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

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/)

MOESM1 of High-flow nasal cannula oxygen therapy versus noninvasive ventilation in immunocompromised patients with acute respiratory failure: an observational cohort study

Additional file 1. Univariate analysis of variables associated with intubation in the overall population

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

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

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

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

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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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

International audienc

Benefits and risks of noninvasive oxygenation strategy in COVID-19: a multicenter, prospective cohort study (COVID-ICU) in 137 hospitals

International audienceAbstract Rational To evaluate the respective impact of standard oxygen, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) on oxygenation failure rate and mortality in COVID-19 patients admitted to intensive care units (ICUs). Methods Multicenter, prospective cohort study (COVID-ICU) in 137 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, oxygenation failure, and survival data were collected. Oxygenation failure was defined as either intubation or death in the ICU without intubation. Variables independently associated with oxygenation failure and Day-90 mortality were assessed using multivariate logistic regression. Results From February 25 to May 4, 2020, 4754 patients were admitted in ICU. Of these, 1491 patients were not intubated on the day of ICU admission and received standard oxygen therapy (51%), HFNC (38%), or NIV (11%) ( P < 0.001). Oxygenation failure occurred in 739 (50%) patients (678 intubation and 61 death). For standard oxygen, HFNC, and NIV, oxygenation failure rate was 49%, 48%, and 60% ( P < 0.001). By multivariate analysis, HFNC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.36–0.99, P = 0.013) but not NIV (OR 1.57, 95% CI 0.78–3.21) was associated with a reduction in oxygenation failure). Overall 90-day mortality was 21%. By multivariable analysis, HFNC was not associated with a change in mortality (OR 0.90, 95% CI 0.61–1.33), while NIV was associated with increased mortality (OR 2.75, 95% CI 1.79–4.21, P < 0.001). Conclusion In patients with COVID-19, HFNC was associated with a reduction in oxygenation failure without improvement in 90-day mortality, whereas NIV was associated with a higher mortality in these patients. Randomized controlled trials are needed