Effect of intravenous almitrine on intubation or mortality in patients with COVID-19 acute hypoxemic respiratory failure: A multicentre, randomised, double-blind, placebo-controlled trial.

Background: Severe hypoxemia in patients with COVID-19 pneumonia might result from hypoxic pulmonary vasoconstriction, contributing to ventilation/perfusion (V/Q) mismatch. Because almitrine improves V/Q, it might reduce the risk for mechanical ventilation (MV) in such patients. Our primary objective was to determine the effect of almitrine on the need for MV at day 7. Methods: In a randomised double-blind placebo-controlled trial involving 15 ICUs, patients hospitalized for COVID-19 pneumonia and experiencing acute hypoxemic respiratory failure were randomly assigned to receive 5 days of intravenous low-dose (2 µg.kg-1.min-1) almitrine or placebo. The primary outcome was endotracheal intubation for MV or death within 7 days after randomisation. Secondary outcomes included in-hospital mortality, 28-day mortality, number of ventilator-free days, number of days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects. This trial was registered with ClinicalTrials.gov, NCT04357457. Findings: Between September 3, 2020 and September 25, 2021 181 patients were enrolled and randomly assigned to almitrine (n=89) or placebo (n=92). 179 patients (excluding two who withdrew from the study) were included in the intention-to-treat analysis (mean age: 60·1 years; 34% women) and analyzed. On day 7, the primary endpoint occurred in 32 patients assigned to almitrine (36%) and in 37 patients assigned to placebo (41%), for a difference of -4·3% (95% confidence interval: -18·7% to 10·2%). Secondary outcomes (28-day mortality, in-hospital mortality, ventilator-free days at day 28, days in the ICU and the hospital, and treatment discontinuation for pre-specified adverse effects) did not differ between the two groups. Interpretation: In patients with COVID-19 acute hypoxemic respiratory failure, low-dose almitrine failed in reducing the need for MV or death at day 7. Funding: Programme Hospitalier de Recherche Clinique (PHRC COVID 2020) funded by the French Ministry of Health, Les Laboratoires Servier (Suresnes, France) providing the study drug free of charge.

Comparison of Patients Infected With Delta Versus Omicron COVID-19 Variants Presenting to Paris Emergency Departments : A Retrospective Cohort Study.

BACKGROUND: At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave. OBJECTIVE: To compare baseline characteristics and in-hospital outcomes of patients with SARS-CoV-2 infection with the Delta variant versus the Omicron variant in the emergency department (ED). DESIGN: Retrospective chart reviews. SETTING: 13 adult EDs in academic hospitals in the Paris area from 29 November 2021 to 10 January 2022. PATIENTS: Patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 and variant identification. MEASUREMENTS: Main outcome measures were baseline clinical and biological characteristics at ED presentation, intensive care unit (ICU) admission, mechanical ventilation, and in-hospital mortality. RESULTS: A total of 3728 patients had a positive RT-PCR test result for SARS-CoV-2 during the study period; 1716 patients who had a variant determination (818 Delta and 898 Omicron) were included. Median age was 58 years, and 49% were women. Patients infected with the Omicron variant were younger (54 vs. 62 years; difference, 8.0 years [95% CI, 4.6 to 11.4 years]), had a lower rate of obesity (8.0% vs. 12.5%; difference, 4.5 percentage points [CI, 1.5 to 7.5 percentage points]), were more vaccinated (65% vs. 39% for 1 dose and 22% vs. 11% for 3 doses), had a lower rate of dyspnea (26% vs. 50%; difference, 23.6 percentage points [CI, 19.0 to 28.2 percentage points]), and had a higher rate of discharge home from the ED (59% vs. 37%; difference, 21.9 percentage points [-26.5 to -17.1 percentage points]). Compared with Delta, Omicron infection was independently associated with a lower risk for ICU admission (adjusted difference, 11.4 percentage points [CI, 8.4 to 14.4 percentage points]), mechanical ventilation (adjusted difference, 3.6 percentage points [CI, 1.7 to 5.6 percentage points]), and in-hospital mortality (adjusted difference, 4.2 percentage points [CI, 2.0 to 6.5 percentage points]). LIMITATION: Patients with COVID-19 illness and no SARS-CoV-2 variant determination in the ED were excluded. CONCLUSION: Compared with the Delta variant, infection with the Omicron variant in patients in the ED had different clinical and biological patterns and was associated with better in-hospital outcomes, including higher survival. PRIMARY FUNDING SOURCE: None.

Pulmonary embolism in patients with COVID-19: incidence, risk factors, clinical characteristics, and outcome.

AIMS: We investigated the incidence, risk factors, clinical characteristics, and outcomes of pulmonary embolism (PE) in patients with COVID-19 attending emergency departments (EDs), before hospitalization. METHODS AND RESULTS: We retrospectively reviewed all COVID-19 patients diagnosed with PE in 62 Spanish EDs (20% of Spanish EDs, case group) during the first COVID-19 outbreak. COVID-19 patients without PE and non-COVID-19 patients with PE were included as control groups. Adjusted comparisons for baseline characteristics, acute episode characteristics, and outcomes were made between cases and randomly selected controls (1:1 ratio). We identified 368 PE in 74 814 patients with COVID-19 attending EDs (4.92‰). The standardized incidence of PE in the COVID-19 population resulted in 310 per 100 000 person-years, significantly higher than that observed in the non-COVID-19 population [35 per 100 000 person-years; odds ratio (OR) 8.95 for PE in the COVID-19 population, 95% confidence interval (CI) 8.51-9.41]. Several characteristics in COVID-19 patients were independently associated with PE, the strongest being D-dimer >1000 ng/mL, and chest pain (direct association) and chronic heart failure (inverse association). COVID-19 patients with PE differed from non-COVID-19 patients with PE in 16 characteristics, most directly related to COVID-19 infection; remarkably, D-dimer >1000 ng/mL, leg swelling/pain, and PE risk factors were significantly less present. PE in COVID-19 patients affected smaller pulmonary arteries than in non-COVID-19 patients, although right ventricular dysfunction was similar in both groups. In-hospital mortality in cases (16.0%) was similar to COVID-19 patients without PE (16.6%; OR 0.96, 95% CI 0.65-1.42; and 11.4% in a subgroup of COVID-19 patients with PE ruled out by scanner, OR 1.48, 95% CI 0.97-2.27), but higher than in non-COVID-19 patients with PE (6.5%; OR 2.74, 95% CI 1.66-4.51). Adjustment for differences in baseline and acute episode characteristics and sensitivity analysis reported very similar associations. CONCLUSIONS: PE in COVID-19 patients at ED presentation is unusual (about 0.5%), but incidence is approximately ninefold higher than in the general (non-COVID-19) population. Moreover, risk factors and leg symptoms are less frequent, D-dimer increase is lower and emboli involve smaller pulmonary arteries. While PE probably does not increase the mortality of COVID-19 patients, mortality is higher in COVID-19 than in non-COVID-19 patients with PE.

Pulmonary embolism severity and in-hospital mortality: An international comparative study between COVID-19 and non-COVID patients.

OBJECTIVE: To compare the severity of pulmonary embolism (PE) between patients with and without COVID, and to assess the association between severity and in-hospital-mortality. METHODS: We performed an analysis of 549 COVID (71.3% PCR-confirmed) and 439 non-COVID patients with PE consecutively included by 62 Spanish and 16 French emergency departments. PE-severity was assessed by size, the presence of right ventricular dysfunction (RVD), and the sPESI. The association of PE-severity and in-hospital-mortality was assessed both in COVID and non-COVID patients, and the interaction of COVID status and PE severity/outcome associations was also evaluated. RESULTS: COVID patients had PEs of smaller size (43% vs 56% lobar or larger, 42% vs. 35% segmental and 13% vs. 9% subsegmental, respectively; p = 0.01 for trend), less RVD (22% vs. 16%, p =0.02) and lower sPESI (p =0.03 for trend). Risk of in-hospital death was higher in COVID patients (12.8% vs. 5.3%, p < 0.001). PE-severity assessed by RVD and sPESI was independently associated with in-hospital-mortality in COVID patients, while PE size and sPESI were significantly associated with in-hospital-mortality in non-COVID. COVID status showed a significant interaction in the association of PE size and outcome (p =0.01), with OR for in-hospital mortality in COVID and non-COVID patients with lobar or larger PE of 0.92 (95%CI=0.19-4.47) and 4.47 (95%CI=1.60-12.5), respectively. Sensitivity analyses using only PCR-confirmed COVID cases confirmed these results. CONCLUSION: COVID patients present a differential clinical picture, with PE of less severity than in non-COVID patients. An increased sPESI was associated with the risk of mortality in both groups but, PE size did not seem to be associated with in-hospital mortality in COVID patients.

Electrolyte imbalance in COVID-19 patients admitted to the Emergency Department: a case-control study.

In patients visiting the emergency department (ED), a potential association between electrolytes disturbance and coronavirus disease 2019 (COVID-19) has not been well studied. We aim to describe electrolyte disturbance and explore risk factors for COVID-19 infection in patients visiting the ED. We carried out a case-control study in three hospitals in France, including adult ED inpatients (≥ 18 years old). A total of 594 ED case patients in whom infection with COVID-19 was confirmed, were matched to 594 non-COVID-19 ED patients (controls) from the same period, according to sex and age. Hyponatremia was defined by a sodium of less than 135 mmol/L (reference range 135-145 mmol/L), hypokalemia by a potassium of less than 3.5 mmol/L (reference range 3.5-5.0 mmol/L), and hypochloremia by a chloride of less than 95 mmol/L (reference range 98-108 mmol/L). Among both case patients and controls, the median (IQR) age was 65 years (IQR 51-76), and 44% were women. Hyponatremia was more common among case patients than among controls, as was hypokalemia and hypochloremia. Based on the results of the multivariate logistic regression, hyponatremia, and hypokalemia were associated with COVID-19 among case patients overall, with an adjusted odds ratio of 1.89 [95% CI 1.24-2.89] for hyponatremia and 1.76 [95% CI 1.20-2.60] for hypokalemia. Hyponatremia and hypokalemia are independently associated with COVID-19 infection in adults visiting the ED, and could act as surrogate biomarkers for the emergency physician in suspected COVID-19 patients.

Diagnostic performance of chest computed tomography during the epidemic wave of COVID-19 varied as a function of time since the beginning of the confinement in France.

OBJECTIVE: To evaluate the diagnostic performance of the initial chest CT to diagnose COVID-19 related pneumonia in a French population of patients with respiratory symptoms according to the time from the onset of country-wide confinement to better understand what could be the role of the chest CT in the different phases of the epidemic. MATERIAL AND METHOD: Initial chest CT of 1064 patients with respiratory symptoms suspect of COVID-19 referred between March 18th, and May 12th 2020, were read according to a standardized procedure. The results of chest CTs were compared to the results of the RT-PCR. RESULTS: 546 (51%) patients were found to be positive for SARS-CoV2 at RT-PCR. The highest rate of positive RT-PCR was during the second week of confinement reaching 71.9%. After six weeks of confinement, the positive RT-PCR rate dropped significantly to 10.5% (p<0.001) and even 2.2% during the two last weeks. Overall, CT revealed patterns suggestive of COVID-19 in 603 patients (57%), whereas an alternative diagnosis was found in 246 patients (23%). CT was considered normal in 215 patients (20%) and inconclusive in 1 patient. The overall sensitivity of CT was 88%, specificity 76%, PPV 79%, and NPV 85%. At week-2, the same figures were 89%, 69%, 88% and 71% respectively and 60%, 84%, 30% and 95% respectively at week-6. At the end of confinement when the rate of positive PCR became extremely low the sensitivity, specificity, PPV and NPV of CT were 50%, 82%, 6% and 99% respectively. CONCLUSION: At the peak of the epidemic, chest CT had sufficiently high sensitivity and PPV to serve as a first-line positive diagnostic tool but at the end of the epidemic wave CT is more useful to exclude COVID-19 pneumonia.

Association Between Pulmonary Embolism and COVID-19 in Emergency Department Patients Undergoing Computed Tomography Pulmonary Angiogram: The PEPCOV International Retrospective Study.

BACKGROUND: There have been reports of procoagulant activity in patients with COVID-19. Whether there is an association between pulmonary embolism (PE) and COVID-19 in the emergency department (ED) is unknown. The aim of this study was to assess whether COVID-19 is associated with PE in ED patients who underwent a computed tomographic pulmonary angiogram (CTPA). METHODS: A retrospective study in 26 EDs from six countries. ED patients in whom a CTPA was performed for suspected PE during a 2-month period covering the pandemic peak. The primary endpoint was the occurrence of a PE on CTPA. COVID-19 was diagnosed in the ED either on CT or reverse transcriptase-polymerase chain reaction. A multivariable binary logistic regression was built to adjust with other variables known to be associated with PE. A sensitivity analysis was performed in patients included during the pandemic period. RESULTS: A total of 3,358 patients were included, of whom 105 were excluded because COVID-19 status was unknown, leaving 3,253 for analysis. Among them, 974 (30%) were diagnosed with COVID-19. Mean (±SD) age was 61 (±19) years and 52% were women. A PE was diagnosed on CTPA in 500 patients (15%). The risk of PE was similar between COVID-19 patients and others (15% in both groups). In the multivariable binary logistic regression model, COVID-19 was not associated with higher risk of PE (adjusted odds ratio = 0.98, 95% confidence interval = 0.76 to 1.26). There was no association when limited to patients in the pandemic period. CONCLUSION: In ED patients who underwent CTPA for suspected PE, COVID-19 was not associated with an increased probability of PE diagnosis. These results were also valid when limited to the pandemic period. However, these results may not apply to patients with suspected COVID-19 in general.