future pandemics.

Correlational analysis of eaa with other inflammatory markers in critically ill SARS-CoV-2 patients

INTRODUCTION: The Endotoxin Activity Assay (EAA) is a lab analysis to detect primed neutrophils in inflammatory states such as sepsis. Its use as a potential biomarker in SARS-CoV-2 patients has not been previously studied. Other markers such as CRP, ESR, LDH, ferritin, d-dimer, WBC count, procalcitonin, and IL-6 have all been shown to be reliable predictors of inflammatory states. We sought to find out the correlation between EAA and other inflammatory markers in patients admitted to the ICU with SARS-CoV-2 infection. METHODS: This is a prospective cohort analysis of SARSCoV- 2 patients admitted to the ICU at a single academic hospital from March to June 2020. Values for all study variables were obtained from each COVID-positive patient on days 1, 2, and 7 of ICU stay, and also for the onset of mechanical ventilation, vasopressors, acute kidney injury, and increase in ferritin >50% from the level at admission. Logistic and linear regression analyses were used to compare EAA with IL-6, CRP, ferritin, ESR, LDH, d-dimer, WBC, and procalcitonin. RESULTS: A total of 214 EAA results were recorded from 99 patients, with characteristics of: median age 61.84, 45% female, 74% Black, 21% Hispanic, 4% White, and 1% Asian. A significant linear regression equation was found between EAA and CRP: F (1, 168)=19.20, p<.0001, with an R2 of 0.1031 and Pearson's r of 0.32109, indicating a moderate correlation. Significant Spearman Correlation Coefficients were found between EAA and CRP, LDH, and D-dimer: ρ (169)=0.2896, p=0.0001;ρ (180)=0.179, p=0.01;ρ (165)=0.169, p=0.03, suggesting a mild correlation. Other markers did not show a significant correlation with EAA: IL-6 ρ (35)=0.144, p=0.40;Ferritin ρ (173)=0.0533 p=0.48;ESR ρ (37)=0.067, p=0.69;WBC ρ (213)=0.057, p=0.40;Procalcitonin ρ (14)=0.014, p=0.96. CONCLUSIONS: EAA has a statistically significant positive correlation with CRP, LDH, and D-dimer, but not with IL-6, ferritin, ESR, WBC, and procalcitonin. Further studies exploring the relationship between EAA and other biomarkers can establish the validity and reliability of EAA in inflammatory states such as COVID sepsis. This can help identify the role of EAA as an adjunct biomarker to assess the efficacy of therapeutic strategies and to prognosticate and predict mortality in patients with SARS-CoV-19.

Endotoxin activity as a marker for disease severity in SARS-CoV-2 patients in the ICU

INTRODUCTION: Endotoxin Activity Assay (EAA), which measures the chemiluminescent response of the neutrophils to endotoxin using an anti-endotoxin antibody, has been used to predict mortality in patients with gram-negative sepsis. Recent evidence has shown that this indirect method of endotoxin measurement does not account for other causes that may excite or depress neutrophil activity. We sought to evaluate the levels of EAA in patients with severe COVID-19 infections without bacteremia but rather a systemic inflammatory state and acute respiratory distress syndrome. METHODS: This is a single-center, prospective cohort analysis of SARS-CoV-2-positive patients admitted to the ICU at a single academic hospital, from March to June 2020. EAA levels were obtained from each COVID-positive patient at ICU admission. Demographics, as well as the development of bacteremia on blood culture, were abstracted from medical records. Initial EAA values were categorized into low EAA (<0.4), intermediate EAA (0.41-0.60), high EAA (0.61-0.80), and severely high EAA (>0.80). RESULTS: A total of 78 patients were included in the study, with baseline characteristics as follows: mean age 62.9 years, 46% female, with a racial distribution of 72% Black, 15% White, and 4% Asian. Of the 78 COVID-positive patients, only eight were confirmed positive for bacteremia, while the remaining patients had two negative blood cultures. Of the eight bacteremic patients, the EAA level was low in zero patients, intermediate in three, high in four, and severely high in one patient, resulting in 100% of patients with intermediate or higher EAA level. Of the 70 patients without bacteremia, the EAA level was low in 13, intermediate in 10, high in 34, and severely high in 13, resulting in 81.4% of patients with an intermediate or higher EAA level. CONCLUSIONS: Elevated levels of EAA representing significant endotoxemia are frequently observed in nonbacteremic patients with severe SARS-CoV-2 viral infection. The source of the endotoxemia is unidentified. Possible explanations include gut bacterial translocation from the endothelial cell dysfunction that is known to occur with COVID 19 infection, or that EAA is an indicator of a primed neutrophil state. Further investigation of the elevated EAA levels seen in COVID -19 infections is warranted.

Endotoxin levels, as measured by eaa, are elevated in COVID-19 patients admitted to the ICU

INTRODUCTION/HYPOTHESIS: Endotoxin Activity Assay (EAA), which measures the chemiluminescent response of the neutrophils to endotoxin using an anti-endotoxin antibody, has been used to predict mortality in patients with gramnegative sepsis. Recent evidence has shown that this indirect method of endotoxin measurement does not account for other causes that may excite or depress neutrophil activity. We sought to evaluate the levels of EAA in patients with severe COVID-19 infections without bacteremia but rather a systemic inflammatory state and acute respiratory distress syndrome. METHODS: This is a single-center, prospective cohort analysis of SARS-CoV-2-positive patients admitted to the ICU at a single academic hospital, from March to June 2020. EAA levels were obtained from each COVID-positive patient at ICU admission. Demographics, as well as the development of bacteremia on blood culture, were abstracted from medical records. Initial EAA values were categorized into low EAA (<0.4), intermediate EAA (0.41-0.60), high EAA (0.61-0.80), and severely high EAA (>0.80). RESULTS: A total of 78 patients were included in the study, with baseline characteristics as follows: mean age 62.9 years, 46% female, with a racial distribution of 72% Black, 15% White, and 4% Asian. Of the 78 COVID-positive patients, only eight were confirmed positive for bacteremia, while the remaining patients had two negative blood cultures. Of the eight bacteremic patients, the EAA level was low in zero patients, intermediate in three, high in four, and severely high in one patient, resulting in 100% of patients with intermediate or higher EAA level. Of the 70 patients without bacteremia, the EAA level was low in 13, intermediate in 10, high in 34, and severely high in 13, resulting in 81.4% of patients with an intermediate or higher EAA level. CONCLUSIONS: Elevated levels of EAA representing significant endotoxemia are frequently observed in nonbacteremic patients with severe SARS-CoV-2 viral infection. The source of the endotoxemia is unidentified. Possible explanations include gut bacterial translocation from the endothelial cell dysfunction that is known to occur with COVID 19 infection, or that EAA is an indicator of a primed neutrophil state. Further investigation of the elevated EAA levels seen in COVID -19 infections is warranted.

Potential biomarkers for severe ards in the setting of SARS-CoV-2 ICU admission

INTRODUCTION: Acute respiratory disease syndrome (ARDS) is due to compromised lung oxygen exchange in the setting of severe alveolar inflammation. This can be assessed and diagnosed using the ratio of alveolar oxygen saturation (PaO2) to the fraction of inspired oxygen (FiO2), P-F ratio. In hospitalized COVID-19 patients, the role of trending inflammatory markers to categorize levels of ARDS severity in the clinical setting has yet to be established. In this study, we describe the correlational relationship of five biomarkers to the PaO2/FiO2 ratio (P-F ratio), a key diagnostic criterion, and a measure of severity in ARDS. METHODS: This is a prospective cohort analysis of SARs-CoV-2 patients admitted to the ICU at a single urban academic center from March to June 2020. Levels of Endotoxin activity assay (EAA), CRP, ferritin, LDH, and d-dimer were obtained from intubated patients throughout their ICU stay. PaO2 and FiO2 values matching the same days as the biomarkers and demographic information were abstracted from the medical record. The inflammatory markers were matched to the P-F ratios of the same day, and Spearman Correlation Coefficients were performed to detect the relationship between them. RESULTS: A total of 45 intubated COVID patients were included, with baseline characteristics of: median age 55 years and 33% female, 62% Black, 27% Hispanic, 9% Asian, and 2% White. Spearman Correlation Coefficient (ρ) showed statistically significant relationships between P/F ratios and EAA, IL-6, CRP, and ESR, with respective values of: ρ (89)=-0.2366, p=0.02;ρ (13)=-0.7143, p=0.006;ρ (77)=-0.3670, p=0.001;ρ (17)=-0.5569, p=0.02. ρ was also calculated between P/F ratios and Ferritin, D-dimer, WBC, and LDH with respective values of: ρ (77)=0.0819, p=0.47;ρ (78)=-0.2105, p=0.06;ρ (88)=-0.1046, p=0.33;ρ (73)=0.0420, p=0.72, showing no statistically significant relationship between these variables. CONCLUSIONS: EAA, IL-6, CRP, and ESR levels had a statistically significant negative correlation with the P-F ratio. Elevations in these biomarkers correlated with worsening P-F ratios, suggesting that they could serve as useful biomarkers to predict ARDS severity. Additional studies are needed to further understand the trend of these biomarkers and validate their clinical use in prognostication in ARDS.

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the US (preprint)

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. In 2020, the COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized hundreds of thousands of specific predictions from more than 50 different academic, industry, and independent research groups. This manuscript systematically evaluates 23 models that regularly submitted forecasts of reported weekly incident COVID-19 mortality counts in the US at the state and national level. One of these models was a multi-model ensemble that combined all available forecasts each week. The performance of individual models showed high variability across time, geospatial units, and forecast horizons. Half of the models evaluated showed better accuracy than a naive baseline model. In combining the forecasts from all teams, the ensemble showed the best overall probabilistic accuracy of any model. Forecast accuracy degraded as models made predictions farther into the future, with probabilistic accuracy at a 20-week horizon more than 5 times worse than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks. f