Rationale Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid therapy. Objectives To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP). Methods We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics. Measurements and main results Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio [aHR] 1.29; 95% confidence interval [95% CI] 1.05–1.58; P = 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58–1.53; P = 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83–1.60; P = 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33–2.61; P = 0.0003). Conclusions Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.

Background Dexamethasone is recommended for COVID-19 patients who require oxygen therapy. However, its effectiveness in reducing mortality and intubation, and its safety, remain debated. We aimed to investigate whether dexamethasone reduces day-28 mortality in unselected patients with critical COVID-19. Methods We performed an observational cohort study in consecutive COVID-19 patients admitted to any of 13 French intensive care units (ICUs) in 2020. The primary objective was to determine whether early dexamethasone therapy was associated with day-28 mortality and the secondary objectives were to assess whether early dexamethasone decreased intubation requirements and to collect adverse events. Results Of 1058 included patients, 611 (57.75%) received early dexamethasone (early dexamethasone group), 358 (33.83%) did not receive any steroids (no steroids group), and 89 (8.41%) received late dexamethasone or other steroids. Day-28 mortality was similar between the early dexamethasone and the no steroids groups (15.06% and 14.25%, respectively; P = 0.59). Factors associated with day-28 mortality were older age (adjusted hazard ratio [aHR], 1.06; 1.04–1.09; P < 0.001), worse SOFA score (aHR, 1.13; 1.06–1.20; P < 0.001), and immunocompromised status (aHR, 1.59; 1.01–2.50; P = 0.043). Early dexamethasone was associated with fewer intubations (48.55% vs. 61.49%, P < 0.001) and more ventilator-free days by day 28 (22 [2–28] vs. 17 [1–28] days, P = 0.003), compared to no steroids. Ventilator-associated pneumonia (VAP) was more common with early dexamethasone (HR, 1.29 [1.01–1.63], P = 0.04) than with no steroids, whereas no differences were noted for bloodstream infection, fungal infection, or gastrointestinal bleeding. Conclusions Early dexamethasone in critically ill COVID-19 patients was not associated with lower day-28 mortality. However, early dexamethasone was associated with lower intubation needs and more ventilator-free days by day 28. In patients treated with invasive mechanical ventilation, early dexamethasone was associated with a higher risk of VAP.

Immunocompromised subjects are at risk of severe viral infections which may require intensive care unit (ICU) admission. Data on the outcome of influenza pneumonia in critically-ill immunocompromised subjects are limited. We conducted a single-center observational study. All subjects admitted to the ICU for influenza pneumonia between 2016 and 2020 were included. The main objective was to compare the clinical features and outcome of critically-ill subjects with flu according to their immune status. 137 subjects (age 60 years-old, 58.4% male) were included, of whom 58 (42.34%) were intubated during the ICU stay. Fortythree (31.4%) subjects were immunocompromised. Immunocompromised subjects had a higher Charlson comorbidity index. In contrast, severity scores and hypoxemia at ICU admission, and ventilatory support during ICU stay were similar between the 2 groups. There was no difference in the rate of co-infections and ventilator-associated pneumonia between the 2 groups. Among intubated subjects, 10 (23.26%) immunocompromised subjects developed severe acute respiratory distress syndrome compared to 13 (13.83%) non-immunocompromised (P = .218). ICU mortality was 13.97%, with mortality being 3-times higher in immunocompromised subjects (25.58% vs 8.6%, P = .015). On multivariable analysis, immunocompromised status, higher age and lower arterial oxygen partial pressure/fraction of inspired oxygen were associated with an increased ICU mortality. Immunocompromised subjects with severe influenza pneumonia were more likely to develop severe acute respiratory distress syndrome and had a 3-fold increase in ICU mortality compared to non-immunocompromised subjects. Such difference was not explained by an increased rate of co-infections or nosocomial pneumonia, suggesting that influenza virus was by itself responsible of a more severe form of pulmonary disease in immunocompromised subjects.Abbreviations: ARDS = acute respiratory distress syndrome, FiO 2 = fraction of inspired oxygen, ICD-10 = international classification of diseases 10th revision, ICU = intensive care unit, MV = mechanical ventilation, PaO 2 = arterial oxygen partial pressure, VAP = ventilator-associated pneumonia.

Background Patients with critical illness due to COVID-19 exhibit increased coagulability associated with a high risk of venous thrombo-embolism (VTE). Data on prophylactic anticoagulation for these patients are limited and conflicting. The purpose of this study was to evaluate whether intermediate-dose prophylactic anticoagulation in patients with COVID-19 requiring ICU admission was associated with better outcomes compared to standard-dose prophylactic anticoagulation. Methods We retrospectively included adults admitted with severe COVID-19 to any of 15 ICUs, in 2020 or 2021. We compared the groups given intermediate-dose vs. standard-dose prophylactic anticoagulation. The primary outcome was all-cause day-90 mortality. Secondary outcomes were VTE (pulmonary embolism or deep vein thrombosis), ICU stay length, and adverse effects of anticoagulation. Results Of 1174 included patients (mean age, 63 years), 399 received standard-dose and 775 intermediate-dose prophylactic anticoagulation. Of the 211 patients who died within 90 days, 86 (21%) received intermediate and 125 (16%) standard doses. After adjustment on early corticosteroid therapy and critical illness severity, there were no significant between-group differences in day-90 mortality (hazard ratio [HR], 0.73; 95%CI, 0.52–1.04; p = 0.09) or ICU stay length (HR, 0.93; 95%CI, 0.79–1.10; p = 0.38). Intermediate-dose anticoagulation was significantly associated with fewer VTE events (HR, 0.55; 95%CI, 0.38–0.80; p < 0.001). Bleeding events occurred in similar proportions of patients in the two groups (odds ratio, 0.86; 95%CI, 0.50–1.47; p = 0.57). Conclusions Mortality on day 90 did not differ between the groups given standard-dose and intermediate-dose prophylactic anticoagulation, despite a higher incidence of VTE in the standard-dose group.

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