Hydrocortisone in Severe Community-Acquired Pneumonia.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

Moderate-to-severe ARDS: COVID-19 patients compared to influenza patients for ventilator parameters and mortality.

Background: This study aimed to compare ventilatory parameters recorded in the first days of acute respiratory distress syndrome (ARDS) and mortality at day 60 between coronavirus disease 2019 (COVID-19) and influenza ARDS patients with arterial oxygen tension (P aO2 )/inspiratory oxygen fraction (F IO2 ) ≤150 mmHg. Methods: We compared 244 COVID-19 ARDS patients with 106 influenza ARDS patients. Driving pressure, respiratory system compliance (C rs), ventilator ratio, corrected minute ventilation (V'Ecorr) and surrogate of mechanical power (index=(4×driving pressure)+respiratory rate) were calculated from day 1 to day 5 of ARDS. A propensity score analysis and a principal component analysis (PCA) were performed. Results: On day 1 of ARDS, COVID-19 patients had significantly higher P aO2 /F IO2 (median (interquartile range) 97 (79-129.2) versus 83 (62.2-114) mmHg; p=0.001), and lower driving pressure (13.0 (11.0-16.0) versus 14.0 (12.0-16.7) cmH2O; p=0.01), ventilatory ratio (2.08 (1.73-2.49 versus 2.52 (1.97-3.03); p<0.001), V'Ecorr (12.7 (10.2-14.9) versus 14.9 (11.6-18.6) L·min-1; p<0.001) and index (80 (70-89) versus 84 (75-94); p=0.004). PCA demonstrated an important overlap of ventilatory parameters recorded on day 1 between the two groups. From day 1 to day 5, repeated values of P aO2 /F IO2 , arterial carbon dioxide tension, ventilatory ratio and V'Ecorr differed significantly between influenza and COVID-19 patients in the unmatched and matched populations. Mortality at day 60 did not differ significantly after matching (29% versus 21.7%; p=0.43). Conclusions: Ventilation was more impaired in influenza than in COVID-19 ARDS patients on the first day of ARDS with an important overlap of values. However, mortality at day 60 did not differ significantly in the matched population.

A Randomised trial of anti-GM-CSF Otilimab in severe COVID-19 pneumonia (OSCAR).

Abstract BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of coronavirus disease 2019 (COVID-19). METHODS: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure, and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. RESULTS: In Part 1 (N=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8, 11.4; p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2, 33.1; p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (N=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3, 11.2; p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CCL17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. CONCLUSIONS: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.

Comparison of high-flow nasal therapy, noninvasive ventilation, and continuous positive airway pressure on outcomes in critically ill patients admitted for COVID-19 with acute respiratory failure.

BACKGROUND: The optimal first-line noninvasive respiratory support (NIRS) to improve outcome in patients affected by COVID-19 pneumonia admitted to ICU is still debated. METHODS: We conducted a retrospective study in 7 French ICUs, including all adults admitted between July and December 2020 with documented SARS-CoV-2 acute respiratory failure (PaO2/FiO2 <300 mmHg), and treated with either high-flow nasal therapy (HFNT) alone, noninvasive ventilation alone or in combination with HFNT (NIV), or continuous positive airway pressure alone or in combination with HFNT (CPAP). The primary outcome was NIRS failure at day 28, defined as the need for endotracheal intubation (ETI) or death without ETI. RESULTS: Among the 355 patients included, 160 (45%) were treated with HFNT alone, 115 (32%) with NIV and 80 (23%) with CPAP. The primary outcome occurred in 65 (41%), 69 (60%), and 25 (31%) patients among those treated with HFNT alone, NIV, and CPAP, respectively (P<0.001). After univariate analysis, patients treated with CPAP had a trend for a lower incidence of the primary outcome, whereas patients treated with NIV had a significant higher incidence of the primary outcome, both compared to those treated with HFNT alone (unadjusted Hazard ratio 0.67; 95% CI [0.42-1.06], and 1.58; 95% CI [1.12-2.22]; P=0.09 and 0.008, respectively). CONCLUSIONS: Among ICU patients admitted for severe COVID-19 pneumonia and managed with NIRS, the outcome seems to differ according to the initial chosen strategy. Prospective randomized controlled studies are warranted to identify the optimal strategy.

Moderate to severe ARDS: COVID-19 patients compared to influenza patients for ventilator parameters and mortality

Background This study aimed to compare ventilatory parameters recorded the first days of ARDS, and mortality at day 60 between COVID-19 and influenza ARDS patients with PaO2/FiO2≤150 mmHg. Methods We compared 244 COVID-19 ARDS patients with 106 influenza ARDS patients. Driving pressure (DP), respiratory system compliance (CRs), ventilator ratio (VR), corrected minute ventilation (VEcorr), and surrogate of mechanical power [index=(4×DP)+respiratory rate] were calculated from day1 to day 5 of ARDS. A propensity score analysis and a principal component analysis (PCA) were performed. Results On day 1 of ARDS, COVID-19 patients had significantly higher PaO2/FiO2 ratio (median [IQR], 97 mmHg [79–129] versus 83 [62.2–114]), p=0.001), and lower DP (13 cmH20 [11–16.0] versus 14 [12.0–16.7], p=0.01), VR (2.08 [1.73–2.49 versus 2.52 [1.97–3.03], p<0.001), VEcorr (12.7 L·mn−1 [10.2–14.9] versus 14.9 [11.6–18.6], p<0.001), index (80 [70–89] versus 84 [75–94], p=0.004). PCA demonstrated an important overlap of ventilatory parameters recorded on day 1 between the two groups. From day 1 to day 5 repeated values of PaO2/FiO2 ratio, PaCO2, VR and VEcorr differed significantly between influenza and COVID-19 patients in the unmatched and matched populations. Mortality at day 60 did not differ significantly after matching (29% versus 21.7%, p=0.43). Conclusions Ventilation was more impaired in influenza than in COVID-19 ARDS patients the first day of ARDS with important overlap of values. However, mortality at day 60 did not differ significantly in the matched population. In COVID-19 and influenza patients with mild to moderate ARDS managed similarly for mechanical ventilation, dead space estimates were higher in COVID-19 patients than in influenza patients the first days of ARDS and short-term mortality similar.

Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study.

INTRODUCTION: Prognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a risk of long-term repercussions on respiratory function and neuromuscular outcomes. The functional repercussions of severe forms of COVID-19 may have a major impact on quality of life, and impair the ability to return to work or exercise. Social inequalities in healthcare may influence prognosis, with socially vulnerable individuals more likely to develop severe forms of disease. We describe here the protocol for a prospective, multicentre study that aims to investigate the influence of social vulnerability on functional recovery in patients who were hospitalised in intensive care for ARDS caused by COVID-19. This study will also include an embedded qualitative study that aims to describe facilitators and barriers to compliance with rehabilitation, describe patients' health practices and identify social representations of health, disease and care. METHODS AND ANALYSIS: The "Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status" (RECOVIDS) study is a mixed-methods, observational, multicentre cohort study performed during the routine follow-up of post-intensive care unit (ICU) functional recovery after ARDS. All patients admitted to a participating ICU for PCR-proven SARS-CoV-2 infection and who underwent chest CT scan at the initial phase AND who received respiratory support (mechanical or not) or high-flow nasal oxygen, AND had ARDS diagnosed by the Berlin criteria will be eligible. The primary outcome is the presence of lung sequelae at 6 months after ICU discharge, defined either by alterations on pulmonary function tests, oxygen desaturation during a standardised 6 min walk test or fibrosis-like pulmonary findings on chest CT. Patients will be considered to be socially disadvantaged if they have an "Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé" (EPICES) score ≥30.17 at inclusion. ETHICS AND DISSEMINATION: The study protocol and the informed consent form were approved by an independent ethics committee (Comité de Protection des Personnes Sud Méditerranée II) on 10 July 2020 (2020-A02014-35). All patients will provide informed consent before participation. Findings will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: NCT04556513.

Prone Position in COVID-19 and -COVID-19 Acute Respiratory Distress Syndrome: An International Multicenter Observational Comparative Study.

OBJECTIVES: Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 acute respiratory distress syndrome. However, it is unclear how responders may be identified and whether an oxygenation response improves outcome. The objective of this study was to quantify the response to prone position, describe the differences between coronavirus disease 2019 acute respiratory distress syndrome and acute respiratory distress syndrome, and explore variables associated with survival. DESIGN: Retrospective, observational, multicenter, international cohort study. SETTING: Seven ICUs in Italy, United Kingdom, and France. PATIENTS: Three hundred seventy-six adults (220 coronavirus disease 2019 acute respiratory distress syndrome and 156 acute respiratory distress syndrome). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Preproning, a greater proportion of coronavirus disease 2019 acute respiratory distress syndrome patients had severe disease (53% vs 40%), worse Pao2/Fio2 (13.0 kPa [interquartile range, 10.5-15.5 kPa] vs 14.1 kPa [interquartile range, 10.5-18.6 kPa]; p = 0.017) but greater compliance (38 mL/cm H2O [interquartile range, 27-53 mL/cm H2O] vs 31 mL/cm H2O [interquartile range, 21-37 mL/cm H2O]; p < 0.001). Patients with coronavirus disease 2019 acute respiratory distress syndrome had a longer median time from intubation to prone position (2.0 d [interquartile range, 0.7-5.0 d] vs 1.0 d [interquartile range, 0.5-2.9 d]; p = 0.03). The proportion of responders, defined by an increase in Pao2/Fio2 greater than or equal to 2.67 kPa (20 mm Hg), upon proning, was similar between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome (79% vs 76%; p = 0.5). Responders had earlier prone position (1.4 d [interquartile range, 0.7-4.2 d] vs 2.5 d [interquartile range, 0.8-6.2 d]; p = 0.06)]. Prone position less than 24 hours from intubation achieved greater improvement in oxygenation (11 kPa [interquartile range, 4-21 kPa] vs 7 kPa [interquartile range, 2-13 kPa]; p = 0.002). The variables independently associated with the "responder" category were Pao2/Fio2 preproning (odds ratio, 0.89 kPa-1 [95% CI, 0.85-0.93 kPa-1]; p < 0.001) and interval between intubation and proning (odds ratio, 0.94 d-1 [95% CI, 0.89-0.99 d-1]; p = 0.019). The overall mortality was 45%, with no significant difference observed between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome. Variables independently associated with mortality included age (odds ratio, 1.03 yr-1 [95% CI, 1.01-1.05 yr-1]; p < 0.001); interval between hospital admission and proning (odds ratio, 1.04 d-1 [95% CI, 1.002-1.084 d-1]; p = 0.047); and change in Pao2/Fio2 on proning (odds ratio, 0.97 kPa-1 [95% CI, 0.95-0.99 kPa-1]; p = 0.002). CONCLUSIONS: Prone position, particularly when delivered early, achieved a significant oxygenation response in ~80% of coronavirus disease 2019 acute respiratory distress syndrome, similar to acute respiratory distress syndrome. This response was independently associated with improved survival.

Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study.

BACKGROUND: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care. METHODS: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221. FINDINGS: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (>14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (<1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p<0·0001). INTERPRETATION: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19. FUNDING: Pfizer.

Open-label randomized controlled trial of ultra-low tidal ventilation without extracorporeal circulation in patients with COVID-19 pneumonia and moderate to severe ARDS: study protocol for the VT4COVID trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 pneumonia, with a mortality rate amounting to 34-50% in moderate and severe ARDS, and is associated with prolonged duration of invasive mechanical ventilation. Such as in non-COVID ARDS, harmful mechanical ventilation settings might be associated with worse outcomes. Reducing the tidal volume down to 4 mL kg-1 of predicted body weight (PBW) to provide ultra-low tidal volume ventilation (ULTV) is an appealing technique to minimize ventilator-inducted lung injury. Furthermore, in the context of a worldwide pandemic, it does not require any additional material and consumables and may be applied in low- to middle-income countries. We hypothesized that ULTV without extracorporeal circulation is a credible option to reduce COVID-19-related ARDS mortality and duration of mechanical ventilation. METHODS: The VT4COVID study is a randomized, multi-centric prospective open-labeled, controlled superiority trial. Adult patients admitted in the intensive care unit with COVID-19-related mild to severe ARDS defined by a PaO2/FiO2 ratio ≤ 150 mmHg under invasive mechanical ventilation for less than 48 h, and consent to participate to the study will be eligible. Patients will be randomized into two balanced parallels groups, at a 1:1 ratio. The control group will be ventilated with protective ventilation settings (tidal volume 6 mL kg-1 PBW), and the intervention group will be ventilated with ULTV (tidal volume 4 mL kg-1 PBW). The primary outcome is a composite score based on 90-day all-cause mortality as a prioritized criterion and the number of ventilator-free days at day 60 after inclusion. The randomization list will be stratified by site of recruitment and generated using random blocks of sizes 4 and 6. Data will be analyzed using intention-to-treat principles. DISCUSSION: The purpose of this manuscript is to provide primary publication of study protocol to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Enrollment of patients in the study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04349618 . Registered on April 16, 2020.

The eSpiro Ventilator: An Open-Source Response to a Worldwide Pandemic.

OBJECTIVE: To address the issue of ventilator shortages, our group (eSpiro Network) developed a freely replicable, open-source hardware ventilator. DESIGN: We performed a bench study. SETTING: Dedicated research room as part of an ICU affiliated to a university hospital. SUBJECTS: We set the lung model with three conditions of resistance and linear compliance for mimicking different respiratory mechanics of representative intensive care unit (ICU) patients. INTERVENTIONS: The performance of the device was tested using the ASL5000 lung model. MEASUREMENTS AND MAIN RESULTS: Twenty-seven conditions were tested. All the measurements fell within the ±10% limits for the tidal volume (VT). The volume error was influenced by the mechanical condition (p = 5.9 × 10-15) and the PEEP level (P = 1.1 × 10-12) but the clinical significance of this finding is likely meaningless (maximum -34 mL in the error). The PEEP error was not influenced by the mechanical condition (p = 0.25). Our experimental results demonstrate that the eSpiro ventilator is reliable to deliver VT and PEEP accurately in various respiratory mechanics conditions. CONCLUSIONS: We report a low-cost, easy-to-build ventilator, which is reliable to deliver VT and PEEP in passive invasive mechanical ventilation.

Effect of the use of an endotracheal tube and stylet versus an endotracheal tube alone on first-attempt intubation success: a multicentre, randomised clinical trial in 999 patients.

PURPOSE: The effect of the routine use of a stylet during tracheal intubation on first-attempt intubation success is unclear. We hypothesised that the first-attempt intubation success rate would be higher with tracheal tube + stylet than with tracheal tube alone. METHODS: In this multicentre randomised controlled trial, conducted in 32 intensive care units, we randomly assigned patients to tracheal tube + stylet or tracheal tube alone (i.e. without stylet). The primary outcome was the proportion of patients with first-attempt intubation success. The secondary outcome was the proportion of patients with complications related to tracheal intubation. Serious adverse events, i.e., traumatic injuries related to tracheal intubation, were evaluated. RESULTS: A total of 999 patients were included in the modified intention-to-treat analysis: 501 (50%) to tracheal tube + stylet and 498 (50%) to tracheal tube alone. First-attempt intubation success occurred in 392 patients (78.2%) in the tracheal tube + stylet group and in 356 (71.5%) in the tracheal tube alone group (absolute risk difference, 6.7; 95%CI 1.4-12.1; relative risk, 1.10; 95%CI 1.02-1.18; P = 0.01). A total of 194 patients (38.7%) in the tracheal tube + stylet group had complications related to tracheal intubation, as compared with 200 patients (40.2%) in the tracheal tube alone group (absolute risk difference, - 1.5; 95%CI - 7.5 to 4.6; relative risk, 0.96; 95%CI 0.83-1.12; P = 0.64). The incidence of serious adverse events was 4.0% and 3.6%, respectively (absolute risk difference, 0.4; 95%CI, - 2.0 to 2.8; relative risk, 1.10; 95%CI 0.59-2.06. P = 0.76). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, using a stylet improves first-attempt intubation success.

Mental health and stress among ICU healthcare professionals in France according to intensity of the COVID-19 epidemic.

BACKGROUND: We investigated the impact of the COVID-19 crisis on mental health of professionals working in the intensive care unit (ICU) according to the intensity of the epidemic in France. METHODS: This cross-sectional survey was conducted in 77 French hospitals from April 22 to May 13 2020. All ICU frontline healthcare workers were eligible. The primary endpoint was the mental health, assessed using the 12-item General Health Questionnaire. Sources of stress during the crisis were assessed using the Perceived Stressors in Intensive Care Units (PS-ICU) scale. Epidemic intensity was defined as high or low for each region based on publicly available data from Santé Publique France. Effects were assessed using linear mixed models, moderation and mediation analyses. RESULTS: In total, 2643 health professionals participated; 64.36% in high-intensity zones. Professionals in areas with greater epidemic intensity were at higher risk of mental health issues (p < 0.001), and higher levels of overall perceived stress (p < 0.001), compared to low-intensity zones. Factors associated with higher overall perceived stress were female sex (B = 0.13; 95% confidence interval [CI] = 0.08-0.17), having a relative at risk of COVID-19 (B = 0.14; 95%-CI = 0.09-0.18) and working in high-intensity zones (B = 0.11; 95%-CI = 0.02-0.20). Perceived stress mediated the impact of the crisis context on mental health (B = 0.23, 95%-CI = 0.05, 0.41) and the impact of stress on mental health was moderated by positive thinking, b = - 0.32, 95% CI = - 0.54, - 0.11. CONCLUSION: COVID-19 negatively impacted the mental health of ICU professionals. Professionals working in zones where the epidemic was of high intensity were significantly more affected, with higher levels of perceived stress. This study is supported by a grant from the French Ministry of Health (PHRC-COVID 2020).

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.

COVID-19 increased the risk of ICU-acquired bloodstream infections: a case-cohort study from the multicentric OUTCOMEREA network.

PURPOSE: The primary objective of this study was to investigate the risk of ICU bloodstream infection (BSI) in critically ill COVID-19 patients compared to non-COVID-19 patients. Subsequently, we performed secondary analyses in order to explain the observed results. METHODS: We conducted a matched case-cohort study, based on prospectively collected data from a large ICU cohort in France. Critically ill COVID-19 patients were matched with similar non-COVID-19 patients. ICU-BSI was defined by an infection onset occurring > 48 h after ICU admission. We estimated the effect of COVID-19 on the probability to develop an ICU-BSI using proportional subdistribution hazards models. RESULTS: We identified 321 COVID-19 patients and 1029 eligible controls in 6 ICUs. Finally, 235 COVID-19 patients were matched with 235 non-COVID-19 patients. We observed 43 ICU-BSIs, 35 (14.9%) in the COVID-19 group and 8 (3.4%) in the non-COVID-19 group (p ≤ 0.0001), respectively. ICU-BSIs of COVID-19 patients were more frequently of unknown source (47.4%). COVID-19 patients had an increased probability to develop ICU-BSI, especially after 7 days of ICU admission. Using proportional subdistribution hazards models, COVID-19 increased the daily risk to develop ICU-BSI (sHR 4.50, 95% CI 1.82-11.16, p = 0.0012). Among COVID-19 patients (n = 235), a significantly increased risk for ICU-BSI was detected in patients who received tocilizumab or anakinra (sHR 3.20, 95% CI 1.31-7.81, p = 0.011) but not corticosteroids. CONCLUSIONS: Using prospectively collected multicentric data, we showed that the ICU-BSI risk was higher for COVID-19 than non-COVID-19 critically ill patients after seven days of ICU stay. Clinicians should be particularly careful on late ICU-BSIs in COVID-19 patients. Tocilizumab or anakinra may increase the ICU-BSI risk.