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OBJECTIVES: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. DESIGN: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. SETTING: Twelve clinical sites in France (ICU and general hospitals). PATIENTS: Patients receiving greater than or equal to 5 L oxygen/min to maintain Spo2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. MEASUREMENTS AND MAIN RESULTS: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of –0.26 (95% CI, –1.2 to 0.7; p = 0.7) in cohort 1 and –0.28 (95% CI, –1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of –6.3 (95% CI, –13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. CONCLUSIONS: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367).

Introduction: This study investigated invasive mechanical ventilation modalities used in severe blunt chest trauma patients with pulmonary contusion. Occurrence, risk factors, and outcomes of early onset acute respiratory distress syndrome were also evaluated. Methods: We performed a retrospective multicenter observational study including 115 adult patients hospitalized in six level 1 trauma intensive care units between April and September of 2014. Independent predictors of early onset acute respiratory distress syndrome were determined by multiple logistic regression analysis based on clinical characteristics and initial management. Results: Protective ventilation principles were highly implemented, even prophylactically before acute respiratory distress syndrome occurrence. Early onset acute respiratory distress syndrome appeared to be associated with lung contusion of >20% of total lung volume and early onset pneumonia. Conclusions: Predictors of early onset acute respiratory distress syndrome could help with identifying high-risk populations, potentially improving case management through specific protocol development for these patients.

Rhabdomyolysis is a frequent disorder in EVD and seems to be more common than in other viral infections. It may contribute to the renal failure observed in nonsurviving patients. More studies are needed to determine the impact of rhabdomyolysis on EVD outcome.

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Background We designed an algorithm to assess COVID-19 patients severity and dynamic intubation needs and predict their length of stay using the breathing frequency (BF) and oxygen saturation (SpO 2 ) signals. Methods We recorded the BF and SpO 2 signals for confirmed COVID-19 patients admitted to the ICU of a teaching hospital during both the first and subsequent outbreaks of the pandemic in France. An unsupervised machine-learning algorithm (the Gaussian mixture model) was applied to the patients' data for clustering. The algorithm's robustness was ensured by comparing its results against actual intubation rates. We predicted intubation rates using the algorithm every hour, thus conducting a severity evaluation. We designed a S 24 severity score that represented the patient's severity over the previous 24 h; the validity of MS 24 , the maximum S 24 score, was checked against rates of intubation risk and prolonged ICU stay. Results Our sample included 279 patients. . The unsupervised clustering had an accuracy rate of 87.8% for intubation recognition (AUC = 0.94, True Positive Rate 86.5%, true Negative Rate 90.9%). The S 24 score of intubated patients was significantly higher than that of non-intubated patients at 48 h before intubation. The MS 24 score allowed for the distinguishing between three severity levels with an increased risk of intubation: green (3.4%), orange (37%), and red (77%). A MS 24 score over 40 was highly predictive of an ICU stay greater than 5 days at an accuracy rate of 81.0% (AUC = 0.87). Conclusions Our algorithm uses simple signals and seems to efficiently visualize the patients' respiratory situations, meaning that it has the potential to assist staffs' in decision-making. Additionally, real-time computation is easy to implement.

This study demonstrated the impact of fluid resuscitation on contused lungs. Twenty hours after the trauma, all three resuscitation approaches showed modest clinical consequences, with moderate lung edema and reduced compliance in response to the infused volume.

Aim: Describing acute respiratory distress syndrome patterns, therapeutics management, and outcomes of ICU COVID-19 patients and to determine risk factors of 28-day mortality. Methods: Prospective multicentre, cohort study conducted in 29 French ICUs. Baseline characteristics, comorbidities, adjunctive therapies, ventilatory support at ICU admission and survival data were collected. Results: From March to July 2020, 966 patients were enrolled with a median age of 66 (interquartile range 58-73) years and a median SAPS II of 37 (29-48). On the first 24 hours of ICU admission, COVID-19 patients received one of the following respiratory supports: mechanical ventilation for 559 (58%), standard oxygen therapy for 228 (24%) and high-flow nasal cannula (HFNC) for 179 (19%) patients. Overall, 721 (75%) patients were mechanically ventilated during their ICU stay. Prone positioning and neuromuscular blocking agents were used in 494 (51%) and 460 (48%) patients, respectively. Bacterial co-infections and ventilator-associated pneumonia were diagnosed in 79 (3%) and 411 (43%) patients, respectively. The overall 28-day mortality was 18%. Age, pre-existing comorbidities, severity of respiratory failure and the absence of antiviral therapy on admission were identified as independent predictors of 28-day outcome. Conclusion: Severity of hypoxaemia on admission, older age (> 70 years), cardiovascular and renal comorbidities were associated with worse outcome in COVID-19 patients. Antiviral treatment on admission was identified as a protective factor for 28-day mortality. Characterising the determinants of outcomes of critically ill COVID-19 patients is crucial to optimise hospital and ICU resources and to provide the appropriate intensity level of care.