Derivation and validation of a risk-stratification model for patients with probable or proven COVID-19 in EDs: the revised HOME-CoV score.

BACKGROUND: The HOME-CoV (Hospitalisation or Outpatient ManagEment of patients with SARS-CoV-2 infection) score is a validated list of uniquely clinical criteria indicating which patients with probable or proven COVID-19 can be treated at home. The aim of this study was to optimise the score to improve its ability to discriminate between patients who do and do not need admission. METHODS: A revised HOME-CoV score was derived using data from a previous prospective multicentre study which evaluated the original Home-CoV score. Patients with proven or probable COVID-19 attending 34 EDs in France, Monaco and Belgium between April and May 2020 were included. The population was split into a derivation and validation sample corresponding to the observational and interventional phases of the original study. The main outcome was non-invasive or invasive ventilation or all-cause death within 7 days following inclusion. Two threshold values were defined using a sensitivity of >0.9 and a specificity of >0.9 to identify low-risk and high-risk patients, respectively. The revised HOME-CoV score was then validated by retrospectively applying it to patients in the same EDs with proven or probable COVID-19 during the interventional phase. The revised HOME-CoV score was also tested against original HOME-CoV, qCSI, qSOFA, CRB65 and SMART-COP in this validation cohort. RESULTS: There were 1696 patients in the derivation cohort, of whom 65 (3.8%) required non-invasive ventilation or mechanical ventilation or died within 7 days and 1304 patients in the validation cohort, of whom 22 (1.7%) had a progression of illness. The revised score included seven clinical criteria. The area under the curve (AUC) was 87.6 (95% CI 84.7 to 90.6). The cut-offs to define low-risk and high-risk patients were <2 and >3, respectively. In the validation cohort, the AUC was 85.8 (95% CI 80.6 to 91.0). A score of <2 qualified 73% of patients as low risk with a sensitivity of 0.77 (0.55-0.92) and a negative predictive value of 0.99 (0.99-1.00). CONCLUSION: The revised HOME-CoV score, which does not require laboratory testing, may allow accurate risk stratification and safely qualify a significant proportion of patients with probable or proven COVID-19 for home treatment.

Association between admission biomarkers and clinical outcome in older adults diagnosed with an infection in the emergency department.

INTRODUCTION: In older adults, prognostic performances of admission biomarkers have been poorly investigated. This study aims to compare the prognostic abilities of usual admission biomarkers, especially PCT and CRP, for major clinical outcomes, comparing older to younger adults diagnosed with an infection in the ED, and to investigate the prognostic abilities of PCT and CRP depending on the glomerular filtration rate (GFR). METHODS: It was an observational, single-center, retrospective study, conducted in the Reims University Hospital, France. Endpoints were bacteremia, septic shock, and in-hospital mortality, related to the same ED visit. RESULTS: Over 1 year, 852 patients were included with 291 (34.2%) ≥75 years, and 127 (15.3%) patients had a GFR <30 mL.min-1.1.73 m2. Overall, 74 bacteremia, 56 septic shock and 82 in-hospital deaths have been observed. Prognostic abilities of admission biomarkers tended to be systematically lower in older compared to younger adults (PCT and CRP AUROC for bacteremia were, respectively, 0.71 and 0.62 in older adults vs 0.75 and 0.70 in younger adults; PCT and CRP AUROC for septic shock were, respectively, 0.71 and 0.66 in older adults vs 0.82 and 0.68 in younger adults). PCT showed a significant discriminating power for septic shock and in-hospital mortality only for GFR ≥ 30, and CRP showed a significant discriminating power for bacteremia and septic shock only for GFR ≥60. CONCLUSION: Caution must be taken when interpreting admission biomarkers, as their prognostic abilities are lower in older adults or in patients with renal insufficiency diagnosed with an infection.

Silent Hypoxemia in the Emergency Department: A Retrospective Cohort of Two Clinical Phenotypes in Critical COVID-19.

Introduction: Understanding hypoxemia, with and without the clinical signs of acute respiratory failure (ARF) in COVID-19, is key for management. Hence, from a population of critical patients admitted to the emergency department (ED), we aimed to study silent hypoxemia (Phenotype I) in comparison to symptomatic hypoxemia with clinical signs of ARF (Phenotype II). Methods: This multicenter study was conducted between 1 March and 30 April 2020. Adult patients who were presented to the EDs of nine Great-Eastern French hospitals for confirmed severe or critical COVID-19, who were then directly admitted to the intensive care unit (ICU), were retrospectively included. Results: A total of 423 critical COVID-19 patients were included, out of whom 56.1% presented symptomatic hypoxemia with clinical signs of ARF, whereas 43.9% presented silent hypoxemia. Patients with clinical phenotype II were primarily intubated, initially, in the ED (46%, p < 0.001), whereas those with silent hypoxemia (56.5%, p < 0.001) were primarily intubated in the ICU. Initial univariate analysis revealed higher ICU mortality (29.2% versus 18.8%, p < 0.014) and in-hospital mortality (32.5% versus 18.8%, p < 0.002) in phenotype II. However, multivariate analysis showed no significant differences between the two phenotypes regarding mortality and hospital or ICU length of stay. Conclusions: Silent hypoxemia is explained by various mechanisms, most physiological and unspecific to COVID-19. Survival was found to be comparable in both phenotypes, with decreased survival in favor of Phenotype II. However, the spectrum of silent to symptomatic hypoxemia appears to include a continuum of disease progression, which can brutally evolve into fatal ARF.

The Impact of Age on In-Hospital Mortality in Critically Ill COVID-19 Patients: A Retrospective and Multicenter Study.

Introduction: For the past two years, healthcare systems worldwide have been battling the ongoing COVID-19 pandemic. Several studies tried to find predictive factors of mortality in COVID-19 patients. We aimed to research age as a predictive factor associated with in-hospital mortality in severe and critical SARS-CoV-2 infection. Methods: Between 1 March and 20 April 2020, we conducted a multicenter and retrospective study on a cohort of severe COVID-19 patients who were all hospitalized in the Intensive Care Unit (ICU). We led our study in nine hospitals of northeast France, one of the pandemic's epicenters in Europe. Results: The median age of our study population was 66 years (58−72 years). Mortality was 24.6% (CI 95%: 20.6−29%) in the ICU and 26.5% (CI 95%: 22.3−31%) in the hospital. Non-survivors were significantly older (69 versus 64 years, p < 0.001) than the survivors. Although a history of cardio-vascular diseases was more frequent in the non-survivor group (p = 0.015), other underlying conditions and prior level of autonomy did not differ between the two groups. On multivariable analysis, age appeared to be an interesting predictive factor of in-hospital mortality. Thus, age ranges of 65 to 74 years (OR = 2.962, CI 95%: 1.231−7.132, p = 0.015) were predictive of mortality, whereas the group of patients aged over 75 years was not (OR = 3.084, CI 95%: 0.952−9.992, p = 0.06). Similarly, all comorbidities except for immunodeficiency (OR = 4.207, CI 95%: 1.006−17.586, p = 0.049) were not predictive of mortality. Finally, survival follow-up was obtained for the study population. Conclusion: Age appears to be a relevant predictive factor of in-hospital mortality in cases of severe or critical SARS-CoV-2 infection.

Prognostic Value of C-Reactive Protein to Lymphocyte Ratio (CLR) in Emergency Department Patients with SARS-CoV-2 Infection.

(1) Introduction: According to recent studies, the ratio of C-reactive-protein to lymphocyte is more sensitive and specific than other biomarkers associated to systemic inflammatory processes. This study aimed to determine the prognostic value of CLR on COVID-19 severity and mortality at emergency department (ED) admission. (2) Methods: Between 1 March and 30 April 2020, we carried out a multicenter and retrospective study in six major hospitals of northeast France. The cohort was composed of patients hospitalized for a confirmed diagnosis of moderate to severe COVID-19. (3) Results: A total of 1,035 patients were included in this study. Factors associated with infection severity were the CLR (OR: 1.001, CI 95%: (1.000-1.002), p = 0.012), and the lymphocyte level (OR: 1.951, CI 95%: (1.024-3.717), p = 0.042). In multivariate analysis, the only biochemical factor significantly associated with mortality was lymphocyte rate (OR: 2.308, CI 95%: (1.286-4.141), p = 0.005). The best threshold of CLR to predict the severity of infection was 78.3 (sensitivity 79%; specificity 47%), and to predict mortality, was 159.5 (sensitivity 48%; specificity 70%). (4) Conclusion: The CLR at admission to the ED could be a helpful prognostic biomarker in the early screening and prediction of the severity and mortality associated with SARS-CoV-2 infection.

Clinical Outcome Predictive Value of Procalcitonin in Patients Suspected with Infection in the Emergency Department.

Procalcitonin (PCT) may be useful for early risk stratification in the emergency department (ED), but the transposition of published data to routine emergency practice is sometimes limited. An observational retrospective study was conducted in the adult ED of the Reims University Hospital (France). Over one year, 852 patients suspected of infection were included, of mean age 61.7 years (SD: 22.6), and 624 (73.2%) were hospitalized following ED visit. Overall, 82 (9.6%) patients died during their hospitalization with an odds ratio (OR) of 5.10 (95% CI: 2.19-11.87) for PCT ≥ 0.5, in multivariate logistic regression analyses. Moreover, 78 (9.2%) patients were admitted to an ICU, 74 (8.7%) had attributable bacteremia, and 56 (6.6%) evolved toward septic shock with an OR of 4.37 (2.08-9.16), 6.38 (2.67-15.24), and 6.38 (2.41-16.86), respectively, for PCT ≥ 0.5. The highest discriminatory values were found for patients with age <65 years, but PCT lost its discrimination power for in-hospital mortality in patients with a bronchopulmonary infection site or a temperature ≥37.8°C and for ICU admission in patients with severe clinical presentations. PCT could be helpful in risk stratification, but several limitations must be considered, including being sometimes outperformed by a simple clinical examination.

Neutrophil-to-Lymphocyte Ratio and Early Variation of NLR to Predict In-Hospital Mortality and Severity in ED Patients with SARS-CoV-2 Infection.

(1) Introduction: The neutrophil-to lymphocyte ratio is valued as a predictive marker in several inflammatory diseases. For example, an increasing NLR is a risk factor of mortality in sepsis. It also appears to be helpful in other settings such as cancer. The aim of our work was to study the prognostic value of NLR for disease severity and mortality in patients infected with SARS-CoV-2 upon their admission to the Emergency Department (ED) and its early variation (ΔNLR) in the first 24 h of management (H-24). (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter and retrospective cohort study of patients with moderate or severe coronavirus disease 19 (COVID-19), who were all hospitalized after presenting to the ED. (3) Results: A total of 1035 patients were included in our study. Factors associated with infection severity were C-reactive protein level (OR: 1.007, CI 95%: [1.005-1.010], p < 0.001), NLR at H-24 (OR: 1.117, CI 95%: [1.060-1.176], p < 0.001), and ΔNLR (OR: 1.877, CI 95%: [1.160-3.036], p: 0.01). The best threshold of ΔNLR to predict the severity of infection was 0.222 (sensitivity 56.1%, specificity 68.3%). In multivariate analysis, the only biochemical factor significantly associated with mortality was again ΔNLR (OR: 2.142, CI 95%: ([1.132-4.056], p: 0.019). The best threshold of ΔNLR to predict mortality was 0.411 (sensitivity 53.3%; specificity 67.3%). (4) Conclusion: The NLR and its early variation (ΔNLR) could help physicians predict both severity and mortality associated with SARS-CoV-2 infection, hence contributing to optimized patient management (accurate triage and treatment).

Outpatient Management of Patients With COVID-19: Multicenter Prospective Validation of the Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection Rule to Discharge Patients Safely.

BACKGROUND: The Hospitalization or Outpatient Management of Patients With SARS-CoV-2 Infection (HOME-CoV) rule is a checklist of eligibility criteria for home treatment of patients with COVID-19, defined using a Delphi method. RESEARCH QUESTION: Is the HOME-CoV rule reliable for identifying a subgroup of COVID-19 patients with a low risk of adverse outcomes who can be treated at home safely? STUDY DESIGN AND METHODS: We aimed to validate the HOME-CoV rule in a prospective, multicenter study before and after trial of patients with probable or confirmed COVID-19 who sought treatment at the ED of 34 hospitals. The main outcome was an adverse evolution, that is, invasive ventilation or death, occurring within the 7 days after patient admission. The performance of the rule was assessed by the false-negative rate. The impact of the rule implementation was assessed by the absolute differences in the rate of patients who required invasive ventilation or who died and in the rate of patients treated at home, between an observational and an interventional period after implementation of the HOME-CoV rule, with propensity score adjustment. RESULTS: Among 3,000 prospectively enrolled patients, 1,239 (41.3%) demonstrated a negative HOME-CoV rule finding. The false-negative rate of the HOME-CoV rule was 4 in 1,239 (0.32%; 95% CI, 0.13%-0.84%), and its area under the receiver operating characteristic curve was 80.9 (95% CI, 76.5-85.2). On the adjusted populations, 25 of 1,274 patients (1.95%) experienced an adverse evolution during the observational period vs 12 of 1,274 patients (0.95%) during the interventional period: -1.00 (95% CI, -1.86 to -0.15). During the observational period, 858 patients (67.35%) were treated at home vs 871 patients (68.37%) during the interventional period: -1.02 (95% CI, -4.46 to 2.26). INTERPRETATION: A large proportion of patients treated in the ED with probable or confirmed COVID-19 have a negative HOME-CoV rule finding and can be treated safely at home with a very low risk of complications. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04338841; URL: www.clinicaltrials.gov.

Lack of admission biomarkers' clinical utility in outcomes prediction in patients suspected with infection in the emergency department.

INTRODUCTION: Initial procalcitonin (PCT) levels may fail in mortality and septic shock prediction and raise cost-effectiveness issues. Since measurement of lactate, C-reactive protein (CRP), white blood cells and neutrophils is common in the emergency department (ED), we compared prediction abilities of these biomarkers to PCT. METHODS: From January 1st to December 31st, 2018, an observational, single center, retrospective study was conducted in the adult ED of the Reims University Hospital (France). Endpoints were bacteremia, septic shock, and in-hospital mortality, related to the same ED visit. RESULTS: Over one year, 459 patients suspected with infection were included, of mean age 60.4 years (SD: 22.0), with 50.8% male, and 364 (79.3%) were hospitalized following ED visit. Overall, 45 (9.8%) patients had a bacteremia, 39 (8.5%) a septic shock and 54 (11.8%) died during their hospitalization. PCT and CRP showed the best discrimination for bacteremia, with an area under curve (AUC) of 0.68 for PCT and 0.65 for CRP. PCT and lactate showed similar good discriminative power for septic shock, with an AUC of 0.78 for both, and poor discrimination for in-hospital mortality, with an AUC of 0.62 for PCT and 0.69 for lactate. Systolic blood pressure and pulse oximetry showed similar discrimination for septic shock as PCT or lactate, while they showed higher discrimination for in-hospital mortality than PCT. CONCLUSION: Usual admission biomarkers lack clinical utility in predicting septic shock or in-hospital mortality. CRP and PCT are poorly efficient in predicting bacteremia.

Do Blood Eosinophils Predict in-Hospital Mortality or Severity of Disease in SARS-CoV-2 Infection? A Retrospective Multicenter Study.

INTRODUCTION: Healthcare systems worldwide have been battling the ongoing COVID-19 pandemic. Eosinophils are multifunctional leukocytes implicated in the pathogenesis of several inflammatory processes including viral infections. We focus our study on the prognostic value of eosinopenia as a marker of disease severity and mortality in COVID-19 patients. METHODS: Between 1 March and 30 April 2020, we conducted a multicenter and retrospective study on a cohort of COVID-19 patients (moderate or severe disease) who were hospitalized after presenting to the emergency department (ED). We led our study in six major hospitals of northeast France, one of the outbreak's epicenters in Europe. RESULTS: We have collected data from 1035 patients, with a confirmed diagnosis of COVID-19. More than three quarters of them (76.2%) presented a moderate form of the disease, while the remaining quarter (23.8%) presented a severe form requiring admission to the intensive care unit (ICU). Mean circulating eosinophils rate, at admission, varied according to disease severity (p < 0.001), yet it did not differ between survivors and non-survivors (p = 0.306). Extreme eosinopenia (=0/mm3) was predictive of severity (aOR = 1.77, p = 0.009); however, it was not predictive of mortality (aOR = 0.892, p = 0.696). The areas under the Receiver operating characteristics (ROC) curve were, respectively, 58.5% (CI95%: 55.3-61.7%) and 51.4% (CI95%: 46.8-56.1%) for the ability of circulating eosinophil rates to predict disease severity and mortality. CONCLUSION: Eosinopenia is very common and often profound in cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Eosinopenia was not a useful predictor of mortality; however, undetectable eosinophils (=0/mm3) were predictive of disease severity during the initial ED management.

Pre-Hospital Management of Critically Ill Patients with SARS-CoV-2 Infection: A Retrospective Multicenter Study.

INTRODUCTION: The COVID-19 outbreak had a major impact on healthcare systems worldwide. Our study aims to describe the characteristics and therapeutic emergency mobile service (EMS) management of patients with vital distress due to COVID-19, their in-hospital care pathway and their in-hospital outcome. METHODS: This retrospective and multicentric study was conducted in the six main centers of the French Greater East region, an area heavily impacted by the pandemic. All patients requiring EMS dispatch and who were admitted straight to the intensive care unit (ICU) were included. Clinical data from their pre-hospital and hospital management were retrieved. RESULTS: We included a total of 103 patients (78.6% male, median age 68). In the initial stage, patients were in a critical condition (median oxygen saturation was 72% (60-80%)). In the field, 77.7% (CI 95%: 71.8-88.3%) were intubated. Almost half of our population (45.6%, CI 95%: 37.1-56.9%) had clinical Phenotype 1 (silent hypoxemia), while the remaining half presented Phenotype 2 (acute respiratory failure). In the ICU, a great number had ARDS (77.7%, CI 95% 71.8-88.3% with a PaO2/FiO2 < 200). In-hospital mortality was 33% (CI 95%: 24.6-43.3%). The two phenotypes showed clinical and radiological differences (respiratory rate, OR = 0.98, p = 0.02; CT scan lesion extension >50%, OR = 0.76, p < 0.03). However, no difference was found in terms of overall in-hospital mortality (OR = 1.07, p = 0.74). CONCLUSION: The clinical phenotypes appear to be very distinguishable in the pre-hospital field, yet no difference was found in terms of mortality. This leads us to recommend an identical management in the initial phase, despite the two distinct presentations.

Early Management of Transient Ischemic Attack in Emergency Departments in France.

INTRODUCTION: Emergency departments play a key role in the diagnosis and treatment of transient ischemic attacks, but limited data are available about the early management of such patients in emergency wards. Therefore, we aimed to evaluate emergency physicians' management of transient ischemic attack and analyze variations factors. METHODS: A multicenter survey among emergency physicians of the Grand Est region network (Est-RESCUE) was conducted from January 28th to March 28th, 2019. Medical and administrative data were collected by the same network and the national directory of medical resources. RESULTS: Among 542 emergency physicians recipients, 78 answered (14%) and 71 were finally included, practicing in 25 public hospitals homogeneously distributed across the territory, including 3 university hospitals. A cerebral magnetic resonance imaging was obtained for 75%-100% of patients by 4.3% of responders, 36.4% of which were performed within more than 24 hours. A cardiac monitoring was prescribed in 75%-100% of cases by 32.4% of responders. A neurologic consultation was routinely requested by 84.6% of responders practicing in a university hospital and 36.8% of responders practicing in a community hospital (P = .02). Patients were hospitalized in a neurovascular unit in 75%-100% of cases by 17.4% of responders, which happened more likely in university hospitals (P < .001). CONCLUSIONS: Transient ischemic attack suffers from management disparities across territories, due to limited access to technical facilities and neurologic consultations. Therefore, international recommendations are too often not followed. Implementation of territorial neurovascular tracks may help to standardize the management of these patients.

Evaluation of ceftriaxone prescriptions in the emergency department of a university hospital: an urgent need for improvement and alternative therapy.

To evaluate the relevance of ceftriaxone prescriptions in an emergency department of a university hospital and suggest whenever possible an antibiotic alternative with a lower ecological impact. All ceftriaxone prescriptions in the first complete week of each month during the year 2016, in the emergency department of the Grenoble university hospital, have been analyzed by an IDS referent in antibiotic prescriptions. Ceftriaxone prescription was considered appropriate if justified (an antibiotic must be used), relevant (ceftriaxone is a good choice), and adapted (in terms of dose, route, and period of administration), regardless of a potential antibiotic association, consistent with international recommendations. We considered patient outcome regarding the quality of initial prescription. Additionally, alternatives were suggested for relevant prescriptions. We included 327 patients, of which ceftriaxone prescriptions were not appropriate in 37.6% of cases: 13.5% were not justified, 12.8% not relevant, and 11.3% not adapted. The main factors associated with unjustified prescriptions were urinary, dermatological, and less frequent infection sites (p < 0.001). The main factors associated with irrelevant prescriptions were patients carrying multi-resistant bacteria (p = 0.002) or already following an antibiotic prescription at emergency department admission (p = 0.024). Antibiotic prescriptions were poorly adapted in patients with a creatinine rate over 150 µmol/L (p < 0.001) and septic shocks (p = 0.032). No difference was found concerning the hospital length of stay comparing appropriate initial prescriptions to inappropriate ones. However, alternatives with lower ecological impact were suggested in 55.2% of relevant prescriptions. In emergency departments, it is crucial to preserve ceftriaxone, selecting better indications and considering alternatives.