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1.
Trials ; 22(1): 692, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635128

RESUMO

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.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Adulto , Circulação Extracorpórea , Humanos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2
2.
Medicine (Baltimore) ; 100(35): e26164, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477112

RESUMO

ABSTRACT: Patients with systemic rheumatic disease (SRD) share the risks of multi-organ flare-up, cardiovascular diseases, and immunosuppression. Such situations can lead to an acute critical illness. The present study describes the clinical features of SRD patients admitted to the intensive care unit (ICU) and their short- and long- term mortality.We performed a multicentre retrospective study in 10 French ICU in Lyon, France. Inclusion criteria were SRD diagnosis and admission for an acute organ failure. The primary endpoint was ICU mortality.A total of 271 patients were included. SRD included systemic lupus erythematosus (23.2% of included patients), vasculitis (10.7%), systemic sclerosis (10.7%), idiopathic inflammatory myopathy (6.3%), and other connective tissue disorders (rheumatoid arthritis, Sjögren and Sharp syndromes; 50.9%). Initial organ failure(s) were shock (43.5% of included patients), acute kidney injury (30.5%), and acute respiratory failure (23.2%). The cause(s) of ICU admission included sepsis (61.6%), cardiovascular events (33.9%), SRD-flare up (32.8%), and decompensations related to comorbidities (28%). The ICU mortality reached 14.3%. The factors associated with ICU mortality were chronic cardiac failure, invasive ventilation and admission in ICU for another reason than sepsis or SRD flare-up. The median follow-up after ICU discharge was 33.6 months. During follow-up, 109 patients died. The factors associated with long-term mortality included age, Charlson comorbidity index, and ICU admission for sepsis or SRD flare-up.The ICU mortality of patients with SRD was low. Sepsis was the first cause of admission. Cardiovascular events and comorbidities negatively impacted ICU mortality. Admission for sepsis or SRD flare-up exerted a negative effect on the long-term outcome.


Assuntos
Prognóstico , Doenças Reumáticas/complicações , Idoso , Idoso de 80 Anos ou mais , Estado Terminal/epidemiologia , Estado Terminal/mortalidade , Feminino , França , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/mortalidade
3.
Intensive Care Med Exp ; 9(1): 46, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505190

RESUMO

BACKGROUND: Personalizing mechanical ventilation requires the development of reliable bedside monitoring techniques. The multiple-breaths nitrogen washin-washout (MBNW) technique is currently available to measure end-expiratory lung volume (EELVMBNW), but the precision of the technique may be poor, with percentage errors ranging from 28 to 57%. The primary aim of the study was to evaluate the reliability of a novel MBNW bedside system using fast mainstream sensors to assess EELV in an experimental acute respiratory distress syndrome (ARDS) model, using computed tomography (CT) as the gold standard. The secondary aims of the study were: (1) to evaluate trending ability of the novel system to assess EELV; (2) to evaluate the reliability of estimated alveolar recruitment induced by positive end-expiratory pressure (PEEP) changes computed from EELVMBNW, using CT as the gold standard. RESULTS: Seven pigs were studied in 6 experimental conditions: at baseline, after experimental ARDS and during a decremental PEEP trial at PEEP 16, 12, 6 and 2 cmH2O. EELV was computed at each PEEP step by both the MBNW technique (EELVMBNW) and CT (EELVCT). Repeatability was assessed by performing replicate measurements. Alveolar recruitment between two consecutive PEEP levels after lung injury was measured with CT (VrecCT), and computed from EELV measurements (VrecMBNW) as ΔEELV minus the product of ΔPEEP by static compliance. EELVMBNW and EELVCT were significantly correlated (R2 = 0.97). An acceptable non-constant bias between methods was identified, slightly decreasing toward more negative values as EELV increased. The conversion equation between EELVMBNW and EELVCT was: EELVMBNW = 0.92 × EELVCT + 36. The 95% prediction interval of the bias amounted to ± 86 mL and the percentage error between both methods amounted to 13.7%. The median least significant change between repeated measurements amounted to 8% [CI95%: 4-10%]. EELVMBNW adequately tracked EELVCT changes over time (concordance rate amounting to 100% [CI95%: 87%-100%] and angular bias amounting to - 2° ± 10°). VrecMBNW and VrecCT were significantly correlated (R2 = 0.92). A non-constant bias between methods was identified, slightly increasing toward more positive values as Vrec increased. CONCLUSIONS: We report a new bedside MBNW technique that reliably assesses EELV in an experimental ARDS model with high precision and excellent trending ability.

5.
J Exp Med ; 218(10)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34357402

RESUMO

IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3-dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α2 levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.


Assuntos
Autoanticorpos/imunologia , COVID-19/imunologia , Interferon Tipo I/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Animais , Antivirais/imunologia , Antivirais/farmacologia , Autoanticorpos/sangue , COVID-19/sangue , COVID-19/virologia , Chlorocebus aethiops , Feminino , Humanos , Interferon Tipo I/farmacologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/imunologia , Cavidade Nasal/virologia , Estudos Prospectivos , SARS-CoV-2/fisiologia , Células Vero , Carga Viral/efeitos dos fármacos , Carga Viral/imunologia , Replicação Viral/efeitos dos fármacos , Replicação Viral/imunologia
6.
BMJ Open ; 11(8): e048187, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408046

RESUMO

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.


Assuntos
COVID-19 , Pneumonia , Adulto , Antibacterianos/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Reação em Cadeia da Polimerase Multiplex , Pneumonia/tratamento farmacológico , Pró-Calcitonina
7.
Clin Transl Immunology ; 10(8): e1327, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34429968

RESUMO

Objectives: Impairment of type I interferon (IFN-I) immunity has been reported in critically ill COVID-19 patients. This defect can be explained in a subset of patients by the presence of circulating autoantibodies (auto-Abs) against IFN-I. We set out to improve the detection and the quantification of IFN-I auto-Abs in a cohort of critically ill COVID-19 patients, in order to better evaluate the prevalence of these Abs as the pandemic progresses, and how they correlate with the clinical course of the disease. Methods: The concentration of anti-IFN-α2 Abs was determined in the serum of 84 critically ill COVID-19 patients who were admitted to ICU in Hospices Civils de Lyon, France, using a commercially available kit (Thermo Fisher, Catalog #BMS217). Results: A total of 21 of 84 (25%) critically ill COVID-19 patients had circulating anti-IFN-α2 Abs above cut-off (> 34 ng mL-1). Among them, 15 of 21 had Abs with neutralising activity against IFN-α2, that is 15 of 84 (18%) critically ill patients. In addition, we noticed an impairment of the IFN-I response in the majority of patients with neutralising anti-IFN-α2 Abs. There was no significant difference in the clinical characteristics or outcome of with or without neutralising anti-IFN-α2 auto-Abs. We detected anti-IFN-α2 auto-Abs in COVID-19 patients' sera throughout their ICU stay. Finally, we also found auto-Abs against multiple subtypes of IFN-I including IFN-ω. Conclusions: We reported that 18% of critically ill COVID-19 patients were positive for IFN-I auto-Abs, whereas all mild COVID-19 patients were negative, confirming that the presence of these antibodies is associated with a higher risk of developing a critical COVID-19 form.

8.
Crit Care ; 25(1): 248, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266454

RESUMO

BACKGROUND: Differences in physiology of ARDS have been described between COVID-19 and non-COVID-19 patients. This study aimed to compare initial values and longitudinal changes in respiratory system compliance (CRS), oxygenation parameters and ventilatory ratio (VR) in patients with COVID-19 and non-COVID-19 pulmonary ARDS matched on oxygenation. METHODS: 135 patients with COVID-19 ARDS from two centers were included in a physiological study; 767 non-COVID-19 ARDS from a clinical trial were used for the purpose of at least 1:2 matching. A propensity-matching was based on age, severity score, oxygenation, positive end-expiratory pressure (PEEP) and pulmonary cause of ARDS and allowed to include 112 COVID-19 and 198 non-COVID pulmonary ARDS. RESULTS: The two groups were similar on initial oxygenation. COVID-19 patients had a higher body mass index, higher CRS at day 1 (median [IQR], 35 [28-44] vs 32 [26-38] ml cmH2O-1, p = 0.037). At day 1, CRS was correlated with oxygenation only in non-COVID-19 patients; 61.6% and 68.2% of COVID-19 and non-COVID-19 pulmonary ARDS were still ventilated at day 7 (p = 0.241). Oxygenation became lower in COVID-19 than in non-COVID-19 patients at days 3 and 7, while CRS became similar. VR was lower at day 1 in COVID-19 than in non-COVID-19 patients but increased from day 1 to 7 only in COVID-19 patients. VR was higher at days 1, 3 and 7 in the COVID-19 patients ventilated using heat and moisture exchangers compared to heated humidifiers. After adjustment on PaO2/FiO2, PEEP and humidification device, CRS and VR were found not different between COVID-19 and non-COVID-19 patients at day 7. Day-28 mortality did not differ between COVID-19 and non-COVID-19 patients (25.9% and 23.7%, respectively, p = 0.666). CONCLUSIONS: For a similar initial oxygenation, COVID-19 ARDS initially differs from classical ARDS by a higher CRS, dissociated from oxygenation. CRS become similar for patients remaining on mechanical ventilation during the first week of evolution, but oxygenation becomes lower in COVID-19 patients. TRIAL REGISTRATION: clinicaltrials.gov NCT04385004.


Assuntos
COVID-19/terapia , Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/terapia , Idoso , Gasometria , Índice de Massa Corporal , COVID-19/fisiopatologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Troca Gasosa Pulmonar/fisiologia , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/fisiopatologia , Testes de Função Respiratória , Mecânica Respiratória/fisiologia , SARS-CoV-2
9.
Ann Intensive Care ; 11(1): 95, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34125314

RESUMO

BACKGROUND: Hemodynamic instability is a frequent complication of continuous renal replacement therapy (CRRT). Postural tests (i.e., passive leg raising in the supine position or Trendelenburg maneuver in the prone position) combined with measurement of cardiac output are highly reliable to identify preload-dependence and may provide new insights into the mechanisms involved in hemodynamic instability related to CRRT (HIRRT). We aimed to assess the prevalence and risk factors of HIRRT associated with preload-dependence in ICU patients. We conducted a single-center prospective observational cohort study in ICU patients with acute kidney injury KDIGO 3, started on CRRT in the last 24 h, and monitored with a PiCCO® device. The primary endpoint was the rate of HIRRT episodes associated with preload-dependence during the first 7 days after inclusion. HIRRT was defined as the occurrence of a mean arterial pressure below 65 mmHg requiring therapeutic intervention. Preload-dependence was assessed by postural tests every 4 h, and during each HIRRT episode. Data are expressed in median [1st quartile-3rd quartile], unless stated otherwise. RESULTS: 42 patients (62% male, age 69 [59-77] year, SAPS-2 65 [49-76]) were included 6 [1-16] h after CRRT initiation and studied continuously for 121 [60-147] h. A median of 5 [3-8] HIRRT episodes occurred per patient, for a pooled total of 243 episodes. 131 episodes (54% [CI95% 48-60%]) were associated with preload-dependence, 108 (44%, [CI95% 38-51%]) without preload-dependence, and 4 were unclassified. Multivariate analysis (using variables collected prior to HIRRT) identified the following variables as risk factors for the occurrence of HIRRT associated with preload-dependence: preload-dependence before HIRRT [odds ratio (OR) = 3.82, p < 0.001], delay since last HIRRT episode > 8 h (OR = 0.56, p < 0.05), lactate (OR = 1.21 per 1-mmol L-1 increase, p < 0.05), cardiac index (OR = 0.47 per 1-L min-1 m-2 increase, p < 0.001) and SOFA at ICU admission (OR = 0.91 per 1-point increase, p < 0.001). None of the CRRT settings was identified as risk factor for HIRRT. CONCLUSIONS: In this single-center study, HIRRT associated with preload-dependence was slightly more frequent than HIRRT without preload-dependence in ICU patients undergoing CRRT. Testing for preload-dependence could help avoiding unnecessary decrease of fluid removal in preload-independent HIRRT during CRRT.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34048876

RESUMO

OBJECTIVES: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-ß-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support. METHODS: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely. RESULTS: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-ß-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-ß-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms. CONCLUSION: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-ß-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens.

11.
Sci Immunol ; 6(59)2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34035116

RESUMO

Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vß21.3 T cell receptor ß chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vß21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vß21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , COVID-19/patologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , Adulto , Criança , Pré-Escolar , Citocinas/sangue , Antígenos HLA-DR/imunologia , Humanos , Ativação Linfocitária/imunologia , SARS-CoV-2/imunologia
12.
Ann Intensive Care ; 11(1): 38, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33655452

RESUMO

BACKGROUND: We describe a frugal approach (focusing on needs, performance, and costs) to manage a massive influx of COVID-19 patients with acute hypoxemic respiratory failure (AHRF) using the Boussignac valve protected by a filter ("Filter Frugal CPAP", FF-CPAP) in and out the ICU. METHODS: (1) A bench study measured the impact of two filters with different mechanical properties on CPAP performances, and pressures were also measured in patients. (2) Non-ICU healthcare staff working in COVID-19 intermediate care units were trained with a video tutorial posted on a massive open online course. (3) A clinical study assessed the feasibility and safety of using FF-CPAP to maintain oxygenation and manage patients out of the ICU during a massive outbreak. RESULTS: Bench assessments showed that adding a filter did not affect the effective pressure delivered to the patient. The resistive load induced by the filter variably increased the simulated patient's work of breathing (6-34%) needed to sustain the tidal volume, depending on the filter's resistance, respiratory mechanics and basal inspiratory effort. In patients, FF-CPAP achieved pressures similar to those obtained on the bench. The massive training tool provided precious information on the use of Boussignac FF-CPAP on COVID-19 patients. Then 85 COVID-19 patients with ICU admission criteria over a 1-month period were studied upon FF-CPAP initiation for AHRF. FF-CPAP significantly decreased respiratory rate and increased SpO2. Thirty-six (43%) patients presented with respiratory indications for intubation prior to FF-CPAP initiation, and 13 (36%) of them improved without intubation. Overall, 31 patients (36%) improved with FF-CPAP alone and 17 patients (20%) did not require ICU admission. Patients with a respiratory rate > 32 breaths/min upon FF-CPAP initiation had a higher cumulative probability of intubation (p < 0.001 by log-rank test). CONCLUSION: Adding a filter to the Boussignac valve does not affect the delivered pressure but may variably increase the resistive load depending on the filter used. Clinical assessment suggests that FF-CPAP is a frugal solution to provide a ventilatory support and improve oxygenation to numerous patients suffering from AHRF in the context of a massive outbreak.

14.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33536313

RESUMO

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10-4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10-3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.


Assuntos
COVID-19/mortalidade , Modelos Teóricos , Nasofaringe/virologia , RNA Viral/análise , SARS-CoV-2/isolamento & purificação , Carga Viral , Idoso , Anticorpos Antivirais/sangue , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Feminino , França/epidemiologia , Hospitalização , Humanos , Cinética , Masculino , Prognóstico , Estudos Prospectivos , RNA Viral/genética , Fatores de Risco , SARS-CoV-2/genética , Taxa de Sobrevida
16.
Med Mycol ; 59(1): 110-114, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-32914189

RESUMO

Occurrence of putative invasive pulmonary aspergillosis was screened in 153 consecutive adult intensive care unit (ICU) patients with respiratory samples addressed for mycological diagnosis during a 6-week period at the emergence of coronavirus disease 2019 (COVID-19) pandemic. Positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) was observed for 106 patients (69.3%). Nineteen of them (17.9%) with positive Aspergillus results were considered as having putative invasive pulmonary aspergillosis. These observations underline the risk of pulmonary aspergillosis in COVID-19 patients, even in patients not previously known to be immunosuppressed, advocating active search for Aspergillus infection and prompt antifungal treatment. Standardized surveillance protocols and updated definitions for ICU putative invasive pulmonary aspergillosis are needed. LAY ABSTRACT: Adult ICU patients with respiratory samples addressed for mycological diagnosis were screened during the emergence of COVID-19 pandemic. Positive SARS-CoV-2 PCR was observed for 106 patients, nineteen of them (17.9%) having aspergillosis. This underlines the risk of aspergillosis in COVID-19 patients.


Assuntos
COVID-19/complicações , Estado Terminal , Aspergilose Pulmonar Invasiva/etiologia , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade
17.
Ann Am Thorac Soc ; 18(5): 857-864, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33112644

RESUMO

Rationale: Clinicians commonly use short-term physiologic markers to assess the benefit of ventilator adjustments. Improved arterial oxygen tension/pressure (PaO2)/fraction of inspired oxygen (FiO2) after ventilator adjustment in acute respiratory distress syndrome is associated with lower mortality. However, as driving pressure (ΔP) reflects lung stress and strain, changes in ΔP may more accurately reflect benefits or harms of ventilator adjustments compared with changes in oxygenation.Objectives: We aimed to compare the association between mortality and the changes in PaO2/FiO2 and ΔP following protocolized ventilator changes.Methods: We assessed associations between mortality and changes in PaO2/FiO2 (ΔPaO2/FiO2) and ΔP (ΔΔP) after postrandomization positive end-expiratory pressure (PEEP) and tidal volume adjustment in reanalyses of the ALVEOLI (Assessment of Low Tidal Volume and Elevated End-Expiratory Volume to Obviate Lung Injury) and ExPress (Expiratory Pressure) trials. We included subjects with available pre- and postintervention PaO2/FiO2 and ΔP (372 in ALVEOLI and 596 in ExPress). In each separate trial cohort, we performed multivariable Cox regression testing the association between ΔPaO2/FiO2 and ΔΔP with mortality.Results: In ALVEOLI, when analyzed as separate variables, ΔPaO2/FiO2 was associated with mortality only in subjects in whom PEEP increased, whereas ΔΔP was associated with mortality irrespective of direction of PEEP change. When modeled together, improved ΔPaO2/FiO2 was not associated with mortality, whereas ΔΔP remained associated with mortality (adjusted hazard ratio [aHR], 1.50 per 5 cm H2O increase; 95% confidence interval [95% CI], 1.21-1.85). When modeled together in ExPress, ΔΔP (aHR, 1.42; 95% CI, 1.14-1.78) was more strongly associated with mortality than ΔPaO2/FiO2 (aHR, 0.95 per 25 mm Hg increase; 95% CI, 0.90-1.00).Conclusions: Reduced ΔP following protocolized ventilator changes was more strongly and consistently associated with lower mortality than was increased PaO2/FiO2, making ΔΔP more informative about benefit from ventilator adjustments. Our results reinforce the primacy of ΔP, rather than oxygenation, as the key variable associated with outcome.

18.
Eur J Immunol ; 51(4): 989-994, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33314090

RESUMO

Low concentrations of type-I interferon (IFN) in blood seem to be associated with more severe forms of Coronavirus disease 2019 (COVID-19). However, following the type-I interferon response (IR) in early stage disease is a major challenge. We evaluated detection of a molecular interferon signature on a FilmArray® system, which includes PCR assays for four interferon stimulated genes. We analyzed three types of patient populations: (i) children admitted to a pediatric emergency unit for fever and suspected infection, (ii) ICU-admitted patients with severe COVID-19, and (iii) healthcare workers with mild COVID-19. The results were compared to the reference tools, that is, molecular signature assessed with Nanostring® and IFN-α2 quantification by SIMOA® (Single MOlecule Array). A strong correlation was observed between the IR measured by the FilmArray®, Nanostring®, and SIMOA® platforms (r-Spearman 0.996 and 0.838, respectively). The FilmArray® panel could be used in the COVID-19 pandemic to evaluate the IR in 45-min with 2 min hand-on-time at hospitalization and to monitor the IR in future clinical trials.


Assuntos
COVID-19/sangue , Interferon-alfa/sangue , Reação em Cadeia da Polimerase/métodos , SARS-CoV-2/imunologia , Adulto , Idoso , COVID-19/imunologia , Criança , Feminino , Pessoal de Saúde , Humanos , Interferon Tipo I/sangue , Interferon Tipo I/genética , Interferon-alfa/genética , Masculino
19.
Crit Care ; 24(1): 672, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267904

RESUMO

BACKGROUND: There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists. METHODS: We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients' characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD). RESULTS: A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p < 0.001). High inter-intensivist variability did not change with ADs (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain. CONCLUSIONS: ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist's decision took priority. Further research is needed to improve the matching of the physicians' decision with the patient's wishes. Trial registration ClinicalTrials.gov Identifier: NCT03013530. Registered 6 January 2017; https://clinicaltrials.gov/ct2/show/NCT03013530 .

20.
Ann Intensive Care ; 10(1): 166, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296045

RESUMO

BACKGROUND: Intensive Care Units (ICU) have sometimes been overwhelmed by the surge of COVID-19 patients. Extending ICU capacity can be limited by the lack of air and oxygen pressure sources available. Transport ventilators requiring only one O2 source may be used in such places. OBJECTIVE: To evaluate the performances of four transport ventilators and an ICU ventilator in simulated severe respiratory conditions. MATERIALS AND METHODS: Two pneumatic transport ventilators, (Oxylog 3000, Draeger; Osiris 3, Air Liquide Medical Systems), two turbine transport ventilators (Elisee 350, ResMed; Monnal T60, Air Liquide Medical Systems) and an ICU ventilator (Engström Carestation-GE Healthcare) were evaluated on a Michigan test lung. We tested each ventilator with different set volumes (Vtset = 350, 450, 550 ml) and compliances (20 or 50 ml/cmH2O) and a resistance of 15 cmH2O/l/s based on values described in COVID-19 Acute Respiratory Distress Syndrome. Volume error (percentage of Vtset) with P0.1 of 4 cmH2O and trigger delay during assist-control ventilation simulating spontaneous breathing activity with P0.1 of 4 cmH2O and 8 cmH2O were measured. RESULTS: Grouping all conditions, the volume error was 2.9 ± 2.2% for Engström Carestation; 3.6 ± 3.9% for Osiris 3; 2.5 ± 2.1% for Oxylog 3000; 5.4 ± 2.7% for Monnal T60 and 8.8 ± 4.8% for Elisee 350. Grouping all conditions (P0.1 of 4 cmH2O and 8 cmH2O), trigger delay was 50 ± 11 ms, 71 ± 8 ms, 132 ± 22 ms, 60 ± 12 and 67 ± 6 ms for Engström Carestation, Osiris 3, Oxylog 3000, Monnal T60 and Elisee 350, respectively. CONCLUSIONS: In surge situations such as COVID-19 pandemic, transport ventilators may be used to accurately control delivered volumes in locations, where only oxygen pressure supply is available. Performances regarding triggering function are acceptable for three out of the four transport ventilators tested.

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