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Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection. A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP. A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006). HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis.

The correlation between real-time PCR (rt-PCR) cycle threshold (Ct) values for respiratory viruses and clinical outcomes remains unclear. This study evaluates the association between Ct values and clinical outcomes in patients tested via point-of-care testing upon emergency department (ED) admission. This is a retrospective analysis of adults admitted to a French university hospital ED for suspected lower respiratory tract infections (LRTI) requiring oxygen therapy between 2019 and 2020. Ct values were assessed for their association with symptom duration and clinical outcomes (hospital length of stay (LOS), Intensive Care Unit (ICU) admission, and 28-day mortality) using zero-inflated negative binomial regression (ZINB) and logistic regression models, adjusted for age, sex, co-infection, and symptom duration. A total of 410 patients were included, with 37 (9%) having co-infections with two pathogens and 2 (0.5%) with three pathogens. The most common pathogens were human rhinovirus/enterovirus (HRV/EV) (26.3%), influenza A (24.9%), and SARS-CoV-2 (21.9%). Median symptom duration was 3 days [IQR: 2-7]. Of the patients, 308 (75.1%) were hospitalized, 74 (18%) required ICU care, and the 28-day mortality rate was 11.7% (n = 48). Multivariable analysis showed that higher Ct values for SARS-CoV-2 were associated with reduced odds of hospitalization (OR = 0.75, p = 0.04) and shorter LOS (x0.96 days per Ct unit increase, p = 0.04). Similar trends for shorter LOS were observed for HRV/EV and RSV but did not reach statistical significance. Conversely, higher influenza A Ct values were linked to longer LOS (x1.05 days per Ct unit increase, p = 0.025). Higher Ct values for SARS-CoV-2 were also associated with lower 28-day mortality (OR = 0.87, p = 0.049). Ct values were not associated with ICU admission for any virus. This study supports the association of higher Ct values with shorter LOS and lower mortality for SARS-CoV-2. In contrast, higher Ct values for influenza A were linked to longer LOS. Ct values were not predictive of ICU admission, underscoring the complexity of the relationship between viral load and clinical outcomes.

BackgroundHigh-density lipoproteins (HDLs), particles characterized by their reverse cholesterol transport function, display pleiotropic properties, including anti-inflammatory and antioxidant functions. Moreover, all lipoproteins (HDLs but also low-density lipoproteins (LDLs)) neutralize lipopolysaccharides, leading to increased bacterial clearance. These two lipoproteins decrease during sepsis, and an association between low lipoprotein levels and poor outcome was reported. The goals of this study were to characterize the lipid profile of septic patients hospitalized in our intensive care unit (ICU) and to determine the relationship with the outcome.MethodsA prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were assessed at admission (day 1), at day 3, and at ICU discharge. When available, a prehospitalization lipid profile collected prior to the patient’s hospitalization was compiled. Short-term and 1-year prognostic outcomes were prospectively assessed.ResultsA total of 205 patients were included. We found a decrease in HDL-C concentration between previous values and those at admission, followed by an additional decrease at day 3. At ICU discharge, the concentration was higher than that at day 3 but did not reach the concentration measured prior to hospitalization (prior HDL-C = 1.22 (1.04–1.57) mmol/l; day 1 HDL-C = 0.44 (0.29–0.70) mmol/l; day 3 HDL-C = 0.30 (0.25–0.48) mmol/l; and HDL-C at discharge = 0.65 (0.42–0.82) mmol/l). A similar trend was found for LDL-C (prior LDL-C = 2.7 (1.91–3.33) mmol/l; day 1 LDL-C = 1.0 (0.58–1.50) mmol/l; day 3 LDL-C = 1.04 (0.64–1.54) mmol/l; and LDL-C at discharge = 1.69 (1.26–2.21) mmol/l). Mixed models for repeated measures of lipoprotein concentrations showed a significant difference in HDL-C and LDL-C concentrations over time between survivors and nonsurvivors at day 28. An HDL-C concentration at admission of less than 0.4 mmol/l was associated with increased mortality at day 28 (log-rank test, p = 0.034) but not at 1 year (log-rank test, p = 0.24). An LDL-C concentration at admission of less than 0.72 mmol/l was associated with increased mortality at day 28 and at 1 year (log-rank test, p < 0.001 and p = 0.007, respectively). No link was found between prior lipid profile and mortality.ConclusionsWe showed no relationship between the prehospitalization lipid profile and patient outcome, but low lipoprotein levels in the ICU were strongly associated with short-term mortality.

High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU). A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin[greater than or equal to] 2N or aspartate aminotransferase/alanine aminotransferase concentrations [greater than or equal to] 2N. Short-term and one-year prognostic outcomes were prospectively assessed. A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers. Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis.

Extracorporeal membrane oxygenation (ECMO), a relevant technology for patients with acute respiratory distress syndrome (ARDS) or acute cardiac failure (ACF), is a frequent cause of systemic inflammatory response syndrome. During sepsis, HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) concentrations decrease, and an association between low lipoprotein levels and poor outcomes was reported. There are no data from patients undergoing ECMO. The goal of this study was to characterize the lipoprotein profiles of ICU patients requiring ECMO. All consecutive patients admitted for ARDS or ACF requiring ECMO were prospectively included. Daily lipoprotein levels and short-term prognosis outcome were assessed. 25 patients were included. On admission, lipoprotein concentrations were low, under the reference values ([HDL-C] = 0.6[0.4–0.8]mmol/L;[LDL-C] = 1.3[1.0–1.7]mmol/L). A statistically significant rise in lipoproteins overtime was observed during the ICU stay. We found no relationship between lipoproteins concentrations and mortality on Day-28 ( p  = 0.689 and p  = 0.979, respectively). Comparison of surviving patients with non-surviving patients did not reveal any differences in lipoproteins concentrations. Stratification between septic and non-septic patients demonstrated that septic patients had lower lipoproteins concentrations on admission (HDL-C: 0.5[0.3–0.6]mmol/l vs 0.8[0.6–0.9]mmol/l, p  = 0.003; LDL-C: 1.1[0.9–1.5]mmol/l vs 1.5[1.3–2.6]mmol/l; p  = 0.012), whereas these two groups were comparable in terms of severity and outcomes. HDL-C concentrations during ICU hospitalization were also significantly lower in the septic group than in the non-septic group ( p  = 0.035). In conclusion, Lipoprotein concentrations are low in patients requiring ECMO but are not associated with poor outcomes. The subpopulation of septic patients had lower lipoprotein levels overtime, which reinforces the potential key-role of these particles during sepsis.

High-density lipoproteins (HDLs) are synthesized by the liver and display endothelioprotective properties, including anti-inflammatory, antiapoptotic, antithrombotic and antioxidant effects. In both septic and chronic liver failure patients, a low HDL cholesterol (HDL-C) concentration is associated with overmortality. Whereas sepsis-associated liver dysfunction is poorly defined, the aim of this study was to characterize the relationship between liver dysfunction, lipoprotein concentrations and mortality in septic patients in the intensive care unit (ICU). A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride levels were assessed at admission. Sepsis-associated liver dysfunction was defined as a serum bilirubin[greater than or equal to] 2N or aspartate aminotransferase/alanine aminotransferase concentrations [greater than or equal to] 2N. Short-term and one-year prognostic outcomes were prospectively assessed. A total of 219 septic patients were included, and 15% of them presented with sepsis-associated liver dysfunction at admission. Low concentrations of lipoproteins were associated with mortality at Day 28 in the overall population. Sepsis-associated liver dysfunction at admission was associated with overmortality. In this subgroup, patients had a lower HDL-C concentration than patients without hepatic dysfunction (HDL-C = 0.31 [0.25, 0.55] mmol/L vs. 0.48 [0.29, 0.73] mmol/L, p = 0.0079) but there was no relationship with the outcome. Interestingly, no correlation was observed between lipoprotein concentrations and liver dysfunction markers. Sepsis-associated liver dysfunction at ICU admission is strongly associated with overmortality and is associated with a lower HDL-C concentration. However, in this subgroup of patients, HDL-C concentration had no relationship with mortality. Further exploratory studies are needed to better understand the interaction between lipoproteins and liver dysfunction during sepsis.

Objectives To assess interobserver agreement and clinical significance of chest CT reporting in patients suspected of COVID-19. Methods From 16 to 24 March 2020, 241 consecutive patients addressed to hospital for COVID-19 suspicion had both chest CT and SARS-CoV-2 RT-PCR. Eight observers (2 thoracic and 2 general senior radiologists, 2 junior radiologists, and 2 emergency physicians) retrospectively categorized each CT into one out of 4 categories (evocative, compatible for COVID-19 pneumonia, not evocative, and normal). Observer agreement for categorization between all readers and pairs of readers with similar experience was evaluated with the Kappa coefficient. The results of a consensus categorization were correlated to RT-PCR. Results Observer agreement across the 4 categories was good between all readers (κ value 0.61 95% CI 0.60–0.63) and moderate to good between pairs of readers (0.54–0.75). It was very good (κ 0.81 95% CI 0.79–0.83), fair (κ 0.32 95% CI 0.29–0.34), moderate (κ 0.56 95% CI 0.54–0.58), and moderate (0.58 95% CI 0.56–0.61) for the categories evocative, compatible, not evocative, and normal, respectively. RT-PCR was positive in 97%, 50%, 31%, and 11% of cases in the respective categories. Observer agreement was lower ( p < 0.001) and RT-PCR positive cases less frequently categorized evocative in the presence of an underlying pulmonary disease ( p < 0.001). Conclusion Interobserver agreement for chest CT reporting using categorization of findings is good in patients suspected of COVID-19. Among patients considered for hospitalization in an epidemic context, CT categorized evocative is highly predictive of COVID-19, whereas the predictive value of CT decreases between the categories compatible and not evocative. Key Points • In patients suspected of COVID-19, interobserver agreement for chest CT reporting into categories is good, and very good to categorize CT “evocative.” • Chest CT can participate in estimating the likelihood of COVID-19 in patients presenting to hospital during the outbreak, CT categorized “evocative” being highly predictive of the disease whereas almost a third of patients with CT “not evocative” had a positive RT-PCR in our study. • Observer agreement is lower and CTs of positive RT-PCR cases less frequently “evocative” in presence of an underlying pulmonary disease.

Background The individual factors associated to Frequent Users (FUs) in Emergency Departments are well known. However, the characteristics of their geographical distribution and how territorial specificities are associated and intertwined with ED use are limited. Investigating healthcare use and territorial factors would help targeting local health policies. We aim at describing the geographical distribution of ED’s FUs within the Paris region. Methods We performed a retrospective analysis of all ED visits in the Paris region in 2015. Data were collected from the universal health insurance’s claims database. Frequent Users (FUs) were defined as having visited ≥3 times any ED of the region over the period. We assessed the FUs rate in each geographical unit (GU) and assessed correlations between FUs rate and socio-demographics and economic characteristics of GUs. We also performed a multidimensional analysis and a principal component analysis to identify a typology of territories to describe and target the FUs phenomenon. Results FUs accounted for 278,687 (11.7%) of the 2,382,802 patients who visited the ED, living in 232 GUs. In the region, median FUs rate in each GU was 11.0% [interquartile range: 9.5–12.5]. High FUs rate was correlated to the territorial markers of social deprivation. Three different categories of GU were identified with different profiles of healthcare providers densities. Conclusion FUs rate varies between territories and is correlated to territorial markers of social deprivation. Targeted public policies should focus on disadvantaged territories.

Influenza vaccination (IV) coverage remains low in France. Objectives were to assess patient knowledge and behaviors and missed opportunities for vaccination (MO) and their impact on vaccine uptake. This is a prospective-observational study, including emergency department patients at risk for severe influenza. Patients were interviewed about their knowledge and behaviors. We evaluated the health-care voucher scheme (HCVS) and MO. 868 patients were included. Vaccine uptake was 33.2%, 42% of patients knew about the possible severity of influenza, 23% thought that they were not at risk for severe influenza, 39% knew that they have an indication for the vaccine, and 4.3% to 11.5% expressed reservations concerning IV side effects and effectiveness. HCVS was used by 44.3% of patients, but only 14.8% had been vaccinated. MO were reported by 484 patients (69.4%) declaring 1104 consultations and 148 IV propositions (86.6%). Predictors of vaccine uptake (p<0.0001) were: knowledge of serious and fatal influenza forms [OR 0.36 (CI95% 0.25-0.5)]; confidence in influenza vaccine effectiveness [0.38 (0.2-0.7)]; opposition to vaccines [0.22 (0.1-0.48)]; visit to general practitioner [4.53 (2.9-7.1)]; general practitioner proposed IV [2.1 (1.2-3.4)]. Our results indicate that high rate of missed opportunities, some patient behaviors and general practitioner visits may explain low influenza vaccine uptake, and that HCVS use is a complex process. Of interest, we found that the patient's knowledge of the potential severity of influenza is not sufficient to promote vaccine, suggesting that the information strategy must be adapted to each patient behavior.

Rapid identification of patients with high suspicion of COVID-19 will become a challenge with the co-circulation of multiple respiratory viruses (RVs). We have identified clinical or biological characteristics to help distinguish SARS-CoV-2 from other RVs. We used a prospective cohort including all consecutive patients admitted through the emergency department's (ED) and presenting respiratory symptoms from November 2019 to April 2020. Patients were tested for RV using multiplex polymerase chain reaction (mPCR) and SARS-CoV-2 RT-PCR. 203/508 patients were positive for an RV during the non-SARS-CoV-2 epidemic period (November to February), and 268/596 patients were SARS-CoV-2 positive during the SARS-CoV-2 epidemic (March to April). Younger age, male gender, fever, absence of expectoration and absence of chronic lung disease were statistically associated with SARS-CoV-2 detection. Combining these variables allowed for the distinguishing of SARS-CoV-2 infections with 83, 65, 75 and 76% sensitivity, specificity, PPV and NPV, respectively. Patients' characteristics associated with a positive PCR are common between SARS-CoV-2 and other RVs, but a simple discrimination of strong SARS-CoV-2 suspicion with a limited set of clinical features seems possible. Such scoring could be useful but has to be prospectively evaluated and will not eliminate the need for rapid PCR assays.