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1.
EClinicalMedicine ; 46: 101362, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1959481

ABSTRACT

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42-1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19-20-0151, PHRC COVID-19-20-0029], Fondation de l'Assistance Publique - Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale" (FRM). Tocilizumab was provided by Roche.

2.
PLoS One ; 17(7): e0271358, 2022.
Article in English | MEDLINE | ID: covidwho-1938449

ABSTRACT

PURPOSE: To compare the characteristics, management, and prognosis of patients admitted to intensive care units (ICU) for coronavirus disease (COVID)-19 during the first two waves of the outbreak and to evaluate the relationship between ICU strain (ICU demand due to COVID-19 admissions) and mortality. METHODS: In a multicentre retrospective study, 1166 COVID-19 patients admitted to five ICUs in France between 20 February and 31 December 2020 were included. Data were collected at each ICU from medical records. A Cox proportional-hazards model identified factors associated with 28-day mortality. RESULTS: 640 patients (55%) were admitted during the first wave (February to June 2020) and 526 (45%) during the second wave (July to December 2020). ICU strain was lower during the second wave (-0.81 [-1.04 --0.31] vs. 1.18 [-0.34-1.29] SD when compared to mean COVID-19 admission in each center during study period, P<0.001). Patients admitted during the second wave were older, had more profound hypoxemia and lower SOFA. High flow nasal cannula was more frequently used during the second wave (68% vs. 39%, P<0.001) and intubation was less frequent (46% vs. 69%, P<0.001). Neither 28-day mortality (30% vs. 26%, P = 0.12) nor hospital mortality (37% vs. 31%, P = 0.27) differed between first and second wave. Overweight and obesity were associated with lower 28-day mortality while older age, underlying chronic kidney disease, severity at ICU admission as assessed by SOFA score and ICU strain were associated with higher 28-day mortality. ICU strain was not associated with hospital mortality. CONCLUSION: The characteristics and the management of patients varied between the first and the second wave of the pandemic. Rather than the wave, ICU strain was independently associated with 28-day mortality, but not with hospital mortality.


Subject(s)
COVID-19 , COVID-19/epidemiology , Hospital Mortality , Humans , Intensive Care Units , Pandemics , Retrospective Studies
3.
Minerva Anestesiol ; 88(7-8): 580-587, 2022.
Article in English | MEDLINE | ID: covidwho-1934884

ABSTRACT

BACKGROUND: SARS-CoV-2 pneumonia is responsible for unprecedented numbers of acute respiratory failure requiring invasive mechanical ventilation (IMV). This work aimed to assess whether adding face-mask noninvasive ventilation (NIV) to high-flow nasal oxygen (HFNO) was associated with a reduced need for endotracheal intubation. METHODS: This retrospective cohort study was conducted from July 2020 to January 2021 in two tertiary care intensive care units (ICUs) in Paris, France. Patients admitted for laboratory confirmed SARS-CoV-2 infection with acute hypoxemic respiratory failure requiring HFNO with or without NIV were included. The primary outcome was the rate of endotracheal intubation. Secondary outcomes included day-28 mortality, day-28 respiratory support and IMV free days, ICU and hospital length-of-stay. Sensitivity analyses with both propensity score matching and overlap weighting were used. RESULTS: One hundred twenty-eight patients were included, 88 (69%) received HFNO alone and 40 (31%) received additional NIV. Additional NIV was associated with a reduced rate of endotracheal intubation in multivariate analysis (53 [60%] vs. 15 [38%], HR=0.46 [95% CI: 0.23-0.95], P=0.04). Sensitivity analyses by propensity score matching (HR=0.45 [95% CI: 0.24-0.84], P=0.01) and overlap weighting (HR=0.52 [95% CI: 0.28-0.94], P=0.03) were consistent. Day-28 mortality was 25 (28%) in the HFNO group and 8 (20%) in the NIV group (HR=0.75 [95% CI: 0.15-3.82], P=0.72). NIV was associated with higher IMV free days (20 [0-28] vs. 28 [14-28], P=0.015). All sensitivity analyses were consistent regarding secondary outcomes. CONCLUSIONS: Need for endotracheal intubation was lower in critically-ill SARS-CoV-2 patients receiving face-mask noninvasive mechanical ventilation in addition to high-flow oxygen therapy.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Insufficiency , COVID-19/therapy , Cohort Studies , Critical Illness/therapy , Humans , Intensive Care Units , Intubation, Intratracheal , Oxygen , Propensity Score , Respiration, Artificial , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2
4.
Sci Rep ; 12(1): 9502, 2022 06 09.
Article in English | MEDLINE | ID: covidwho-1886229

ABSTRACT

The local immune-inflammatory response elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still poorly described, as well as the extent to which its characteristics may be associated with the outcome of critical Coronavirus disease 2019 (COVID-19). In this prospective monocenter study, all consecutive COVID-19 critically ill patients admitted from February to December 2020 and explored by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) were included. Biological assays, including digital ELISA cytokine profiling and targeted eicosanoid metabolomic analysis, were performed on paired blood and BAL fluid (BALF). Clinical outcome was assessed through the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) at the 28th day (D28) following the admission to intensive care unit. A D28-WHO-CPS value higher than 5 defined a poor outcome. Seventy-six patients were included, 45 (59%) had a poor day-28 outcome. As compared to their counterparts, patients with D28-WHO-CPS > 5 exhibited a neutrophil-predominant bronchoalveolar phenotype, with a higher BALF neutrophil/lymphocyte ratio, a blunted local type I interferon response, a decompartimentalized immune-inflammatory response illustrated by lower BALF/blood ratio of concentrations of IL-6 (1.68 [0.30-4.41] vs. 9.53 [2.56-19.1]; p = 0.001), IL-10, IL-5, IL-22 and IFN-γ, and a biological profile of vascular endothelial injury illustrated by a higher blood concentration of VEGF and higher blood and/or BALF concentrations of several vasoactive eicosanoids. In critically ill COVID-19 patients, we identified bronchoalveolar and blood immune-inflammatory biomarker signature associated with poor 28-day outcome.


Subject(s)
COVID-19 , Biomarkers , Bronchoalveolar Lavage Fluid , Critical Illness , Humans , Prospective Studies , SARS-CoV-2
5.
BMJ Open ; 12(4): e059383, 2022 04 26.
Article in English | MEDLINE | ID: covidwho-1816767

ABSTRACT

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.


Subject(s)
COVID-19 , Anticoagulants/therapeutic use , Blood Coagulation , Humans , Microcirculation , Multicenter Studies as Topic , Quality of Life , Randomized Controlled Trials as Topic
6.
Hemato ; 3(1):204-219, 2022.
Article in English | MDPI | ID: covidwho-1732001

ABSTRACT

In some patients, SARS-CoV-2 infection induces cytokine storm, hypercoagulability and endothelial cell activation leading to worsening of COVID-19, intubation and death. Prompt identification of patients at risk of intubation is an urgent need. Objectives. To derive a prognostic score for the risk of intubation or death in patients with COVID-19 admitted in intensive care unit (ICU), by assessing biomarkers of hypercoagulability, endothelial cell activation and inflammation and a large panel of clinical analytes. Design, Setting and Participants. A prospective, observational study enrolled 118 patients with COVID-19 admitted in the ICU. On the first day of ICU admission, all patients were assessed for biomarkers (protein C, protein S, antithrombin, D-Dimer, fibrin monomers, FVIIa, FV, FXII, FXII, FVIII, FvW antigen, fibrinogen, procoagulant phospholipid dependent clotting time, TFPI, thrombomodulin, P-selectin, heparinase, microparticles exposing TF, IL-6, complement C3a, C5a, thrombin generation, PT, aPTT, hemogram, platelet count) and clinical predictors. Main Outcomes and Measures. The clinical outcomes were intubation and mortality during hospitalization in ICU. Results: The intubation and mortality rates were 70% and 18%, respectively. The COMPASS-COVID-19-ICU score composed of P-Selectin, D-Dimer, free TFPI, TF activity, IL-6 and FXII, age and duration of hospitalization predicted the risk of intubation or death with high sensitivity and specificity (0.90 and 0.92, respectively). Conclusions and Relevance. COVID-19 is related to severe endothelial cell activation and hypercoagulability orchestrated in the context of inflammation. The COMPASS-COVID-19-ICU risk assessment model is accurate for the evaluation of the risk of mechanical ventilation and death in patients with critical COVID-19. The COMPASS-COVID-19-ICU score is feasible in tertiary hospitals and could be placed in the diagnostic procedure of personalized medical management and prompt therapeutic intervention.

7.
Crit Care ; 26(1): 48, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1703362

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS. METHODS: This multicentre, double-blind, randomized, placebo-controlled trial (STROMA-CoV-2) recruited adults (≥ 18 years) with SARS-CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 106 UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO2/FiO2)-ratio change between baseline (day (D) 0) and D7. RESULTS: Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO2/FiO2 changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [- 15.5 to 93.3] vs 25.3 [- 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI - 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment. CONCLUSIONS: D0-to-D7 PaO2/FiO2 changes for intravenous UC-MSCs-versus placebo-treated adults with SARS-CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context. TRIAL REGISTRATION: NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 .


Subject(s)
COVID-19 , Mesenchymal Stem Cells , Respiratory Distress Syndrome , Double-Blind Method , Humans , Respiratory Distress Syndrome/therapy , SARS-CoV-2 , Treatment Outcome
8.
Vieillard-Baron, Antoine, Flicoteaux, Rémi, Salmona, Maud, Annane, Djillali, Ayed, Soufia, Azoulay, Elie, Bellaiche, Raphael, Beloucif, Sadek, Berti, Enora, Bertier, Astrid, Besset, Sébastien, Bret, Marlène, Cariou, Alain, Carpentier, Christophe, Chaouch, Oussama, Chariot, Appoline, Charron, Cyril, Charpentier, Julien, Cheurfa, Cherifa, Cholley, Bernard, Clerc, Sébastien, Combes, Alain, Chousterman, Benjamin, Cohen, Yves, Constantin, Jean-Michel, Damoisel, Charles, Darmon, Michael, Degos, Vincent, D’Ableiges, Bertrand De Maupeou, Demeret, Sophie, Montmollin, Etienne De, Demoule, Alexandre, Depret, Francois, Diehl, Jean-Luc, Djibré, Michel, Do, Chung-Hi, Dudoignon, Emmanuel, Duranteau, Jacques, Fartoukh, Muriel, Fieux, Fabienne, Gayat, Etienne, Gennequin, Mael, Guidet, Bertrand, Gutton, Christophe, Hamada, Sophie, Heming, Nicholas, Jouffroy, Romain, Keita-Meyer, Hawa, Langeron, Olivier, Lortat-Jacob, Brice, Marey, Jonathan, Mebazaa, Alexandre, Megarbane, Bruno, Mekontso-Dessap, Armand, Mira, Jean-Paul, Molle, Julie, Mongardon, Nicolas, Montravers, Philippe, Morelot-Panzini, Capucine, Nemlaghi, Safaa, Nguyen, Bao-long, Parrot, Antoine, Pasqualotto, Romain, Peron, Nicolas, Picard, Lucile, de Chambrun, Marc Pineton, Planquette, Benjamin, Plaud, Benoit, Pons, Stéphanie, Quesnel, Christophe, Raphalen, Jean-Herlé, Razazi, Keyvan, Ricard, Jean-Damien, Roche, Anne, Rohaut, Benjamin, Roux, Damien, Savale, Laurent, Sobotka, Jennifer, Teboul, Jean-Louis, Timsit, Jean-François, Voiriot, Guillaume, Weiss, Emmanuel, Wildenberg, Lucille, Zogheib, Elie, Riou, Bruno, Batteux, Frédéric.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327150

ABSTRACT

Importance Information about the severity of Omicron is scarce. Objective To report the respective risk of ICU admission in patients hospitalized with Delta and Omicron variants and to compare the characteristics and disease severity of critically ill patients infected with both variants according to vaccination status. Design Analysis from the APHP database, called Reality, prospectively recording the following information in consecutive patients admitted in the ICU for COVID-19: age, sex, immunosuppression, vaccination, pneumonia, need for invasive mechanical ventilation, time between symptom onset and ICU admission, and in-ICU mortality. Retrospective analysis on an administrative database, “Système d’Information pour le Suivi des Victimes” (SI-VIC), which lists hospitalized COVID-19 patients. Setting 39 hospitals in the Paris area from APHP group. Participants Patients hospitalized from December 1, 2021 to January 18, 2022 for COVID-19. Main outcomes and measures Risk of ICU admission was evaluated in 3761 patients and Omicron cases were compared to Delta cases in the ICU in 888 consecutive patients. Results On January 18, 45% of patients in the ICU and 63.8% of patients in conventional hospital units were infected with the Omicron variant (p < 0.001). The risk of ICU admission with Omicron was reduced by 64% than with Delta (9.3% versus 25.8% of cases, respectively, p < 0.001). In critically ill patients, 400 had the Delta variant, 229 the Omicron variant, 98 had an uninformative variant screening test and 161 did not have information on variant screening test. 747 patients (84.1%) were admitted for pneumonia. Compared to patients infected with Delta, Omicron patients were more vaccinated (p<0.001), even with 3 doses, more immunocompromised (p<0.001), less admitted for pneumonia (p<0.001), especially when vaccinated (62.1% in vaccinated versus 80.7% in unvaccinated, p<0.001), and less invasively ventilated (p=0.02). Similar results were found in the subgroup of pneumonia but Omicron cases were older. Unadjusted in-ICU mortality did not differ between Omicron and Delta cases, neither in the overall population (20.0% versus 27.9%, p = 0.08), nor in patients with pneumonia (31.6% versus 29.7%, respectively) where adjusted in-ICU mortality did not differ according to the variant (HR 1.43 95%CI [0.89;2.29], p=0.14). Conclusion and relevance Compared to the Delta variant, the Omicron variant is less likely to result in ICU admission and less likely to be associated with pneumonia. However, when patients with the Omicron variant are admitted for pneumonia, the severity seems similar to that of patients with the Delta variant, with more immunocompromised and vaccinated patients and no difference in adjusted in-ICU mortality. Further studies are needed to confirm our results.

9.
Ann Intensive Care ; 11(1): 170, 2021 Dec 11.
Article in English | MEDLINE | ID: covidwho-1566528

ABSTRACT

BACKGROUND: Predicting outcomes of critically ill intensive care unit (ICU) patients with coronavirus-19 disease (COVID-19) is a major challenge to avoid futile, and prolonged ICU stays. METHODS: The objective was to develop predictive survival models for patients with COVID-19 after 1-to-2 weeks in ICU. Based on the COVID-ICU cohort, which prospectively collected characteristics, management, and outcomes of critically ill patients with COVID-19. Machine learning was used to develop dynamic, clinically useful models able to predict 90-day mortality using ICU data collected on day (D) 1, D7 or D14. RESULTS: Survival of Severely Ill COVID (SOSIC)-1, SOSIC-7, and SOSIC-14 scores were constructed with 4244, 2877, and 1349 patients, respectively, randomly assigned to development or test datasets. The three models selected 15 ICU-entry variables recorded on D1, D7, or D14. Cardiovascular, renal, and pulmonary functions on prediction D7 or D14 were among the most heavily weighted inputs for both models. For the test dataset, SOSIC-7's area under the ROC curve was slightly higher (0.80 [0.74-0.86]) than those for SOSIC-1 (0.76 [0.71-0.81]) and SOSIC-14 (0.76 [0.68-0.83]). Similarly, SOSIC-1 and SOSIC-7 had excellent calibration curves, with similar Brier scores for the three models. CONCLUSION: The SOSIC scores showed that entering 15 to 27 baseline and dynamic clinical parameters into an automatable XGBoost algorithm can potentially accurately predict the likely 90-day mortality post-ICU admission (sosic.shinyapps.io/shiny). Although external SOSIC-score validation is still needed, it is an additional tool to strengthen decisions about life-sustaining treatments and informing family members of likely prognosis.

11.
Crit Care ; 25(1): 355, 2021 10 09.
Article in English | MEDLINE | ID: covidwho-1463260

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) was frequently used to treat patients with severe coronavirus disease-2019 (COVID-19)-associated acute respiratory distress (ARDS) during the initial outbreak. Care of COVID-19 patients evolved markedly during the second part of 2020. Our objective was to compare the characteristics and outcomes of patients who received ECMO for severe COVID-19 ARDS before or after July 1, 2020. METHODS: We included consecutive adults diagnosed with COVID-19 in Paris-Sorbonne University Hospital Network ICUs, who received ECMO for severe ARDS until January 28, 2021. Characteristics and survival probabilities over time were estimated during the first and second waves. Pre-ECMO risk factors predicting 90-day mortality were assessed using multivariate Cox regression. RESULTS: Characteristics of the 88 and 71 patients admitted, respectively, before and after July 1, 2020, were comparable except for older age, more frequent use of dexamethasone (18% vs. 82%), high-flow nasal oxygenation (19% vs. 82%) and/or non-invasive ventilation (7% vs. 37%) after July 1. Respective estimated probabilities (95% confidence intervals) of 90-day mortality were 36% (27-47%) and 48% (37-60%) during the first and the second periods. After adjusting for confounders, probability of 90-day mortality was significantly higher for patients treated after July 1 (HR 2.27, 95% CI 1.02-5.07). ECMO-related complications did not differ between study periods. CONCLUSIONS: 90-day mortality of ECMO-supported COVID-19-ARDS patients increased significantly after July 1, 2020, and was no longer comparable to that of non-COVID ECMO-treated patients. Failure of prolonged non-invasive oxygenation strategies before intubation and increased lung damage may partly explain this outcome.


Subject(s)
COVID-19/mortality , Extracorporeal Membrane Oxygenation/mortality , Extracorporeal Membrane Oxygenation/trends , Hospitalization/trends , Respiratory Distress Syndrome/mortality , Severity of Illness Index , Adult , COVID-19/therapy , Cohort Studies , Female , Follow-Up Studies , Humans , Intensive Care Units/trends , Male , Middle Aged , Mortality/trends , Paris/epidemiology , Respiratory Distress Syndrome/therapy , Treatment Outcome
12.
Am J Respir Crit Care Med ; 2021 May 26.
Article in English | MEDLINE | ID: covidwho-1416749

ABSTRACT

RATIONALE: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with COVID-19, based on Surviving Sepsis Campaign guidelines. OBJECTIVE: We aimed to determine the prevalence of early bacterial identification in intubated patients with SARS-CoV-2 pneumonia, as compared to influenza pneumonia, and to characterize its microbiology and impact on outcomes. METHODS: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48h were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture, within 48h after intubation, in endotracheal aspirates, bronchoalveolar lavage, blood cultures, or a positive pneumococcal or legionella urinary antigen test. MEASUREMENTS AND MAIN RESULTS: 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia (9.7 vs 33.6%, unadjusted odds ratio (OR) 0.21 (95% confidence interval (CI) 0.15 to 0.30), adjusted OR 0.23 (95% CI 0.16 to 0.33), p<0.0001). Gram-positive cocci were responsible for 58% and 72% of co-infection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57 (95% CI 1.01 to 2.44), p=0.043). However, no significant difference was found in heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of co-infection on mortality was not different between SARS-CoV-2 and influenza patients. CONCLUSIONS: Bacterial identification within 48h after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia. 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/).

14.
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
15.
Blood ; 136(Supplement 1):5-6, 2020.
Article in English | PMC | ID: covidwho-1339021

ABSTRACT

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) characterized by acute pneumonia which may progress to respiratory failure and life-threatening complications, including acute respiratory distress syndrome (ARDS) and multisystem organ failure with fatal outcome. COVID-19 should be regarded as a systemic disease involving multiple systems. COVID-19 is associated with excessive inflammation, platelet activation, endothelial dysfunction, blood coagulation activation and fibrin formation. The development of a screening algorithm for the evaluation of endothelial and blood coagulation activation is an urgent need for the optimisation of the management of the patients with severe COVID-19. To this aim biomarkers of endothelial cell activation and hypercoagulability have central placeAim: The prospective observational monocentric cohort study ROADMAP-COVID-19 study aimed to evaluate the biomarkers of hypercoagulability and endothelial cell activation which they could be used in the development of a screening algorithm in patients with COVID-19Methods: The ROADMAP-COVID-19 study enrolled 90 consecutive patients hospitalized at Tenon University Hospital (AP-HP, Paris) between March 18th and April 30th, 2020 with confirmed SARS-CoV-2 infection admitted to the ICU with clinically deteriorated severe COVID-19 (ICU- group). Patients were assessed upon the first day to the ICU admission. The control group consisted 30 healthy individuals (C-group). All patients and controls were evaluated for, clotting times (PT and aPTT), fibrinogen, D-Dimers, antithrombin (AT), protein C (PC) and protein S (Ps) activity, clotting factors V (FV), VIII (FVIII) and XII (FXII), high molecular weight kininogen (HK), von Willebrand factor (FvW), thrombin generation assay (TG) using TF 20 pM-PPP-Reagent® (Thrombogram-Thrombinoscope from Stago), fibrin monomers (FM), free TFPI and TF activity, thrombomodulin activity (TM), TF expressing microparticles (the ratio TF/TFPI was also calculated) and Heparanase. The IL-6 levels were also measured. All patients hospitalized in conventional medical department or in ICU routinely received thromboprophylaxis with body weight adapted enoxaparin. The ratio of the mean values of each studied biomarker in the ICU and the C-group was calculated. Biomarkers were classified in four clusters (Decrease, Stable, Slight Increase, Moderate Increase and High Increase).Results :The ICU-group consisted of 102 patients;87% of these patients were admitted to the ICU directly from the emergency department. Males were 76 out of 102 patients. Age ranged from 30 to 93 years in the W-group. The changes of the biomarkers in patients with COVID-19 admitted at the ICU as compared to healthy individuals with are shown in Table 1. The ICU patients with COVID-19 were characterized by marked increase of IL-6 followed by increase of heparanase and D-dimers. The PPL-ct showed the most important decrease. Patients showed a significant decrease in FXII levels which was associated with a moderate increase of kininogen levels. The levels of the natural coagulation inhibitors as well as the clotting times (PT and aPTT) did not significantly modify in patients as compared to the controls. The rate of the propagation phase of thrombin generation (MRI) and the Peak of thrombin were significantly decrease and the lag-time was prolonged reflecting the antithrombotic effect of treatment with LMWH. Heparanse, free TFPI, and TM showed moderate or high increase. The decreased Ratio of TF/TFPI indicated that the free TFPI release dominated over the release of soluble TF activity.Conclusion: Patients with severe COVID-19 requiring ICU admission showed inhaled inflammatory reaction, hyperocoagulability and endothelial cell activation whereas platelet activation appeared to be secondary. Among the studied biomarkers the PPL-ct D-dimers and heparanase followed by TFPI, FvW, FM and TM levels appear to be mandatory for hypercoagulability of cellular origin. Interestingly patients with severe OVID-19 showed consumption of FXII indicating intrinsic clotting pathway activation and high levels of HK which also indicates endothelial cell activation. The clinical relevance of these biomarkers for early detection of hypercoagulability of cellular origin in patients with COVID-19 is being evaluated in prospective study.

16.
Ann Intensive Care ; 11(1): 86, 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1247599

ABSTRACT

BACKGROUND: While acute kidney injury (AKI) is frequent in severe SARS-CoV2-related pneumonia ICU patients, few data are still available about its risk factors. METHODS: Retrospective observational study performed in four university affiliated hospitals in Paris. AKI was defined according to the KIDGO guidelines. Factors associated with AKI were picked up using multivariable mixed-effects logistic regression. Independent risk factors of day 28 mortality were assessed using Cox model. RESULTS: 379 patients (median age 62 [53,69], 77% of male) were included. Half of the patients had AKI (n = 195, 52%) including 58 patients (15%) with AKI stage 1, 44 patients (12%) with AKI stage 2, and 93 patients (25% with AKI stage 3). Chronic kidney disease (OR 7.41; 95% CI 2.98-18.4), need for invasive mechanical ventilation at day 1 (OR 4.83; 95% CI 2.26-10.3), need for vasopressors at day 1 (OR 2.1; 95% CI 1.05-4.21) were associated with increased risk of AKI. Day 28 mortality in the cohort was 26.4% and was higher in patients with AKI (37.4 vs. 14.7%, P < 0.001). Neither AKI (HR 1.35; 95% CI 0.78-2.32) nor AKI stage were associated with mortality (HR [95% CI] for stage 1, 2 and 3 when compared to no AKI of, respectively, 1.02 [0.49-2.10], 1.73 [0.81-3.68] and 1.42 [0.78-2.58]). CONCLUSION: In this large cohort of SARS-CoV2-related pneumonia patients admitted to the ICU, AKI was frequent, mostly driven by preexisting chronic kidney disease and life sustaining therapies, with unclear adjusted relationship with day 28 outcome.

17.
J Crit Care ; 64: 199-204, 2021 08.
Article in English | MEDLINE | ID: covidwho-1213340

ABSTRACT

PURPOSE: Studies performed in spontaneously breathing patients with mild to moderate respiratory failure suggested that prone position (PP) in COVID-19 could be beneficial. MATERIALS AND METHODS: Consecutive critically ill patients with COVID-19 were enrolled in four ICUs. PP sessions lasted at least 3 h each and were performed twice daily. A Cox proportional hazard model identified factors associated with the need of intubation. A propensity score overlap weighting analysis was performed to assess the association between spontaneous breathing PP (SBPP) and intubation. RESULTS: Among 379 patients, 40 underwent SBPP. Oxygenation was achieved by high flow nasal canula in all but three patients. Duration of proning was 2.5 [1.6;3.4] days. SBPP was well tolerated hemodynamically, increased PaO2/FiO2 (78 [68;96] versus 63 [53;77] mm Hg, p = 0.004) and PaCO2 (38 [34;43] versus 35 [32;38] mm Hg, p = 0.005). Neither day-28 survival (HR 0.51, 95% CI 0.16-1.16] nor risk of invasive ventilation [sHR 0.96; 95% CI 0.49;1.88] differed between patients who underwent PP and others. CONCLUSIONS: SBPP in COVID-19 is feasible and well tolerated in severely hypoxemic patients. It did not induce any effect on risk of intubation and day-28 mortality.


Subject(s)
COVID-19/complications , Patient Positioning , Prone Position , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , SARS-CoV-2 , Aged , Blood Gas Analysis , Cannula , Female , Hemodynamics , Humans , Intensive Care Units , Male , Middle Aged , Paris/epidemiology , Propensity Score , Retrospective Studies , Survival Analysis
19.
J Clin Med ; 10(6)2021 Mar 23.
Article in English | MEDLINE | ID: covidwho-1154430

ABSTRACT

Angiotensin-converting enzyme 2 (ACE2) receptor of severe acute respiratory syndrome coronavirus 2 is involved in baroreflex control mechanisms. We hypothesize that severe coronavirus infectious disease 2019 (COVID-19) patients may show an alteration in baroreflex-mediated heart rate changes in response to arterial hypotension. A pilot study was conducted to assess the response to hypotension in relation to continuous venovenous hemodiafiltration (CVVHDF) in critically ill patients with PCR-confirmed COVID-19 (from February to April 2020) and in critically ill non-COVID-19 patients with sepsis (from February 2018 to February 2020). The endpoint was a change in the heart rate in response to CVVHDF-induced hypotension. The association between COVID-19 status and heart rate change was estimated using linear regression. The study population included 6 COVID-19 patients (67% men; age 58 (53-64) years) and 12 critically ill non-COVID-19 patients (58% men; age 67 (51-71) years). Baseline characteristics, laboratory findings, hemodynamic parameters, and management before CVVHDF-induced hypotension were similar between the two groups, with the exception of a higher positive end-expiratory pressure and doses of propofol and midazolam administered in COVID-19 patients. Changes in the heart rate were significantly lower in COVID-19 patients as compared to critically ill non-COVID-19 patients (-7 (-9; -2) vs. 2 (2;5) bpm, p = 0.003), while the decrease in mean arterial blood pressure was similar between groups. The COVID-19 status was independently associated with a lower change in the heart rate (-11 (-20; -2) bpm; p = 0.03). Our findings suggest an inappropriate heart rate response to hypotension in severe COVID-19 patients compared to critically ill non-COVID-19 patients.

20.
BMC Pulm Med ; 21(1): 46, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1054817

ABSTRACT

BACKGROUND: Sickle-cell anaemia is a widespread genetic disease prevalent worldwide among African and African-American populations. The pathogenesis is most often revealed by pulmonary conditions, including acute thoracic syndrome, which is affecting the life expectancy of these populations. The global spread of CoV2-SARS infection with a respiratory tropism, endothelial damages and procoagulant status endangers the SCD population. However, with only a few case reports, consequences of the Covid-19 pandemic on SCD population remain poorly known. CASE PRESENTATION: We report a case of a 33-year-old man with a history of homozygous SS homozygous sickle cell anemia who consulted on March 24, 2020 for febrile dyspnea 11 days after the onset of symptoms. A nasopharyngeal swab was positive for SARS-CoV-2. His respiratory status worsened rapidly in the emergency room and then in ICU leading to severe ARDS requiring intubation, curarization, and venovenous ECMO. Hematologically, severe hemolysis associated with major thrombocytopenia without documented spinal cord injury was noted. Several transfusion exchanges are performed. The evolution was finally slowly favorable and led to discharge from the intensive care unit and then from the hospital. CONCLUSIONS: This case recalls the importance of an increased prevention policy against COVID-19among the SCD population. In addition, from a therapeutic point of view, it advocates (1) a high preventive anticoagulation from the outset according to the level of D-dimers (2) the use of venovenous ECMO in this particular case, whereas this technique has had rather disappointing results in acute chest syndromes. (3) Unexpectedly, our patient did not develop pulmonary arterial hypertension (PAH) and acute cor pulmonale (ACP), whereas this is a common feature of ARDS during SCD. These last two observations suggest a different pathophysiology of pulmonary disorders in SCD patients in the case of SARS COv2. It could be associated with marked hypoxemia secondary to pulmonary vascular vasodilation.


Subject(s)
Anemia, Sickle Cell/epidemiology , COVID-19/epidemiology , Extracorporeal Membrane Oxygenation/methods , Respiration, Artificial/methods , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Adult , Anemia, Sickle Cell/therapy , COVID-19/complications , COVID-19/therapy , Humans , Male , Pandemics , Radiography, Thoracic , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy
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