Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
1.
Cell Syst ; 12(8): 780-794.e7, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34139154

RESUMO

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.


Assuntos
Biomarcadores/análise , COVID-19/patologia , Progressão da Doença , Proteoma/fisiologia , Fatores Etários , Contagem de Células Sanguíneas , Gasometria , Ativação Enzimática , Humanos , Inflamação/patologia , Aprendizado de Máquina , Prognóstico , Proteômica , SARS-CoV-2/imunologia
2.
Infection ; 49(4): 757-762, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33825125

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.


Assuntos
COVID-19/imunologia , Monócitos/imunologia , SARS-CoV-2/fisiologia , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/sangue , Idoso , Feminino , Hospitalização , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/biossíntese , Regulação para Cima
3.
Infection ; 49(4): 703-714, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33890243

RESUMO

PURPOSE: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. METHODS: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. RESULTS: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. CONCLUSIONS: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/fisiologia , COVID-19/terapia , Estudos de Coortes , Alemanha/epidemiologia , Hospitalização , Humanos , Hipertensão/complicações , Cinética , Estudos Prospectivos , Respiração Artificial , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Carga Viral , Eliminação de Partículas Virais
4.
Eur J Clin Microbiol Infect Dis ; 40(2): 419-421, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32885292

RESUMO

There is lack of standardization of practices and limited evidence on efficacy and safety of nebulization of antimicrobials. We sought to determine inhalation practices in one tertiary care hospital by performing a cross-sectional survey. Eleven adult ICUs were included in the analysis. Three units followed established protocols. Ventilation circuit filters were exchanged at least daily in all but one units. Dosages of aminoglycosides and CMS depended on indication and unit. Nebulization of antimicrobials was generally regarded as safe and efficacious. Our data indicate that approach to nebulization of antimicrobials may be heterogeneous even in a single center.

5.
EClinicalMedicine ; 28: 100579, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33073217

RESUMO

Background: In face of the Coronavirus Disease (COVID)-19 pandemic, best practice for mechanical ventilation in COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) is intensely debated. Specifically, the rationale for high positive end-expiratory pressure (PEEP) and prone positioning in early COVID-19 ARDS has been questioned. Methods: The first 23 consecutive patients with COVID-19 associated respiratory failure transferred to a single ICU were assessed. Eight were excluded: five were not invasively ventilated and three received veno-venous ECMO support. The remaining 15 were assessed over the first 15 days of mechanical ventilation. Best PEEP was defined by maximal oxygenation and was determined by structured decremental PEEP trials comprising the monitoring of oxygenation, airway pressures and trans-pulmonary pressures. In nine patients the impact of prone positioning on oxygenation was investigated. Additionally, the effects of high PEEP and prone positioning on pulmonary opacities in serial chest x-rays were determined by applying a semiquantitative scoring-system. This investigation is part of the prospective observational PA-COVID-19 study. Findings: Patients responded to initiation of invasive high PEEP ventilation with markedly improved oxygenation, which was accompanied by reduced pulmonary opacities within 6 h of mechanical ventilation. Decremental PEEP trials confirmed the need for high PEEP (17.9 (SD ± 3.9) mbar) for optimal oxygenation, while driving pressures remained low. Prone positioning substantially increased oxygenation (p<0.01). Interpretation: In early COVID-19 ARDS, substantial PEEP values were required for optimizing oxygenation. Pulmonary opacities resolved during mechanical ventilation with high PEEP suggesting recruitment of lung volume. Funding: German Research Foundation, German Federal Ministry of Education and Research.

6.
Cell ; 182(6): 1419-1440.e23, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32810438

RESUMO

Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRhiCD11chi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.


Assuntos
Infecções por Coronavirus/imunologia , Células Mieloides/imunologia , Mielopoese , Pneumonia Viral/imunologia , Adulto , Idoso , Antígenos CD11/genética , Antígenos CD11/metabolismo , COVID-19 , Células Cultivadas , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Feminino , Antígenos HLA-DR/genética , Antígenos HLA-DR/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Células Mieloides/citologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Proteoma/genética , Proteoma/metabolismo , Proteômica , Análise de Célula Única
7.
Trials ; 21(1): 577, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32586396

RESUMO

OBJECTIVES: Approximately 8 - 10 % of COVID-19 patients present with a serious clinical course and need for hospitalization, 8% of hospitalized patients need ICU-treatment. Currently, no causal therapy is available and treatment is purely supportive. The main reason for death in critically ill patients is acute respiratory failure. However, in a number of patients a severe hyperinflammatory response with excessively elevated proinflammatory cytokines causes vasoplegic shock resistant to vasopressor therapy. A new polystyrene-based hemoadsorber (CytoSorb®, Cytosorbents Inc., New Jersey, USA) has been shown to adsorb effectively cytokines and other middle molecular weight toxins this way reducing their blood concentrations. This has been routinely used in clinical practice in the EU for other conditions where a cytokine storm occurs and an observational study has just been completed on COVID-19 patients. We hypothesized that the extracorporeal elimination of cytokines in critically ill COVID-19 patients with suspected hyperinflammation and shock may stabilize hemodynamics and improve outcome. The primary endpoint is time until resolution of vasoplegic shock, which is a well implemented, clinically relevant endpoint in critical care studies. TRIAL DESIGN: Phase IIb, multicenter, prospective, open-label, randomized, 1:1 parallel group pilot study comparing the additional use of "CytoSorb" to standard of care without "CytoSorb". PARTICIPANTS: Patients are recruited from the Intensive Care Units (ICUs) of 7 participating centers in Germany (approximately 10 ICUs). All patients aged 18- 80 with positive polymerase chain reaction (PCR) test for SARS-CoV-2, a C-reactive protein (CRP) ≥ 100 mg/l, a Procalcitonin (PCT) < 2 ng/l, and suspected cytokine storm defined via a vasoplegic shock (Norepinephrine > 0.2 µg/min/kg to achieve a Mean Arterial Pressure ≥ 65mmHg). Patients are included irrespective of indication for renal replacement therapy. Suspected or proven bacterial cause for vasoplegic shock is a contraindication. INTERVENTION AND COMPARATOR: Within 24 hours after meeting the inclusion criteria patients will be randomized to receive either standard of care or standard of care and additional "CytoSorb" therapy via a shaldon catheter for 3-7 days. Filter exchange is done every 24 hours. If patients receive antibiotics, an additional dose of antibiotics is administered after each change of "CytoSorb" filter in order to prevent underdosing due to "CytoSorb" treatment. MAIN OUTCOMES: Primary outcome is time to resolution of vasoplegic shock (defined as no need for vasopressors for at least 8 hours in order to sustain a MAP ≥ 65mmHg) in days. Secondary outcomes are 7 day mortality after fulfilling the inclusion criteria, mortality until hospital discharge, Interleukin-6 (IL-6) measurement on day 1 and 3, need for mechanical ventilation, duration of mechanical ventilation, duration of ICU-stay, catecholamine dose on day 1/2/3 after start of "CytoSorb" and acute kidney injury. RANDOMIZATION: An electronic randomization will be performed using the study software secuTrial® administered by the Clinical Study Center (CSC) of the Charité - Universitätsmedizin Berlin, Germany. Randomization is done in blocks by 4 stratified by including center. BLINDING (MASKING): The trial will be non-blinded for the clinicians and patients. The statistician will receive a blinded data set, so that all analyses will be conducted blinded. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): As this is a pilot study with the goal to examine the feasibility of the study design as well as the intervention effect, no formal sample size calculation was conducted. A total number of approximately 80-100 patients is planned (40-50 patients per group). Safety assessment is done after the inclusion of each 10 patients per randomization group. TRIAL STATUS: Please see the study protocol version from April 24 2020. Recruitment of patients is still pending. TRIAL REGISTRATION: The study was registered on April 27 2020 in the German Registry of Clinical Trials (DRKS) under the number DRKS00021447. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Citocinas/sangue , Hemadsorção , Pneumonia Viral/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Estado Terminal , Citocinas/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Adulto Jovem
8.
Infection ; 48(4): 619-626, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32535877

RESUMO

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. METHODS: Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charité - Universitätsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, and pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up. RESULTS: Outcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional, and health-related quality-of-life assessments at discharge and during follow-up. We developed a scalable dataset to (i) suit national standards of care, (ii) facilitate comprehensive data collection in medical care facilities with varying resources, and (iii) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany. CONCLUSION: We established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00021688).


Assuntos
Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Sistema de Registros , Berlim/epidemiologia , Betacoronavirus , Bancos de Espécimes Biológicos , COVID-19 , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Humanos , Estudos Observacionais como Assunto , Pandemias , Fenótipo , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , SARS-CoV-2 , Fatores de Tempo , Resultado do Tratamento , Organização Mundial da Saúde
9.
Crit Care ; 18(3): R120, 2014 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-24923469

RESUMO

INTRODUCTION: Acute kidney injury (AKI) occurs in 7% of hospitalized and 66% of Intensive Care Unit (ICU) patients. It increases mortality, hospital length of stay, and costs. The aim of this study was to investigate, whether there is an association between adherence to guidelines (standard operating procedures (SOP)) for potentially nephrotoxic antibiotics and the occurrence of AKI. METHODS: This study was carried out as a prospective, clinical, non-interventional, observational study. Data collection was performed over a total of 170 days in three ICUs at Charité - Universitaetsmedizin Berlin. A total of 675 patients were included; 163 of these had therapy with vancomycin, gentamicin, or tobramycin; were >18 years; and treated in the ICU for >24 hours. Patients with an adherence to SOP >70% were classified into the high adherence group (HAG) and patients with an adherence of <70% into the low adherence group (LAG). AKI was defined according to RIFLE criteria. Adherence to SOPs was evaluated by retrospective expert audit. Development of AKI was compared between groups with exact Chi2-test and multivariate logistic regression analysis (two-sided P <0.05). RESULTS: LAG consisted of 75 patients (46%) versus 88 HAG patients (54%). AKI occurred significantly more often in LAG with 36% versus 21% in HAG (P = 0.035). Basic characteristics were comparable, except an increased rate of soft tissue infections in LAG. Multivariate analysis revealed an odds ratio of 2.5-fold for LAG to develop AKI compared with HAG (95% confidence interval 1.195 to 5.124, P = 0.039). CONCLUSION: Low adherence to SOPs for potentially nephrotoxic antibiotics was associated with a higher occurrence of AKI. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54598675. Registered 17 August 2007.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Fidelidade a Diretrizes , Esquema de Medicação , Feminino , Gentamicinas/administração & dosagem , Gentamicinas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Respiração Artificial , Fatores de Tempo , Tobramicina/administração & dosagem , Tobramicina/efeitos adversos , Vancomicina/administração & dosagem , Vancomicina/efeitos adversos
10.
J Crit Care ; 29(3): 340-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24508203

RESUMO

PURPOSE: The purpose of the study is to compare H1N1-induced acute respiratory distress syndrome (ARDS) with ARDS due to other causes of severe community-acquired pneumonia focusing on pulmonary function. MATERIALS AND METHODS: This is a retrospective data analysis of adult ARDS patients between January 2009 and December 2010 in an ARDS referral center. Patient characteristics, severity of illness scores, modalities, and duration of extracorporeal lung support were evaluated as well as intensive care unit stay and survival. Parameters of mechanical ventilation and pulmonary function were analyzed on day of admission and over the consecutive 10 days using a nonparametric analysis of longitudinal data in a 2-factorial design. In a logistic regression analysis, risk factors for extracorporeal lung support were investigated. RESULTS: Twenty-one patients with H1N1-ARDS and 41 with non-H1N1-ARDS were identified. Gas exchange was more severely impaired in patients with H1N1-ARDS over course of time. Extracorporeal membrane oxygenation was more frequently needed in H1N1-ARDS. Despite significantly prolonged weaning off extracorporeal lung support and intensive care unit stay in H1N1 patients, the proportion of survivors did not differ significantly. Only Sepsis-Related Organ Failure Assessment score could be identified as an independent predictor of extracorporeal lung support. CONCLUSIONS: Clinical course of H1N1-ARDS is substantially different from non-H1N1-ARDS. Affected patients may require extensive therapy including extracorporeal lung support in ARDS referral centers.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Pneumonia/etiologia , Síndrome do Desconforto Respiratório/etiologia , Adulto , Infecções Comunitárias Adquiridas/etiologia , Infecções Comunitárias Adquiridas/fisiopatologia , Infecções Comunitárias Adquiridas/terapia , Oxigenação por Membrana Extracorpórea , Feminino , Hospitalização , Humanos , Influenza Humana/fisiopatologia , Influenza Humana/terapia , Unidades de Terapia Intensiva , Pulmão , Masculino , Pessoa de Meia-Idade , Pneumonia/fisiopatologia , Troca Gasosa Pulmonar/fisiologia , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos
11.
Intensive Care Med ; 38(10): 1632-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22836139

RESUMO

PURPOSE: To evaluate whether extracorporeal carbon dioxide removal by means of a pumpless extracorporeal lung-assist (PECLA) device could be an effective and safe alternative to invasive mechanical ventilation in patients with chronic pulmonary disease and acute hypercapnic ventilatory failure not responding to noninvasive ventilation (NIV). METHODS: In this multicentre, retrospective study, 21 PECLA patients were compared with respect to survival and procedural outcomes to 21 matched controls with conventional invasive mechanical ventilation. Matching criteria were underlying diagnosis, age, Simplified Acute Physiology Score II and pH at ICU admission. RESULTS: Of the 21 patients treated with PECLA, 19 (90 %) did not require intubation. Median PaCO(2) levels and pH in arterial blood prior to PECLA were 84.0 mmHg (54.2-131.0) and 7.28 (7.10-7.41), respectively. Within 24 h, median PaCO(2) levels and pH had significantly improved to 52.1 (33.0-70.1; p < 0.001) and 7.44 (7.27-7.56; p < 0.001), respectively. Two major and seven minor bleeding complications related to the device occurred. Further complications were one pseudoaneurysm and one heparin-induced thrombocytopenia type 2. Compared to the matched control group, there was a trend toward a shorter hospital length of stay in the PECLA group (adjusted p = 0.056). There was no group difference in the 28-day (24 % vs. 19 %, adjusted p = 0.845) or 6-month mortality (33 % vs. 33 %). CONCLUSIONS: In this study the use of extracorporeal carbon dioxide removal allowed avoiding intubation and invasive mechanical ventilation in the majority of patients with acute on chronic respiratory failure not responding to NIV. Compared to conventional invasive ventilation, short- and long-term survivals were similar.


Assuntos
Dióxido de Carbono , Circulação Extracorpórea/métodos , Hipercapnia/terapia , Ventilação não Invasiva/métodos , Doença Pulmonar Obstrutiva Crônica/terapia , Respiração Artificial/métodos , Insuficiência Respiratória/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Circulação Extracorpórea/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ventilação não Invasiva/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/complicações , Respiração Artificial/efeitos adversos , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Falha de Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...