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2.
PLoS One ; 16(11): e0260656, 2021.
Article in English | MEDLINE | ID: covidwho-1533423

ABSTRACT

Therapeutic drug monitoring (TDM) is essential for voriconazole to ensure optimal drug exposure, mainly in critically ill patients for whom voriconazole demonstrated a large variability. The study aimed at describing factors associated with trough voriconazole concentrations in critically ill patients and evaluating the impact of voriconazole concentrations on adverse effects. A 2-year retrospective multicenter cohort study (NCT04502771) was conducted in six intensive care units. Adult patients who had at least one voriconazole TDM were included. Univariable and multivariable linear regression analyses were performed to identify predictors of voriconazole concentrations, and univariable logistic regression analysis, to study the relationship between voriconazole concentrations and adverse effects. During the 2-year study period, 70 patients were included. Optimal trough voriconazole concentrations were reported in 37 patients (52.8%), subtherapeutic in 20 (28.6%), and supratherapeutic in 13 (18.6%). Adverse effects were reported in six (8.6%) patients. SOFA score was identified as a factor associated with an increase in voriconazole concentration (p = 0.025), mainly in the group of patients who had SOFA score ≥ 10. Moreover, an increase in voriconazole concentration was shown to be a risk factor for occurrence of adverse effects (p = 0.011). In that respect, critically ill patients who received voriconazole treatment must benefit from a TDM, particularly if they have a SOFA score ≥ 10. Indeed, identifying patients who are overdosed will help to prevent voriconazole related adverse effects. This result is of utmost importance given the recognized COVID-19-associated pulmonary aspergillosis in ICU patients for whom voriconazole is among the recommended first-line treatment.

3.
Lancet Respir Med ; 2021 Nov 11.
Article in English | MEDLINE | ID: covidwho-1510505

ABSTRACT

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury. METHODS: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580. FINDINGS: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089). INTERPRETATION: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. FUNDING: Programme Hospitalier de Recherche Clinique.

4.
Eur J Cardiovasc Nurs ; 20(8): 792-796, 2021 11 28.
Article in English | MEDLINE | ID: covidwho-1483429

ABSTRACT

AIMS: Prone positioning is increasingly used for treating coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS). In these high-risk patients for cardiovascular events who may spend more than 16 h a day in the prone position, an adequate monitoring of electrocardiogram (ECG) is mandatory. However, effects of prone positioning on the ECG are unknown as is the validity of the ECG recorded with electrodes placed dorsally. We aimed to compare ECG data obtained in the prone position from five electrodes positioned conventionally and dorsally, and to assess the effects of the change of position (from supine to prone) on the ECGs in patients with COVID-19 ARDS. METHODS AND RESULTS: In patients with COVID-19 ARDS for whom the prone position was indicated, seven-lead ECG (frontal plane leads and V6) performed in the supine and the prone position with electrodes positioned conventionally and dorsally were compared. A total of 22 patients [20 (91%) males] were included. Among them, 10 (45%) patients had structural or ischaemic heart disease. After prone positioning, PR duration significantly increased and QRS duration significantly decreased whereas QT interval did not significantly change. In the prone position, there were excellent correlations between QRS axis, PR, RR, QRS, and QT intervals durations measured with electrodes placed on the torso and dorsally (with no change in the position of V6). CONCLUSION: Prone positioning induced significant change in the ECG. In the prone position, ECG can be reliably monitored with four electrodes translated from conventional position to the back and with a precordial electrode left in V6 position.

5.
J Intensive Care ; 9(1): 64, 2021 Oct 18.
Article in English | MEDLINE | ID: covidwho-1477471

ABSTRACT

Dexamethasone improves survival of patients with COVID-19 acute respiratory distress syndrome, but might shorten the delay between the start of invasive mechanical ventilation and the occurrence of ventilator-associated pneumonia, suggesting possible worsening of COVID-19-induced immune dysfunction with this treatment. In a prospective observational study, we found that mechanically ventilated patients with COVID-19 treated with dexamethasone presented earlier ventilator-associated pneumonia, had significantly lower monocyte Human Leukocyte Antigen-DR expression and number of circulating CD4 + cells after ICU admission, than those not treated with corticoids.

6.
Trials ; 22(1): 692, 2021 Oct 11.
Article in English | MEDLINE | ID: covidwho-1463262

ABSTRACT

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.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Adult , Extracorporeal Circulation , Humans , Prospective Studies , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , SARS-CoV-2
7.
Crit Care Med ; 2021 Sep 24.
Article in English | MEDLINE | ID: covidwho-1440666

ABSTRACT

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.

8.
Arch Med Res ; 52(8): 850-857, 2021 11.
Article in English | MEDLINE | ID: covidwho-1427555

ABSTRACT

BACKGROUND: As COVID-19 pandemic and vaccination effects progress, research now focuses on adaptive immunological response to SARS-CoV-2. Few studies specifically investigated intensive care unit (ICU) patients, and little is known about kinetics of humoral response in such critically ill patients. In this context, the main objective of the present work was to perform a longitudinal analysis of the humoral response in critically ill COVID-19 patients with prolonged ICU stays in regard with initial inflammatory response, disease severity and mortality. METHODS: Over a 3 week period, circulating immunoglobulins (Ig) against SARS-CoV-2 along with several immunological and clinical parameters were measured in 64 ICU COVID-19 patients. RESULTS: Critically ill COVID-19 patients mounted a dynamic and sustained antibody response of both IgM and IgG as soon as the first day of ICU hospitalization. This serological response was not associated with any of the classical immunological parameters measured at ICU admission or with initial severity clinical scores. IgM and IgG levels and seroconversion trajectories were not associated with unfavourable outcome. CONCLUSION: Despite rapid seroconversion and elevated humoral response, COVID-19 patients are still characterized by elevated mortality. Additional studies, including cytotoxic T cell functions, are mandatory to understand the immunological mechanisms contributing to long stay of COVID-19 patients in ICU.

9.
BMJ Open ; 11(8): e048187, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1376500

ABSTRACT

INTRODUCTION: At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care. METHODS AND ANALYSIS: The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician's discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period. ETHICS AND DISSEMINATION: The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses. TRIAL REGISTRATION NUMBER: NCT03452826; Pre-results.


Subject(s)
COVID-19 , Pneumonia , Adult , Anti-Bacterial Agents/therapeutic use , Humans , Intensive Care Units , Multiplex Polymerase Chain Reaction , Pneumonia/drug therapy , Procalcitonin
10.
BMJ Open ; 11(7): e044449, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1299231

ABSTRACT

INTRODUCTION: With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission. METHODS AND ANALYSIS: This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients' outcomes. ETHICS AND DISSEMINATION: The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04422340.


Subject(s)
COVID-19 , Aged , France/epidemiology , Humans , Intensive Care Units , Middle Aged , Multicenter Studies as Topic , Risk Factors , SARS-CoV-2 , Surveys and Questionnaires
11.
J Leukoc Biol ; 2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1293207

ABSTRACT

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with immunosuppressive properties. In cancer patients, the expression of lectin-type oxidized LDL receptor 1 (LOX-1) on granulocytic MDSC identifies a subset of MDSC that retains the most potent immunosuppressive properties. The main objective of the present work was to explore the presence of LOX-1+ MDSC in bacterial and viral sepsis. To this end, whole blood LOX-1+ cells were phenotypically, morphologically, and functionally characterized. They were monitored in 39 coronavirus disease-19 (COVID-19, viral sepsis) and 48 septic shock (bacterial sepsis) patients longitudinally sampled five times over a 3 wk period in intensive care units (ICUs). The phenotype, morphology, and immunosuppressive functions of LOX-1+ cells demonstrated that they were polymorphonuclear MDSC. In patients, we observed the significant emergence of LOX-1+ MDSC in both groups. The peak of LOX-1+ MDSC was 1 wk delayed with respect to ICU admission. In COVID-19, their elevation was more pronounced in patients with acute respiratory distress syndrome. The persistence of these cells may contribute to long lasting immunosuppression leaving the patient unable to efficiently resolve infections.

13.
Chest ; 160(3): 944-955, 2021 09.
Article in English | MEDLINE | ID: covidwho-1275208

ABSTRACT

BACKGROUND: Working in the ICU during the first COVID-19 wave was associated with high levels of mental health disorders. RESEARCH QUESTION: What are the mental health symptoms in health care providers (HCPs) facing the second wave? STUDY DESIGN AND METHODS: A cross-sectional study (October 30-December 1, 2020) was conducted in 16 ICUs during the second wave in France. HCPs completed the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised (for post-traumatic stress disorder), and the Maslach Burnout Inventory. RESULTS: Of 1,203 HCPs, 845 responded (70%) (66% nursing staff, 32% medical staff, 2% other professionals); 487 (57.6%) had treated more than 10 new patients with COVID-19 in the previous week. Insomnia affected 320 (37.9%), and 7.7% were taking a psychotropic drug daily. Symptoms of anxiety, depression, post-traumatic stress disorder, and burnout were reported in 60.0% (95% CI, 56.6%-63.3%), 36.1% (95% CI, 32.9%-39.5%), 28.4% (95% CI, 25.4%-31.6%), and 45.1% (95% CI, 41.7%-48.5%) of respondents, respectively. Independent predictors of such symptoms included respondent characteristics (sex, profession, experience, personality traits), work organization (ability to rest and to care for family), and self-perceptions (fear of becoming infected or of infecting family and friends, feeling pressure related to the surge, intention to leave the ICU, lassitude, working conditions, feeling they had a high-risk profession, and "missing the clapping"). The number of patients with COVID-19 treated in the first wave or over the last week was not associated with symptoms of mental health disorders. INTERPRETATION: The prevalence of symptoms of mental health disorders is high in ICU HCPs managing the second COVID-19 surge. The highest tiers of hospital management urgently need to provide psychological support, peer-support groups, and a communication structure that ensure the well-being of HCPs.


Subject(s)
Anxiety/epidemiology , COVID-19/complications , Critical Care , Depression/epidemiology , Health Personnel/psychology , Mental Health , Physicians/psychology , Adult , Anxiety/etiology , Burnout, Professional/psychology , COVID-19/epidemiology , Cross-Sectional Studies , Depression/etiology , Female , France/epidemiology , Humans , Male , Pandemics , Prevalence
14.
Cytometry B Clin Cytom ; 2021 Jun 12.
Article in English | MEDLINE | ID: covidwho-1265376

ABSTRACT

BACKGROUND: Diminished expression of human leukocyte antigen DR on circulating monocytes (mHLA-DR), measured by standardized flow cytometry procedure, is a reliable indicator of immunosuppression in severely injured intensive care unit patients. As such, it is used as stratification criteria in clinical trials evaluating novel immunostimulating therapies. Preanalytical constraints relative to the short delay between blood sampling and flow cytometry staining have nevertheless limited its use in multicentric studies. The objective of the present work was to compare mHLA-DR expression between whole blood samples simultaneously drawn in EDTA or Cyto-Chex BCT tubes. METHODS: In two university hospitals, mHLA-DR was assessed in fresh whole blood from septic patients (n = 12) and healthy donors (n = 6) simultaneously sampled on EDTA and Cyto-Chex BCT tubes. Staining was performed immediately after sampling and after blood storage at room temperature. RESULTS: We confirmed that samples collected in Cyto-Chex tube had substantially enhanced stability for mHLA-DR results (48-72 h) over those collected in EDTA. On baseline values, despite good correlation between tubes (r = 0.98, p < 0.001), mHLA-DR expression was systematically lower with Cyto-Chex BCT. CONCLUSION: The present reports confirms the potential of Cyto-Chex BCT tubes to stabilize mHLA-DR expression before staining and extends the work of Quadrini et al. [Cytometry B 2021;100:103-114]. In centers without rapid access to flow cytometry facilities, it enables to tolerate delays in mHLA-DR staining. However, a 30% gap exists between results obtained with EDTA and Cyto-Chex BCT tubes. As current thresholds for clinical decisions were obtained with EDTA samples, further studies are needed to confirm clinical thresholds with Cyto-Chex BCT tubes.

15.
BMJ Open ; 11(5): e045041, 2021 05 11.
Article in English | MEDLINE | ID: covidwho-1259009

ABSTRACT

INTRODUCTION: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. METHODS AND ANALYSIS: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. ETHICS AND DISSEMINATION: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03573739.


Subject(s)
COVID-19 , Diet, Protein-Restricted , Adult , Critical Illness , Humans , Respiration, Artificial , SARS-CoV-2
16.
Heart Lung ; 50(5): 700-705, 2021.
Article in English | MEDLINE | ID: covidwho-1252961

ABSTRACT

BACKGROUND: Lung ultrasound can accurately detect pandemic coronavirus disease (COVID-19) pulmonary lesions. A lung ultrasound score (LUS) was developed to improve reproducibility of the technique. OBJECTIVES: To evaluate the clinical value of LUS monitoring to guide COVID-19-associated acute respiratory distress syndrome (ARDS) management. METHODS: We conducted a single center, prospective observational study, including all patients admitted with COVID-19-associated ARDS between March and April 2020. A systematic daily LUS evaluation was performed. RESULTS: Thirty-three consecutive patients were included. LUS was significantly and negatively correlated to PaO2/FIO2. LUS increased significantly over time in non-survivors compared to survivors. LUS increased in 83% of ventilatory associated pneumonia (VAP) episodes, when compared to the previous LUS evaluation. LUS was not significantly higher in patients presenting post-extubation respiratory failure. CONCLUSIONS: In conclusion, our study demonstrates that LUS variations are correlated to disease severity and progression, and LUS monitoring could contribute to the early diagnosis of VAPs.


Subject(s)
COVID-19 , Pneumonia, Ventilator-Associated , Respiratory Distress Syndrome , Disease Progression , Humans , Lung/diagnostic imaging , Pneumonia, Ventilator-Associated/diagnosis , Reproducibility of Results , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Ultrasonography
17.
Ann Transl Med ; 9(7): 524, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1229549

ABSTRACT

Background: There are limited data on the effect of hydroxychloroquine on medium term outcomes in patients with coronavirus disease 2019 (COVID-19) requiring intensive care. We aimed to evaluate the effects of hydroxychloroquine on day 90 mortality in this specific population. Methods: This retrospective, multicenter, propensity matched cohort analysis, used data of adult patients with laboratory confirmed COVID-19 admitted to 3 university affiliated intensive care units between March 7, 2020, to April 7, 2020 in Lyon, France. Patients received either hydroxychloroquine (loading dose of 400 mg twice daily at day 1 followed by 200 mg twice daily from day 2 to day 10) or standard of care without hydroxychloroquine. We compared all-cause mortality at day-90 after ICU admission between propensity score matched groups receiving hydroxychloroquine or standard of care. Results: A total of 157 patients were included with a day-28 and day-90 mortality rate of 23.6% and 32.5%, respectively. The median (interquartile) age was 67 years (56-76 years), 105 (66.9%) were men, 65 (41.4%) fulfilled criteria for acute respiratory distress syndrome, and 64 (41%) received hydroxychloroquine (HCQ) for 10 days (4-10 days). In the propensity score matched cohort (59 patients in each group), day-90 mortality was 35.6% for patients who received HCQ and 23.7% for patients who did not (P=0.23). Kaplan Meier survival analysis showed no statistically significant association between HCQ therapy and mortality (P=0.20 by log-rank test). Conclusions: In this study, off-label use of HCQ in critically ill patients with COVID-19 was not associated with any significant change in medium-term prognosis, confirming results of studies in less severe patients.

18.
Crit Care ; 25(1): 140, 2021 04 12.
Article in English | MEDLINE | ID: covidwho-1181117

ABSTRACT

BACKGROUND: Since the onset of the pandemic, only few studies focused on longitudinal immune monitoring in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) whereas their hospital stay may last for several weeks. Consequently, the question of whether immune parameters may drive or associate with delayed unfavorable outcome in these critically ill patients remains unsolved. METHODS: We present a dynamic description of immuno-inflammatory derangements in 64 critically ill COVID-19 patients including plasma IFNα2 levels and IFN-stimulated genes (ISG) score measurements. RESULTS: ARDS patients presented with persistently decreased lymphocyte count and mHLA-DR expression and increased cytokine levels. Type-I IFN response was initially induced with elevation of IFNα2 levels and ISG score followed by a rapid decrease over time. Survivors and non-survivors presented with apparent common immune responses over the first 3 weeks after ICU admission mixing gradual return to normal values of cellular markers and progressive decrease of cytokines levels including IFNα2. Only plasma TNF-α presented with a slow increase over time and higher values in non-survivors compared with survivors. This paralleled with an extremely high occurrence of secondary infections in COVID-19 patients with ARDS. CONCLUSIONS: Occurrence of ARDS in response to SARS-CoV2 infection appears to be strongly associated with the intensity of immune alterations upon ICU admission of COVID-19 patients. In these critically ill patients, immune profile presents with similarities with the delayed step of immunosuppression described in bacterial sepsis.


Subject(s)
COVID-19/blood , Critical Illness , Intensive Care Units/trends , Interferon-alpha/blood , Respiratory Distress Syndrome/blood , Adult , Aged , Biomarkers/blood , COVID-19/epidemiology , COVID-19/immunology , Critical Illness/epidemiology , Female , Hospitalization/trends , Humans , Immunity/immunology , Longitudinal Studies , Male , Middle Aged , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/immunology
20.
Cytometry A ; 99(5): 466-471, 2021 05.
Article in English | MEDLINE | ID: covidwho-1064342

ABSTRACT

During the second surge of COVID-19 in France (fall 2020), we assessed the expression of monocyte CD169 (i.e., Siglec-1, one of the numerous IFN-stimulated genes) upon admission to intensive care units of 45 patients with RT-PCR-confirmed SARS-CoV2 pulmonary infection. Overall, CD169 expression was strongly induced on circulating monocytes of COVID-19 patients compared with healthy donors and patients with bacterial sepsis. Beyond its contribution at the emergency department, CD169 testing may be also helpful for patients' triage at the ICU to rapidly reinforce suspicion of COVID-19 etiology in patients with acute respiratory failure awaiting for PCR results for definitive diagnosis.


Subject(s)
COVID-19/blood , Intensive Care Units , Monocytes/metabolism , Patient Admission , SARS-CoV-2/pathogenicity , Sialic Acid Binding Ig-like Lectin 1/blood , Adult , Aged , Biomarkers/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Female , Flow Cytometry , Host-Pathogen Interactions , Humans , Male , Middle Aged , Monocytes/immunology , Monocytes/virology , Predictive Value of Tests , Preliminary Data , Prognosis , Prospective Studies , SARS-CoV-2/immunology , Up-Regulation
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