Physiologic Effects of the Awake Prone Position Combined With High-Flow Nasal Oxygen on Gas Exchange and Work of Breathing in Patients With Severe COVID-19 Pneumonia: A Randomized Crossover Trial.

To determine the effect of the awake prone position (APP) on gas exchange and the work of breathing in spontaneously breathing patients with COVID-19-associated acute hypoxemic respiratory failure (AHRF) supported by high-flow nasal oxygen. DESIGN: Prospective randomized physiologic crossover multicenter trial. SETTINGS: Four ICUs in Marseille, France. PATIENTS: Seventeen patients with laboratory-confirmed COVID-19 pneumonia and Pao2/Fio2 less than or equal to 300 mm Hg while treated with high-flow nasal cannula oxygen therapy. INTERVENTIONS: Periods of APP and semirecumbent position (SRP) were randomly applied for 2 hours and separated by a 2-hour washout period. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases, end-tidal CO2. and esophageal pressure were recorded prior to and at the end of each period. Inspiratory muscle effort was assessed by measuring the esophageal pressure swing (∆PES) and the simplified esophageal pressure-time product (sPTPES). The other endpoints included physiologic dead space to tidal volume ratio (VD/VT) and the transpulmonary pressure swing. The APP increased the Pao2/Fio2 from 84 Torr (61-137 Torr) to 208 Torr (114-226 Torr) (p = 0.0007) and decreased both the VD/VT and the respiratory rate from 0.54 (0.47-0.57) to 0.49 (0.45-0.53) (p = 0.012) and from 26 breaths/min (21-30 breaths/min) to 21 breaths/min (19-22 breaths/min), respectively (p = 0.002). These variables remained unchanged during the SRP. The ∆PES and sPTPES per breath were unaffected by the position. However, the APP reduced the sPTPES per minute from 225 cm H2O.s.m-1 (176-332 cm H2O.s.m-1) to 174 cm H2O.s.m-1 (161-254 cm H2O.s.m-1) (p = 0.049). CONCLUSIONS: In spontaneously breathing patients with COVID-19-associated AHRF supported by high-flow nasal oxygen, the APP improves oxygenation and reduces the physiologic dead space, respiratory rate, and work of breathing per minute.

Ventilator Acquired Pneumonia in COVID-19 ICU Patients: A Retrospective Cohort Study during Pandemia in France.

Describe the characteristics of ventilation-acquired pneumonia (VAP) and potential risk factors in critically ill SARS-CoV-2 patients admitted in three French public hospitals during the first year of the COVID-19 pandemic. We conducted a monocentric retrospective study in seven Marseille intensive care units (ICUs) aiming to describe VAP characteristics and identify their risk factors. VAP patients were compared to a non-VAP control group. From March to November 2020, 161 patients admitted for viral-induced acute respiratory failure (ARF) requiring invasive mechanical ventilation (IMV) were included. This cohort was categorized in two groups according to the development or not of a VAP during their stay in ICU. 82 patients (51%) developed ventilation-acquired pneumonia. Most of them were men (77%) and 55% had hypertension. In the VAP population, 31 out of 82 patients (38%) had received dexamethasone and 47% were administered antibiotic course prior to ICU admission. An amount of 88% of respiratory infections were late VAPs with a median delay of 10 days from the onset of IMV. Gram negative bacteria were responsible for 62% of VAPs with Pseudomonas spp. being the most documented bacteria. Less than a third of the ICU-acquired infections were due to multidrug resistant (MDR) bacteria mainly displaying AmpC cephalosporin hyper production resistance phenotype. Multivariate analysis revealed that early Dexamethasone administration in ICU, male sex, older age and ROX score were risk factors for VAP whereas pre-ICU antimicrobial treatment and higher IGS 2 were protective factors. VAP is a frequent ICU-related complication affecting half of patients infected with SARS-CoV-2 and requiring IMV. It was responsible for increased morbidity due to a longer ICU and hospital stay. VAP risk factors included demographic factors such as age and sex. Dexamethasone was associated with a threefold greater risk of developing VAP during ICU stay. These results need to be comforted by large multi-centric studies before questioning the only available and effective treatment against SARS-CoV-2 in ICU patients.

Prevalence of COVID-Associated Renal Injury in ICU and Prognosis of Proximal Tubular Dysfunction in Acute Respiratory Distress Syndrome

BACKGROUND AND AIMS During COVID-19, the renal impairment is the most frequent after lung impairment and is associated of poor prognosis particularly in the intensive care unit (ICU). In this work, we aim to assess the incidence of acute kidney injury (AKI) in COVID-19-related acute respiratory distress syndrome (ARDS) patients, the existence of an early renal dysfunction and its prognosis, and its specificity compared with patients with non-COVID ARDS. METHOD This a prospective and multicentric study led in four ICUs. Patients of 18 years and older in ICU with invasive mechanical ventilation for ARDS were enrolled. Precise evaluation of renal dysfunction markers, including urinary protein electrophoresis, was performed within 24 h after the onset of mechanical ventilation. RESULTS From March 2020 to September 2021, 131 patients in ICU for ARDS were enrolled, 98 COVID-19 ARDS and 33 ARDS from other causes. There was more tubular profile in COVID-19 patients (68% versus 24%;P = .001) and a more mixed, tubular and glomerular profile in non-COVID-19 patients (29% versus 14%;P = .001). COVID-19 patients displayed an important tubular proteinuria, tended to display more AKI (49% versus 31%;P = .07), and had a longer duration of mechanical ventilation (18 versus 10 days;P = .002) and longer ICU length of stay (23 versus 15 days;P = .013). In COVID-19 patients, tubular proteinuria was associated with poor renal prognosis with a significant association with the onset of KDIGO ≥ 2 AKI. CONCLUSION COVID-19 ARDS patients had a specific renal impairment with tubular dysfunction, which appeared to be of poor prognosis on kidney and disease evolution.

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.

High-flow oxygen therapy in elderly patients infected with SARS-CoV2 with a contraindication for transfer to an intensive care unit: A preliminary report.

OBJECTIVES: In a conventional hospital ward, we used high-flow nasal oxygen (HFNO) to treat elderly COVID-19 patients noneligible for intensive care unit transfer. METHODS: This study was conducted in the Institut Hospitalo-Universitaire Méditerranée Infection, Assistance Publique-Hôpitaux de Marseille (AP-HM), France. We used high-flow nasal oxygen (HFNO) in our conventional infectious disease ward from 15 September 2020 for elderly patients noneligible for intensive care unit transfer. RESULTS: Of the 44 patients (median age 83 years (57-94), mean: 80.25), 61.4% (27/44) were men. The median Charlson score was 7 (1-15). The median of the NEWS-2 score upon admission was 8 (3-11) and was 10 at the time of initiation of HFNO. The median PaO2/FiO2 ratio was 103 (71-151) prior to HNFO initiation. Among the 44 patients, 16 patients (36.4%) had been weaned from HFNO, and 28 patients had died (63.6%). CONCLUSIONS: In this preliminary report, we observed that HFNO saved the lives of one-third of elderly COVID-19 patients who would have systematically died.

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.

Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis.

Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic1. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes1. Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a-C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a-C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19.