Unchanged Characteristics and Survival among Critically Ill COVID-19 Patients during First, Second, and Third Waves: A Prospective Observational Cohort.

BACKGROUND: This study was carried out to compare characteristics and outcomes in patients with acute respiratory failure related to COVID-19 during first, second, and third waves. METHODS: We included consecutive adults admitted to the intensive care unit between March 2020 and July 2021. We compared three groups defined by the epidemic intake phase: waves 1 (W1), 2 (W2), and 3 (W3). RESULTS: We included 289 patients. Two hundred and eight (72%) patients were men with a median age of 63 years (IQR: 54-72), of whom 68 (23.6%) died in hospital. High-flow nasal oxygen (HFNO) was inversely associated with the need for invasive mechanical ventilation (MV) in multivariate analysis (p = 0.003) but not dexamethasone (p = 0.25). The day-90 mortality rate did not vary from W1 (27.4%) to W2 (23.9%) and W3 (22%), p = 0.67. By multivariate analysis, older age (odds ratio [OR]: 0.94/year, p < 0.001), immunodeficiency (OR: 0.33, p = 0.04), acute kidney injury (OR: 0.26, p < 0.001), and invasive MV (OR: 0.13, p < 0.001) were inversely associated with higher day-90 survival as opposed to the use of intermediate heparin thromboprophylaxis dose (OR: 3.21, p = 0.006). HFNO use and dexamethasone were not associated with higher day-90 survival (p = 0.24 and p = 0.56, respectively). CONCLUSIONS: In patients with acute respiratory failure due to COVID-19, survival did not change between first, second, and third waves while the use of invasive MV decreased. HFNO or intravenous steroids were not associated with better outcomes, whereas the use of intermediate dose of heparin for thromboprophylaxis was associated with higher day-90 survival. Larger multicentric studies are needed to confirm our findings.

Ventilator-Associated Pneumonia in COVID-19 Patients Admitted in Intensive Care Units: Relapse, Therapeutic Failure and Attributable Mortality-A Multicentric Observational Study from the OutcomeRea Network.

Introduction: Ventilator-associated pneumonia (VAP) incidence is high among critically ill COVID-19 patients. Its attributable mortality remains underestimated, especially for unresolved episodes. Indeed, the impact of therapeutic failures and the determinants that potentially affect mortality are poorly evaluated. We assessed the prognosis of VAP in severe COVID-19 cases and the impact of relapse, superinfection, and treatment failure on 60-day mortality. Methods: We evaluated the incidence of VAP in a multicenter prospective cohort that included adult patients with severe COVID-19, who required mechanical ventilation for ≥48 h between March 2020 and June 2021. We investigated the risk factors for 30-day and 60-day mortality, and the factors associated with relapse, superinfection, and treatment failure. Results: Among 1424 patients admitted to eleven centers, 540 were invasively ventilated for 48 h or more, and 231 had VAP episodes, which were caused by Enterobacterales (49.8%), P. aeruginosa (24.8%), and S. aureus (22%). The VAP incidence rate was 45.6/1000 ventilator days, and the cumulative incidence at Day 30 was 60%. VAP increased the duration of mechanical ventilation without modifying the crude 60-day death rate (47.6% vs. 44.7% without VAP) and resulted in a 36% increase in death hazard. Late-onset pneumonia represented 179 episodes (78.2%) and was responsible for a 56% increase in death hazard. The cumulative incidence rates of relapse and superinfection were 45% and 39.5%, respectively, but did not impact death hazard. Superinfection was more frequently related to ECMO and first episode of VAP caused by non-fermenting bacteria. The risk factors for treatment failure were an absence of highly susceptible microorganisms and vasopressor need at VAP onset. Conclusions: The incidence of VAP, mainly late-onset episodes, is high in COVID-19 patients and associated with an increased risk of death, similar to that observed in other mechanically ventilated patients. The high rate of VAP due to difficult-to-treat microorganisms, pharmacokinetic alterations induced by renal replacement therapy, shock, and ECMO likely explains the high cumulative risk of relapse, superinfection, and treatment failure.

Bacterial Pulmonary Co-Infections on ICU Admission: Comparison in Patients with SARS-CoV-2 and Influenza Acute Respiratory Failure: A Multicentre Cohort Study.

BACKGROUND: Few data are available on the impact of bacterial pulmonary co-infection (RespCoBact) during COVID-19 (CovRespCoBact). The aim of this study was to compare the prognosis of patients admitted to an ICU for influenza pneumonia and for SARS-CoV-2 pneumonia with and without RespCoBact. METHODS: This was a multicentre (n = 11) observational study using the Outcomerea© database. Since 2008, all patients admitted with influenza pneumonia or SARS-CoV-2 pneumonia and discharged before 30 June 2021 were included. Risk factors for day-60 death and for ventilator-associated-pneumonia (VAP) in patients with influenza pneumonia or SARS-CoV-2 pneumonia with or without RespCoBact were determined. RESULTS: Of the 1349 patients included, 157 were admitted for influenza and 1192 for SARS-CoV-2. Compared with the influenza patients, those with SARS-CoV-2 had lower severity scores, were more often under high-flow nasal cannula, were less often under invasive mechanical ventilation, and had less RespCoBact (8.2% for SARS-CoV-2 versus 24.8% for influenza). Day-60 death was significantly higher in patients with SARS-CoV-2 pneumonia with no increased risk of mortality with RespCoBact. Patients with influenza pneumonia and those with SARS-CoV-2 pneumonia had no increased risk of VAP with RespCoBact. CONCLUSIONS: SARS-CoV-2 pneumonia was associated with an increased risk of mortality compared with Influenza pneumonia. Bacterial pulmonary co-infections on admission were not associated with patient survival rates nor with an increased risk of VAP.

Association of ventilator type with hospital mortality in critically ill patients with SARS-CoV2 infection: a prospective study.

BACKGROUND: To evaluate the association between ventilator type and hospital mortality in patients with acute respiratory distress syndrome (ARDS) related to COVID-19 (SARS-CoV2 infection), a single-center prospective observational study in France. RESULTS: We prospectively included consecutive adults admitted to the intensive care unit (ICU) of a university-affiliated tertiary hospital for ARDS related to proven COVID-19, between March 2020 and July 2021. All patients were intubated. We compared two patient groups defined by whether an ICU ventilator or a less sophisticated ventilator such as a sophisticated turbine-based transport ventilator was used. Kaplan-Meier survival curves were plotted. Cox multivariate regression was performed to identify associations between patient characteristics and hospital mortality. We included 189 patients (140 [74.1%] men) with a median age of 65 years [IQR, 55-73], of whom 61 (32.3%) died before hospital discharge. By multivariate analysis, factors associated with in-hospital mortality were age ≥ 70 years (HR, 2.11; 95% CI, 1.24-3.59; P = 0.006), immunodeficiency (HR, 2.43; 95% CI, 1.16-5.09; P = 0.02) and serum creatinine ≥ 100 µmol/L (HR, 3.01; 95% CI, 1.77-5.10; P < 0.001) but not ventilator type. As compared to conventional ICU (equipped with ICU and anesthesiology ventilators), management in transient ICU (equipped with non-ICU turbine-based ventilators) was associated neither with a longer duration of invasive mechanical ventilation (18 [IQR, 11-32] vs. 21 [13-37] days, respectively; P = 0.39) nor with a longer ICU stay (24 [IQR, 14-40] vs. 27 [15-44] days, respectively; P = 0.44). CONCLUSIONS: In ventilated patients with ARDS due to COVID-19, management in transient ICU equipped with non-ICU sophisticated turbine-based ventilators was not associated with worse outcomes compared to standard ICU, equipped with ICU ventilators. Although our study design is not powered to demonstrate any difference in outcome, our results after adjustment do not suggest any signal of harm when using these transport type ventilators as an alternative to ICU ventilators during COVID-19 surge.

Impact of early corticosteroids on 60-day mortality in critically ill patients with COVID-19: A multicenter cohort study of the OUTCOMEREA network.

OBJECTIVES: In severe COVID-19 pneumonia, the appropriate timing and dosing of corticosteroids (CS) is not known. Patient subgroups for which CS could be more beneficial also need appraisal. The aim of this study was to assess the effect of early CS in COVID-19 pneumonia patients admitted to the ICU on the occurrence of 60-day mortality, ICU-acquired-bloodstream infections(ICU-BSI), and hospital-acquired pneumonia and ventilator-associated pneumonia(HAP-VAP). METHODS: We included patients with COVID-19 pneumonia admitted to 11 ICUs belonging to the French OutcomeReaTM network from January to May 2020. We used survival models with ponderation with inverse probability of treatment weighting (IPTW). RESULTS: The study population comprised 303 patients having a median age of 61.6 (53-70) years of whom 78.8% were male and 58.6% had at least one comorbidity. The median SAPS II was 33 (25-44). Invasive mechanical ventilation was required in 34.8% of the patients. Sixty-six (21.8%) patients were in the Early-C subgroup. Overall, 60-day mortality was 29.4%. The risks of 60-day mortality (IPTWHR = 0.86;95% CI 0.54 to 1.35, p = 0.51), ICU-BSI and HAP-VAP were similar in the two groups. Importantly, early CS treatment was associated with a lower mortality rate in patients aged 60 years or more (IPTWHR, 0.53;95% CI, 0.3-0.93; p = 0.03). In contrast, CS was associated with an increased risk of death in patients younger than 60 years without inflammation on admission (IPTWHR = 5.01;95% CI, 1.05, 23.88; p = 0.04). CONCLUSION: For patients with COVID-19 pneumonia, early CS treatment was not associated with patient survival. Interestingly, inflammation and age can significantly influence the effect of CS.

Multistate Modeling of COVID-19 Patients Using a Large Multicentric Prospective Cohort of Critically Ill Patients.

The mortality of COVID-19 patients in the intensive care unit (ICU) is influenced by their state at admission. We aimed to model COVID-19 acute respiratory distress syndrome state transitions from ICU admission to day 60 outcome and to evaluate possible prognostic factors. We analyzed a prospective French database that includes critically ill COVID-19 patients. A six-state multistate model was built and 17 transitions were analyzed either using a non-parametric approach or a Cox proportional hazard model. Corticosteroids and IL-antagonists (tocilizumab and anakinra) effects were evaluated using G-computation. We included 382 patients in the analysis: 243 patients were admitted to the ICU with non-invasive ventilation, 116 with invasive mechanical ventilation, and 23 with extracorporeal membrane oxygenation. The predicted 60-day mortality was 25.9% (95% CI: 21.8%-30.0%), 44.7% (95% CI: 48.8%-50.6%), and 59.2% (95% CI: 49.4%-69.0%) for a patient admitted in these three states, respectively. Corticosteroids decreased the risk of being invasively ventilated (hazard ratio (HR) 0.59, 95% CI: 0.39-0.90) and IL-antagonists increased the probability of being successfully extubated (HR 1.8, 95% CI: 1.02-3.17). Antiviral drugs did not impact any transition. In conclusion, we observed that the day-60 outcome in COVID-19 patients is highly dependent on the first ventilation state upon ICU admission. Moreover, we illustrated that corticosteroid and IL-antagonists may influence the intubation duration.

Association Between Early Invasive Mechanical Ventilation and Day-60 Mortality in Acute Hypoxemic Respiratory Failure Related to Coronavirus Disease-2019 Pneumonia.

OBJECTIVES: About 5% of patients with coronavirus disease-2019 are admitted to the ICU for acute hypoxemic respiratory failure. Opinions differ on whether invasive mechanical ventilation should be used as first-line therapy over noninvasive oxygen support. The aim of the study was to assess the effect of early invasive mechanical ventilation in coronavirus disease-2019 with acute hypoxemic respiratory failure on day-60 mortality. DESIGN: Multicenter prospective French observational study. SETTING: Eleven ICUs of the French OutcomeRea network. PATIENTS: Coronavirus disease-2019 patients with acute hypoxemic respiratory failure (Pao2/Fio2 ≤ 300 mm Hg), without shock or neurologic failure on ICU admission, and not referred from another ICU or intermediate care unit were included. INTERVENTION: We compared day-60 mortality in patients who were on invasive mechanical ventilation within the first 2 calendar days of the ICU stay (early invasive mechanical ventilation group) and those who were not (nonearly invasive mechanical ventilation group). We used a Cox proportional-hazard model weighted by inverse probability of early invasive mechanical ventilation to determine the risk of death at day 60. MEASUREMENT AND MAIN RESULTS: The 245 patients included had a median (interquartile range) age of 61 years (52-69 yr), a Simplified Acute Physiology Score II score of 34 mm Hg (26-44 mm Hg), and a Pao2/Fio2 of 121 mm Hg (90-174 mm Hg). The rates of ICU-acquired pneumonia, bacteremia, and the ICU length of stay were significantly higher in the early (n = 117 [48%]) than in the nonearly invasive mechanical ventilation group (n = 128 [52%]), p < 0.01. Day-60 mortality was 42.7% and 21.9% in the early and nonearly invasive mechanical ventilation groups, respectively. The weighted model showed that early invasive mechanical ventilation increased the risk for day-60 mortality (weighted hazard ratio =1.74; 95% CI, 1.07-2.83, p=0.03). CONCLUSIONS: In ICU patients admitted with coronavirus disease-2019-induced acute hypoxemic respiratory failure, early invasive mechanical ventilation was associated with an increased risk of day-60 mortality. This result needs to be confirmed.