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1.
Crit Care ; 26(1): 155, 2022 05 30.
Article in English | MEDLINE | ID: covidwho-1951297

ABSTRACT

BACKGROUND: A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome. METHODS: By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2-negative patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity. RESULTS: At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets-both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide. Moreover patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors. CONCLUSIONS: These data suggest that neutrophil exhaustion may be involved in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome.


Subject(s)
COVID-19 , Community-Acquired Infections , Pneumonia , Aged , Homeostasis , Humans , Inflammation , Longitudinal Studies , Neutrophils/physiology , Pneumonia/pathology , SARS-CoV-2 , Severity of Illness Index
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.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315970

ABSTRACT

Background: Data on incidence, clinical presentation and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. Methods: . Case series of patients with COVID-19 pneumonia admitted to a single ICU in France. All consecutive patients requiring MV with RT-PCR–confirmed SARS-CoV-2 infection between March 12th and April 24 th , 2020 were included. Frequency, clinical characteristics, responsible pathogens and outcomes of VAP were assessed, and compared to an historical cohort of patients with severe influenza-associated pneumonia requiring MV admitted to the same ICU during the preceding three winter seasons. Results: : Among 54 consecutive patients with Covid-19–associated acute respiratory failure requiring MV included (median (IQR) age 48 (42-58) years;74% male;93% requiring venovenous-extracorporeal membrane oxygenation), 46 (85%) developed VAP (median (IQR) MV duration before the first episode, 11 (8-16) days). VAP-causative pathogens were predominantly Enterobacteriaceae (72%), particularly inducible AmpC-cephalosporinase producers (41%), followed by Pseudomonas aeruginosa (35%). VAP recurred in 46 (85%) patients and 17 (31%) died. Most recurrences were relapses (ie, infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Despite a high P. aeruginosa -VAP rate in patients with influenza-associated ARDS, the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups. Conclusions: : Patients with severe Covid-19–associated acute respiratory failure requiring MV had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase–producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296817

ABSTRACT

Background: Emerging data based on analyses of peripheral and pulmonary immune responses to SARS-CoV-2 increasingly suggest that a dysregulated immune response underpins the development of severe disease in COVID-19 patients. Neutrophils are key components of early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought to decipher the role of neutrophil phenotypes, functions, and homeostasis in COVID-19 disease severity and outcome. Methods: This longitudinal study compares study compares peripheral whole-blood neutrophils from 90 COVID-19 ICU patients with those of 22 SARS-CoV-2 – patients hospitalized for severe community-acquired pneumonia (CAP) and 38 healthy controls. We also assessed correlations between these phenotypic and functional indicators and markers of endothelial damage as well as disease severity. Results: At ICU admission, the circulating neutrophils of the COVID-19 patients showed continuous basal hyperactivation not seen in CAP patients, associated with higher circulating levels of soluble E- and P-selectin, which reflect platelet and endothelial activation. Furthermore, COVID-19 patients had expanded aged-angiogenic and reverse transmigrated neutrophil subsets — both involved in endothelial dysfunction and vascular inflammation. Simultaneously, COVID-19 patients had significantly lower levels of neutrophil oxidative burst in response to bacterial formyl peptide, an abnormality that was greater in superinfected than non-superinfected COVID-19 patients. Moreover, patients dying of COVID-19 had significantly higher expansion of aged-angiogenic neutrophil subset and greater impairment of oxidative burst response than survivors. Conclusions: These data suggest that neutrophil exhaustion may play a central role in the pathogenesis of severe COVID-19 and identify angiogenic neutrophils as a potentially harmful subset involved in fatal outcome.

6.
Annales de Dermatologie et de Vénéréologie - FMC ; 1(8, Supplement 1):A156, 2021.
Article in French | ScienceDirect | ID: covidwho-1520910

ABSTRACT

Introduction Le traitement du syndrome d’hypersensibilité médicamenteuse ou drug reaction with eosinophilia and systemic symptoms (DRESS) est difficile. En cas d’atteinte viscérale, une corticothérapie systémique est le plus souvent proposée en première intention malgré l’absence d’essai clinique. En l’absence de réponse, le traitement de deuxième ligne n’est pas codifié. Récemment, le benralizumab un anticorps monoclonal ciblant le récepteur de l’interleukine 5 a été utilisé pour traiter deux patients avec une infection sévère à COVID-19 ayant un DRESS résistant à une corticothérapie à forte dose. Nous rapportons le cas d’un patient infecté par le COVID-19 atteint d’un DRESS avec engagement du pronostic vital traité par benralizumab. Matériel et méthodes Un patient de 43 ans, sans antécédent, hospitalisé pour un syndrome de détresse respiratoire aigu lié à une infection à COVID-19 a présenté un DRESS sévère associant une hyperéosinophilie (6660/mm3), de la fièvre, une polyadénopathie, un exanthème maculopapuleux avec œdème du visage, une insuffisance rénale aiguë, une hépatite et une pneumopathie à éosinophiles. Les médicaments les plus imputables étaient la ciprofloxacine et le céfépime. Le traitement initial de ce DRESS sévère a comporté une corticothérapie locale et systémique. Une aggravation hémodynamique a motivé un traitement par immunoglobulines intraveineuses. Devant une atteinte pluriviscérale associée à une majoration du taux d’éosinophiles (10 000/mm3) et des critères biologiques de syndrome d’activation macrophagique avec engagement du pronostic vital, une injection de benralizumab 30mg en sous-cutanée a été réalisée après concertation multidisciplinaire. Résultats (si adapté) : l’évolution a été très rapidement favorable avec une chute du nombre d’éosinophiles sanguins en 48 heures et une amélioration globale des dysfonctions d’organes et des lésions cutanées. Une deuxième injection de benralizumab a été réalisée quatre semaines plus tard en raison de la réascension modérée des éosinophiles à la décroissance de la corticothérapie générale, sans récidive. Discussion La physiopathologie du DRESS est complexe, elle met en jeu des réponses lymphocytaires T spécifiques et souvent des réactivations virales. Aucune réplication des virus fréquemment rencontrés dans le DRESS (HSV1, HSV2, VZV, CMV, EBV et HHV6) n’a été trouvée chez notre patient. Mais, la mise en évidence d’une réplication du SARS-CoV 2 à distance de l’infection initiale (plus de 60 jours après la 1re PCR SARS-CoV2 positive) pourrait suggérer un rôle potentiel inducteur du SARS-CoV2 dans le DRESS. Le rôle précis des éosinophiles dans la physiopathologie du DRESS n’est pas élucidé, mais l’efficacité et la bonne tolérance du benralizumab chez notre patient plaide en faveur de l’intérêt d’une thérapie anti-IL5 récepteur chez les patients atteints de DRESS sévère corticorésistant ou avec besoin d’une alternative aux corticoïdes systémiques.

7.
Thromb Haemost ; 121(8): 1031-1042, 2021 08.
Article in English | MEDLINE | ID: covidwho-1324458

ABSTRACT

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin-antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p < 0.01) and fibrin formation markers (fibrin monomers, p < 0.001) significantly increased, further resulting in significant decreases in platelet count (p < 0.0001) and fibrinogen level (p < 0.001). PAI-1 levels significantly decreased from baseline to day 7 (p < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 14 nonfatal and 3 fatal bleeding. Additional studies are warranted to determine whether monitoring of thrombin generation and fibrinolysis markers might help to early predict bleeding complications in COVID-19 patients supported by ECMO.


Subject(s)
Blood Coagulation , COVID-19/therapy , Extracorporeal Membrane Oxygenation/adverse effects , Fibrinolysis , Respiratory Distress Syndrome/therapy , Adult , COVID-19/blood , COVID-19/complications , Female , Hemorrhage/etiology , Humans , Male , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/complications , von Willebrand Factor/analysis
9.
Ann Intensive Care ; 10(1): 158, 2020 Nov 23.
Article in English | MEDLINE | ID: covidwho-940755

ABSTRACT

BACKGROUND: The data on incidence, clinical presentation, and outcomes of ventilator-associated pneumonia (VAP) in patients with severe coronavirus disease 2019 (COVID-19) pneumonia requiring mechanical ventilation (MV) are limited. We performed this retrospective cohort study to assess frequency, clinical characteristics, responsible pathogens, and outcomes of VAP in patients COVID-19 pneumonia requiring MV between March 12th and April 24th, 2020 (all had RT-PCR-confirmed SARS-CoV-2 infection). Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring ECMO were compared with an historical cohort of 45 patients with severe influenza-associated ARDS requiring ECMO admitted to the same ICU during the preceding three winter seasons. RESULTS: Among 50 consecutive patients with Covid-19-associated ARDS requiring ECMO included [median (IQR) age 48 (42-56) years; 72% male], 43 (86%) developed VAP [median (IQR) MV duration before the first episode, 10 (8-16) days]. VAP-causative pathogens were predominantly Enterobacteriaceae (70%), particularly inducible AmpC-cephalosporinase producers (40%), followed by Pseudomonas aeruginosa (37%). VAP recurred in 34 (79%) patients and 17 (34%) died. Most recurrences were relapses (i.e., infection with the same pathogen), with a high percentage occurring on adequate antimicrobial treatment. Estimated cumulative incidence of VAP, taking into account death and extubation as competing events, was significantly higher in Covid-19 patients than in influenza patients (p = 0.002). Despite a high P. aeruginosa-VAP rate in patients with influenza-associated ARDS (54%), the pulmonary infection recurrence rate was significantly lower than in Covid-19 patients. Overall mortality was similar for the two groups. CONCLUSIONS: Patients with severe Covid-19-associated ARDS requiring ECMO had a very high late-onset VAP rate. Inducible AmpC-cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa frequently caused VAP, with multiple recurrences and difficulties eradicating the pathogen from the lung.

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