SARS-CoV-2 variants and mutational patterns: relationship with risk of ventilator-associated pneumonia in critically ill COVID-19 patients in the era of dexamethasone.

We aimed to explore the relationships between specific viral mutations/mutational patterns and ventilator-associated pneumonia (VAP) occurrence in COVID-19 patients admitted in intensive care units between October 1, 2020, and May 30, 2021. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing. In this prospective multicentre cohort study, 259 patients were included. 222 patients (47%) had been infected with pre-existing ancestral variants, 116 (45%) with variant α, and 21 (8%) with other variants. 153 patients (59%) developed at least one VAP. There was no significant relationship between VAP occurrence and a specific SARS CoV-2 lineage/sublineage or mutational pattern.

Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia: The ANTICOVID Randomized Clinical Trial.

Importance: Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative. Objectives: To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies. Design, Settings, and Participants: The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023. Interventions: Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days. Main Outcomes and Measures: A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death). Results: Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95% CI -6.2 to -23.2] and -14.7 [95% CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95% CI -2.6 to -24.3). Conclusions and Relevance: This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04808882.

Acute Kidney Injury in Critically-Ill COVID-19 Patients.

PURPOSE: Acute kidney injury (AKI) is common in patients with COVID-19, however, its mechanism is still controversial, particularly in ICU settings. Urinary proteinuria profile could be a non-invasive tool of interest to scrutinize the pathophysiological process underlying AKI in COVID-19 patients. MATERIAL AND METHODS: We conducted a retrospective study between March 2020 and April 2020. All patients with laboratory-confirmed COVID-19 and without end-stage kidney disease requiring renal replacement therapy before ICU admission were included. Our objectives were to assess the incidence and risk factors for AKI and to describe its clinical and biological characteristics, particularly its urinary protein profile. RESULTS: Seventy patients were included; 87% needed mechanical ventilation and 61% needed vasopressor during their ICU stay; 64.3% of patients developed AKI and half of them needed dialysis. Total and tubular proteinuria on day 1 were higher in patients with AKI, whereas glomerular proteinuria was similar in both groups. The main risk factor for AKI was shock at admission (OR = 5.47 (1.74-17.2), p < 0.01). Mortality on day 28 was higher in AKI (23/45, 51.1%) than in no-AKI patients (1/25, 4%), p < 0.001. Risk factors for 28-days mortality were AKI with need for renal replacement therapy, non-renal SOFA score and history of congestive heart failure. CONCLUSIONS: AKI is common in COVID-19 patients hospitalized in ICU; it seems to be related to tubular lesions rather than glomerular injury and is related to shock at ICU admission.

Epidemiology, risk factors and prognosis of ventilator-associated pneumonia during severe COVID-19: Multicenter observational study across 149 European Intensive Care Units.

BACKGROUND: COVID-19 patients requiring mechanical ventilation are particularly at risk of developing ventilator-associated pneumonia (VAP). Risk factors and the prognostic impact of developing VAP during critical COVID-19 have not been fully documented. METHODS: Patients invasively ventilated for at least 48 h from the prospective multicentre COVID-ICU database were included in the analyses. Cause-specific Cox regression models were used to determine factors associated with the occurrence of VAP. Cox-regression multivariable models were used to determine VAP prognosis. Risk factors and the prognostic impact of early vs. late VAP, and Pseudomonas-related vs. non-Pseudomonas-related VAP were also determined. MAIN FINDINGS: 3388 patients were analysed (63 [55-70] years, 75.8% males). VAP occurred in 1523/3388 (45.5%) patients after 7 [5-9] days of ventilation. Identified bacteria were mainly Enterobacteriaceae followed by Staphylococcus aureus and Pseudomonas aeruginosa. VAP risk factors were male gender (Hazard Ratio (HR) 1.26, 95% Confidence Interval [1.09-1.46]), concomitant bacterial pneumonia at ICU admission (HR 1.36 [1.10-1.67]), PaO2/FiO2 ratio at intubation (HR 0.99 [0.98-0.99] per 10 mmHg increase), neuromuscular-blocking agents (HR 0.89 [0.76-0.998]), and corticosteroids (HR 1.27 [1.09-1.47]). VAP was associated with 90-mortality (HR 1.34 [1.16-1.55]), predominantly due to late VAP (HR 1.51 [1.26-1.81]). The impact of Pseudomonas-related and non-Pseudomonas-related VAP on mortality was similar. CONCLUSION: VAP affected almost half of mechanically ventilated COVID-19 patients. Several risk factors have been identified, among which modifiable risk factors deserve further investigation. VAP had a specific negative impact on 90-day mortality, particularly when it occurred between the end of the first week and the third week of ventilation.

Potential of Multiplex Polymerase Chain Reaction Performed on Protected Telescope Catheter Samples for Early Adaptation of Antimicrobial Therapy in ARDS Patients.

BACKGROUND: Diagnosis of co/superinfection in patients with Acute Respiratory Distress Syndrome (ARDS) is challenging. The FilmArray Pneumonia plus Panel (bioMérieux, France), a new rapid multiplex Polymerase Chain Reaction (mPCR), has never been assessed on a blinded protected telescope catheter (PTC) samples, a very common diagnostic tool in patients under mechanical ventilation. We evaluated the performance of mPCR on PTC samples compared with conventional culture and its impact on antibiotic stewardship. METHODS: Observational study in two intensive care units, conducted between March and July 2020, during the first wave of the COVID-19 pandemic in France. RESULTS: We performed 125 mPCR on blinded PTC samples of 95 ARDS patients, including 73 (77%) SARS-CoV-2 cases and 28 (29%) requiring extracorporeal membrane oxygenation. Respiratory samples were drawn from mechanically ventilated patients either just after intubation (n = 48; 38%) or later for suspected ventilator-associated pneumonia (VAP) (n = 77; 62%). The sensitivity, specificity, positive, and negative predictive values of mPCR were 93% (95% CI 84-100), 99% (95% CI 99-100), 68% (95% CI 54-83), and 100% (95% CI 100-100), respectively. The overall coefficient of agreement between mPCR and standard culture was 0.80 (95% CI 0.68-0.89). Intensivists changed empirical antimicrobial therapy in only 14% (18/125) of cases. No new antibiotic was initiated in more than half of the CAP/HAP pneumonia-suspected cases (n = 29; 60%) and in more than one-third of those suspected to have VAP without affecting or delaying their antimicrobial therapy. CONCLUSIONS: Rapid mPCR was feasible on blinded PTC with good sensitivity and specificity. New antibiotics were not initiated in more than half of patients and more than one-third of VAP-suspected cases. Further studies are needed to assess mPCR potential in improving antibiotic stewardship.

Driving pressure-guided ventilation decreases the mechanical power compared to predicted body weight-guided ventilation in the Acute Respiratory Distress Syndrome.

BACKGROUND: Whether targeting the driving pressure (∆P) when adjusting the tidal volume in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS) may decrease the risk of ventilator-induced lung injury remains a matter of research. In this study, we assessed the effect of a ∆P-guided ventilation on the mechanical power. METHODS: We prospectively included adult patients with moderate-to-severe ARDS. Positive end expiratory pressure was set by the attending physician and kept constant during the study. Tidal volume was first adjusted to target 6 ml/kg of predicted body weight (PBW-guided ventilation) and subsequently modified within a range from 4 to 10 ml/kg PBW to target a ∆P between 12 and 14 cm H2O. The respiratory rate was then re-adjusted within a range from 12 to 40 breaths/min until EtCO2 returned to its baseline value (∆P-guided ventilation). Mechanical power was computed at each step. RESULTS: Fifty-one patients were included between December 2019 and May 2021. ∆P-guided ventilation was feasible in all but one patient. The ∆P during PBW-guided ventilation was already within the target range of ∆P-guided ventilation in five (10%) patients, above in nine (18%) and below in 36 (72%). The change from PBW- to ∆P-guided ventilation was thus accompanied by an overall increase in tidal volume from 6.1 mL/kg PBW [5.9-6.2] to 7.7 ml/kg PBW [6.2-8.7], while respiratory rate was decreased from 29 breaths/min [26-32] to 21 breaths/min [16-28] (p < 0.001 for all comparisons). ∆P-guided ventilation was accompanied by a significant decrease in mechanical power from 31.5 J/min [28-35.7] to 28.8 J/min [24.6-32.6] (p < 0.001), representing a relative decrease of 7% [0-16]. With ∆P-guided ventilation, the PaO2/FiO2 ratio increased and the ventilatory ratio decreased. CONCLUSION: As compared to a conventional PBW-guided ventilation, a ∆P-guided ventilation strategy targeting a ∆P between 12 and 14 cm H2O required to change the tidal volume in 90% of the patients. Such ∆P-guided ventilation significantly reduced the mechanical power. Whether this physiological observation could be associated with clinical benefit should be assessed in clinical trials.

Comparison of standard prophylactic, intermediate prophylactic and therapeutic anticoagulation in patients with severe COVID-19: protocol for the ANTICOVID multicentre, parallel-group, open-label, randomised controlled trial.

INTRODUCTION: COVID-19 induces venous, arterial and microvascular thrombosis, involving several pathophysiological processes. In patients with severe COVID-19 without macrovascular thrombosis, escalating into high-dose prophylactic anticoagulation (HD-PA) or therapeutic anticoagulation (TA) could be beneficial in limiting the extension of microvascular thrombosis and forestalling the evolution of lung and multiorgan microcirculatory dysfunction. In the absence of data from randomised trials, clinical practice varies widely. METHODS AND ANALYSIS: This is a French multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three anticoagulation strategies in patients with COVID-19. Patients with oxygen-treated COVID-19 showing no pulmonary artery thrombosis on computed tomography with pulmonary angiogram will be randomised to receive either low-dose PA, HD-PA or TA for 14 days. Patients attaining the extremes of weight and those with severe renal failure will not be included. We will recruit 353 patients. Patients will be randomised on a 1:1:1 basis, and stratified by centre, use of invasive mechanical ventilation, D-dimer levels and body mass index. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality, followed by the time to clinical improvement defined as the time from randomisation to an improvement of at least two points on the ordinal clinical scale. Secondary outcomes include thrombotic and major bleeding events at day 28, individual components of the primary endpoint, number of oxygen-free, ventilator-free and vasopressor-free days at day 28, D-dimer and sepsis-induced coagulopathy score at day 7, intensive care unit and hospital stay at day 28 and day 90, and all-cause death and quality of life at day 90. ETHICS AND DISSEMINATION: The study has been approved by an ethical committee (Ethics Committee, Ile de France VII, Paris, France; reference 2020-A03531-38). Patients will be included after obtaining their signed informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04808882.

Characteristics and prognosis of bloodstream infection in patients with COVID-19 admitted in the ICU: an ancillary study of the COVID-ICU study.

BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. PATIENTS AND METHODS: We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. RESULTS: Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05-1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. CONCLUSION: COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate.

Alveolar compartmentalization of inflammatory and immune cell biomarkers in pneumonia-related ARDS.

BACKGROUND: Biomarkers of disease severity might help individualizing the management of patients with the acute respiratory distress syndrome (ARDS). Whether the alveolar compartmentalization of biomarkers has a clinical significance in patients with pneumonia-related ARDS is unknown. This study aimed at assessing the interrelation of ARDS/sepsis biomarkers in the alveolar and blood compartments and explored their association with clinical outcomes. METHODS: Immunocompetent patients with pneumonia-related ARDS admitted between 2014 and 2018 were included in a prospective monocentric study. Bronchoalveolar lavage (BAL) fluid and blood samples were obtained within 48 h of admission. Twenty-two biomarkers were quantified in BAL fluid and serum. HLA-DR+ monocytes and CD8+ PD-1+ lymphocytes were quantified using flow cytometry. The primary clinical endpoint of the study was hospital mortality. Patients undergoing a bronchoscopy as part of routine care were included as controls. RESULTS: Seventy ARDS patients were included. Hospital mortality was 21.4%. The BAL fluid-to-serum ratio of IL-8 was 20 times higher in ARDS patients than in controls (p < 0.0001). ARDS patients with shock had lower BAL fluid-to-serum ratio of IL-1Ra (p = 0.026), IL-6 (p = 0.002), IP-10/CXCL10 (p = 0.024) and IL-10 (p = 0.023) than others. The BAL fluid-to-serum ratio of IL-1Ra was more elevated in hospital survivors than decedents (p = 0.006), even after adjusting for SOFA and driving pressure (p = 0.036). There was no significant association between alveolar or alveolar/blood monocytic HLA-DR or CD8+ lymphocytes PD-1 expression and hospital mortality. CONCLUSIONS: IL-8 was the most compartmentalized cytokine and lower BAL fluid-to-serum concentration ratios of IL-1Ra were associated with hospital mortality in patients with pneumonia-associated ARDS.

Continuous positive airway pressure for respiratory support during COVID-19 pandemic: a frugal approach from bench to bedside.

BACKGROUND: We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter ("Filter Frugal CPAP", FF-CPAP) in and out the ICU. METHODS: (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak. RESULTS: Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient's work of breathing (6-34%) needed to sustain the tidal volume, depending on the filter's resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO2. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p < 0.001 by log-rank test). CONCLUSION: Adding a filter to the Boussignac valve does not affect the delivered pressure but may variably increase the resistive load depending on the filter used. Clinical assessment suggests that FF-CPAP is a frugal solution to provide a ventilatory support and improve oxygenation to numerous patients suffering from AHRF in the context of a massive outbreak.

Advanced echocardiographic phenotyping of critically ill patients with coronavirus-19 sepsis: a prospective cohort study.

BACKGROUND: Sepsis is characterized by various hemodynamic alterations which could happen concomitantly in the heart, pulmonary and systemic circulations. A comprehensive demonstration of their interactions in the clinical setting of COVID-19 sepsis is lacking. This study aimed at evaluating the feasibility, clinical implications, and physiological coherence of the various indices of hemodynamic function and acute myocardial injury (AMI) in COVID-19 sepsis. METHODS: Hemodynamic and echocardiographic data of septic critically ill COVID-19 patients were prospectively recorded. A dozen hemodynamic indices exploring contractility and loading conditions were assessed. Several cardiac biomarkers were measured, and AMI was considered if serum concentration of high-sensitive troponin T (hs-TNT) was above the 99th percentile, upper reference. RESULTS: Sixty-seven patients were assessed (55 males), with a median age of 61 [50-70] years. Overall, the feasibility of echocardiographic parameters was very good, ranging from 93 to 100%. Hierarchical clustering method identified four coherent clusters involving cardiac preload, left ventricle (LV) contractility, LV afterload, and right ventricle (RV) function. LV contractility indices were not associated with preload indices, but some of them were positively correlated with RV function parameters and negatively correlated with a single LV afterload parameter. In most cases (n = 36, 54%), echocardiography results prompted therapeutic changes. Mortality was not influenced by the echocardiographic variables in multivariable analysis. Cardiac biomarkers' concentrations were most often increased with high incidence of AMI reaching 72%. hs-TNT was associated with mortality and inversely correlated with most of LV and RV contractility indices. CONCLUSIONS: In this comprehensive hemodynamic evaluation in critically ill COVID-19 septic patients, we identified four homogeneous and coherent clusters with a good feasibility. AMI was common and associated with alteration of LV and RV functions. Echocardiographic assessment had a clinical impact on patient management in most cases.

Rescue therapy with inhaled nitric oxide and almitrine in COVID-19 patients with severe acute respiratory distress syndrome.

BACKGROUND: In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for VA/Q mismatch, as hypoxic vasoconstriction alteration. This study aimed to evaluate the capacity of inhaled nitric oxide (iNO)-almitrine combination to restore oxygenation in severe COVID-19 ARDS (C-ARDS) patients. METHODS: We conducted a monocentric preliminary pilot study in intubated patients with severe C-ARDS. Respiratory mechanics was assessed after a prone session. Then, patients received iNO (10 ppm) alone and in association with almitrine (10 µg/kg/min) during 30 min in each step. Echocardiographic and blood gases measurements were performed at baseline, during iNO alone, and iNO-almitrine combination. The primary endpoint was the variation of oxygenation (PaO2/FiO2 ratio). RESULTS: Ten severe C-ARDS patients were assessed (7 males and 3 females), with a median age of 60 [52-72] years. Combination of iNO and almitrine outperformed iNO alone for oxygenation improvement. The median of PaO2/FiO2 ratio varied from 102 [89-134] mmHg at baseline, to 124 [108-146] mmHg after iNO (p = 0.13) and 180 [132-206] mmHg after iNO and almitrine (p < 0.01). We found no correlation between the increase in oxygenation caused by iNO-almitrine combination and that caused by proning. CONCLUSION: In this pilot study of severe C-ARDS patients, iNO-almitrine combination was associated with rapid and significant improvement of oxygenation. These findings highlight the role of pulmonary vascular function in COVID-19 pathophysiology.

Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease.

BACKGROUND: Data on incidence of ventilator-associated pneumonia (VAP) and invasive pulmonary aspergillosis in patients with severe SARS-CoV-2 infection are limited. METHODS: We conducted a monocenter retrospective study comparing the incidence of VAP and invasive aspergillosis between patients with COVID-19-related acute respiratory distress syndrome (C-ARDS) and those with non-SARS-CoV-2 viral ARDS (NC-ARDS). RESULTS: We assessed 90 C-ARDS and 82 NC-ARDS patients, who were mechanically ventilated for more than 48 h. At ICU admission, there were significantly fewer bacterial coinfections documented in C-ARDS than in NC-ARDS: 14 (16%) vs 38 (48%), p < 0.01. Conversely, significantly more patients developed at least one VAP episode in C-ARDS as compared with NC-ARDS: 58 (64%) vs. 36 (44%), p = 0.007. The probability of VAP was significantly higher in C-ARDS after adjusting on death and ventilator weaning [sub-hazard ratio = 1.72 (1.14-2.52), p < 0.01]. The incidence of multi-drug-resistant bacteria (MDR)-related VAP was significantly higher in C-ARDS than in NC-ARDS: 21 (23%) vs. 9 (11%), p = 0.03. Carbapenem was more used in C-ARDS than in NC-ARDS: 48 (53%), vs 21 (26%), p < 0.01. According to AspICU algorithm, there were fewer cases of putative aspergillosis in C-ARDS than in NC-ARDS [2 (2%) vs. 12 (15%), p = 0.003], but there was no difference in Aspergillus colonization. CONCLUSIONS: In our experience, we evidenced a higher incidence of VAP and MDR-VAP in C-ARDS than in NC-ARDS and a lower risk for invasive aspergillosis in the former group.

Electrical impedance tomography to titrate positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome.

RATIONALE: Patients with coronavirus disease-19-related acute respiratory distress syndrome (C-ARDS) could have a specific physiological phenotype as compared with those affected by ARDS from other causes (NC-ARDS). OBJECTIVES: To describe the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics in C-ARDS patients in supine and prone position, and as compared to NC-ARDS. The primary endpoint was the best PEEP defined as the smallest sum of hyperdistension and collapse. METHODS: Seventeen patients with moderate-to-severe C-ARDS were monitored by electrical impedance tomography (EIT) and evaluated during PEEP titration in supine (n = 17) and prone (n = 14) position and compared with 13 NC-ARDS patients investigated by EIT in our department before the COVID-19 pandemic. RESULTS: As compared with NC-ARDS, C-ARDS exhibited a higher median best PEEP (defined using EIT as the smallest sum of hyperdistension and collapse, 12 [9, 12] vs. 9 [6, 9] cmH2O, p < 0.01), more collapse at low PEEP, and less hyperdistension at high PEEP. The median value of the best PEEP was similar in C-ARDS in supine and prone position: 12 [9, 12] vs. 12 [10, 15] cmH2O, p = 0.59. The response to PEEP was also similar in C-ARDS patients with higher vs. lower respiratory system compliance. CONCLUSION: An intermediate PEEP level seems appropriate in half of our C-ARDS patients. There is no solid evidence that compliance at low PEEP could predict the response to PEEP.

Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 Acute Respiratory Distress Syndrome.

Rationale: Uncontrolled inflammatory innate response and impaired adaptive immune response are associated with clinical severity in patients with coronavirus disease (COVID-19).Objectives: To compare the immunopathology of COVID-19 acute respiratory distress syndrome (ARDS) with that of non-COVID-19 ARDS, and to identify biomarkers associated with mortality in patients with COVID-19 ARDS.Methods: Prospective observational monocenter study. Immunocompetent patients diagnosed with RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and ARDS admitted between March 8 and March 30, 2020, were included and compared with patients with non-COVID-19 ARDS. The primary clinical endpoint of the study was mortality at Day 28. Flow cytometry analyses and serum cytokine measurements were performed at Days 1-2 and 4-6 of ICU admission.Measurements and Main Results: As compared with patients with non-COVID-19 ARDS (n = 36), those with COVID-19 (n = 38) were not significantly different regarding age, sex, and Sequential Organ Failure Assessment and Simplified Acute Physiology Score II scores but exhibited a higher Day-28 mortality (34% vs. 11%, P = 0.030). Patients with COVID-19 showed profound and sustained T CD4+ (P = 0.002), CD8+ (P < 0.0001), and B (P < 0.0001) lymphopenia, higher HLA-DR expression on monocytes (P < 0.001) and higher serum concentrations of EGF (epithelial growth factor), GM-CSF, IL-10, CCL2/MCP-1, CCL3/MIP-1a, CXCL10/IP-10, CCL5/RANTES, and CCL20/MIP-3a. After adjusting on age and Sequential Organ Failure Assessment, serum CXCL10/IP-10 (P = 0.047) and GM-CSF (P = 0.050) were higher and nasopharyngeal RT-PCR cycle threshold values lower (P = 0.010) in patients with COVID-19 who were dead at Day 28.Conclusions: Profound global lymphopenia and a "chemokine signature" were observed in COVID-19 ARDS. Increased serum concentrations of CXCL10/IP-10 and GM-CSF, together with higher nasopharyngeal SARS-CoV-2 viral load, were associated with Day-28 mortality.

Feasibility of Prone Position Coronary Angiography in a Patient With COVID-19 Pneumonia and Refractory Hypoxemia.

A 57-year-old woman hospitalized for a COVID-19 (coronavirus disease-2019)-related refractory acute respiratory distress syndrome developed a few days later anteroseptal ST-segment elevation with acute systolic dysfunction. Coronary angiography was performed with the patient in prone (face down) position, owing to the necessity to maintain a reasonable oxygen saturation during the examination. (Level of Difficulty: Intermediate.).