15 research outputs found

    Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

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    RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BA.1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir

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    International audienceObjectives: Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients who received Sotrovimab or Nirmatrelvir to prevent severe COVID-19.Methods: In the multicentric prospective ANRS 0003S CoCoPrev cohort study, patients at high-risk for progression with mild-to-moderate BA.1 or BA.2 COVID-19 who received Sotrovimab or Nirmatrelvir were included. Proportion of patients with progression to severe COVID-19, time between the start of treatment to negative PCR, SARS-CoV-2 viral decay, and characterization of resistance variants were determined. A multivariable Cox proportional hazard model was used for time to negative PCR and a mixed effect model for the dynamics of viral decay.Results: Among the 255 included patients, of whom 199/255 (80%) received ≥3 vaccine doses, 195/255 (76%) received Sotrovimab and 60/255 (24%) received Nirmatrelvir. At day 28, new COVID-19-related hospitalization occurred in 4/193 (2%, 95%CI 1-5%) Sotrovimab-treated patients, and 0/55 Nirmatrelvir-treated patient (p=0.24). One out of 55 Nirmatrelvir-treated patients died (2%, 95%CI 0-10%). The median time to negative PCR was 11.5 days (95%CI 10.5-13) in Sotrovimab-treated patients vs. 4 days (95% CI 4-9) in Nirmatrelvir-treated patients (p<0.001). Viral decay was faster in patients who received Nirmatrelvir (p<0.001). In multivariable analysis Nirmatrelvir and nasopharyngeal PCR cycle threshold value were independently associated with a faster conversion to negative PCR (HR 2.35, 95%CI 1.56-3.56, p<0.0001, and HR 1.05, 95%CI 1.01-1.08, p=0.01, respectively).Conclusions: Early administration of Nirmatrelvir in high-risk patients, compared to Sotrovimab, was associated with a faster viral clearance. This may participate to decrease transmission and prevent viral resistance

    Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BA.1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir

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    International audienceObjectives: Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients who received Sotrovimab or Nirmatrelvir to prevent severe COVID-19.Methods: In the multicentric prospective ANRS 0003S CoCoPrev cohort study, patients at high-risk for progression with mild-to-moderate BA.1 or BA.2 COVID-19 who received Sotrovimab or Nirmatrelvir were included. Proportion of patients with progression to severe COVID-19, time between the start of treatment to negative PCR, SARS-CoV-2 viral decay, and characterization of resistance variants were determined. A multivariable Cox proportional hazard model was used for time to negative PCR and a mixed effect model for the dynamics of viral decay.Results: Among the 255 included patients, of whom 199/255 (80%) received ≥3 vaccine doses, 195/255 (76%) received Sotrovimab and 60/255 (24%) received Nirmatrelvir. At day 28, new COVID-19-related hospitalization occurred in 4/193 (2%, 95%CI 1-5%) Sotrovimab-treated patients, and 0/55 Nirmatrelvir-treated patient (p=0.24). One out of 55 Nirmatrelvir-treated patients died (2%, 95%CI 0-10%). The median time to negative PCR was 11.5 days (95%CI 10.5-13) in Sotrovimab-treated patients vs. 4 days (95% CI 4-9) in Nirmatrelvir-treated patients (p<0.001). Viral decay was faster in patients who received Nirmatrelvir (p<0.001). In multivariable analysis Nirmatrelvir and nasopharyngeal PCR cycle threshold value were independently associated with a faster conversion to negative PCR (HR 2.35, 95%CI 1.56-3.56, p<0.0001, and HR 1.05, 95%CI 1.01-1.08, p=0.01, respectively).Conclusions: Early administration of Nirmatrelvir in high-risk patients, compared to Sotrovimab, was associated with a faster viral clearance. This may participate to decrease transmission and prevent viral resistance

    Protocol for fever control using external cooling in mechanically ventilated patients with septic shock: SEPSISCOOL II randomised controlled trial

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    Introduction Fever treatment is commonly applied in patients with sepsis but its impact on survival remains undetermined. Patients with respiratory and haemodynamic failure are at the highest risk for not tolerating the metabolic cost of fever. However, fever can help to control infection. Treating fever with paracetamol has been shown to be less effective than cooling. In the SEPSISCOOL pilot study, active fever control by external cooling improved organ failure recovery and early survival. The main objective of this confirmatory trial is to assess whether fever control at normothermia can improve the evolution of organ failure and mortality at day 60 of febrile patients with septic shock. This study will compare two strategies within the first 48 hours of septic shock: treatment of fever with cooling or no treatment of fever.Methods and analysis SEPSISCOOL II is a pragmatic, investigator-initiated, adaptive, multicentre, open-label, randomised controlled, superiority trial in patients admitted to the intensive care unit with febrile septic shock. After stratification based on the acute respiratory distress syndrome status, patients will be randomised between two arms: (1) cooling and (2) no cooling. The primary endpoint is mortality at day 60 after randomisation. The secondary endpoints include the evolution of organ failure, early mortality and tolerance. The target sample size is 820 patients.Ethics and dissemination The study is funded by the French health ministry and was approved by the ethics committee CPP Nord Ouest II (Amiens, France). The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT04494074

    Convalescent plasma therapy for B-cell depleted patients with protracted COVID-19 disease

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    International audienceAnti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2-antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative IgG-IgM SARS-CoV-2 serology and a positive RNAemia measured by digital PCR who were treated with four units of COVID-19 convalescent plasma. Within 48 hours following transfusion, all patients except one experienced an amelioration of their clinical symptoms. The inflammatory syndrome abated within a week. Only one patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in 9 out of 9 evaluated patients. Analysis of virus-specific T-cell responses using T-cell enzyme linked immunoSpot (ELISPOT) assay was analyzed before convalescent plasma transfusion in 3 patients. All showed a conserved SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. In COVID-19 patients unable to mount a specific humoral response to SARS-CoV-2, convalescent plasma with anti-SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms

    Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3)

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    Can Biomarkers Correctly Predict Ventilator-associated Pneumonia in Patients Treated With Targeted Temperature Management After Cardiac Arrest? An Exploratory Study of the Multicenter Randomized Antibiotic (ANTHARTIC) Study

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    IMPORTANCE:. Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES:. To evaluate biomarkers’ impact in helping VAP diagnosis after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS:. This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES:. The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS:. Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C–C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE:. Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients

    Sotrovimab therapy elicits antiviral activities against Omicron BQ.1.1 and XBB.1.5 in sera of immunocompromised patients [letter]

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    Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome Associated with COVID-19: An Emulated Target Trial Analysis

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    International audienc
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