RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed.
Assuntos
COVID-19 , Unidades de Terapia Intensiva , Tempo de Internação , Respiração Artificial , Encurtamento do Telômero , Humanos , Masculino , COVID-19/terapia , COVID-19/complicações , Feminino , Pessoa de Meia-Idade , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Encurtamento do Telômero/fisiologia , Tempo de Internação/estatística & dados numéricos , Idoso , Estudos Longitudinais , SARS-CoV-2RESUMO
Increasing age is associated with severity and higher mortality of COVID-19. Telomere shortening is associated with higher risk of infections and may be used to identify those patients who are more likely to die. We evaluated the association between relative telomere length (RTL) and COVID-19 mortality. RTL was measured in patients hospitalized because of COVID-19. We used Kaplan-Meier method to analyze survival probabilities, and Cox regression to investigate the association between RTL and mortality (30 and 90 days). Six hundred and eight patients were included in the analysis (mean age =72.5 years, 41.1% women, and 53.8% Caucasic). During the study period, 75 people died from COVID-19 and 533 survived. Lower RTL was associated with a higher risk of death in women either at 30 (adjusted hazard ratio [HR] (aHR) = 3.33; 95% confidence interval [CI] = 1.05-10.00; p = 0.040) and at 90 days (aHR = 3.57; 95%CI = 1.23-11.11; p = 0.019). Lower RTL was associated with a higher risk of dying of COVID-19 in women. This finding suggests that RTL has an essential role in the prognosis of this subset of the population.
Assuntos
COVID-19 , Caracteres Sexuais , Humanos , Masculino , Feminino , Idoso , Prognóstico , Encurtamento do Telômero , TelômeroRESUMO
The usefulness of ultrasound for chest exploration was described in 1968. It was not until the 1990s, when its use became widespread in Intensive Care Units as a diagnostic, monitoring and procedural guide tool. The fact that it is a non-invasive tool, accessible at the bedside, with a sensitivity and specificity close to computerized tomography (CT) and with a short learning curve, have made it a mandatory technique in the management of critically ill patients. It is essential to know that there are different air/fluid ratio generated by different pathologies that gives rise to one echographic pattern or another. The identification of these patterns together with the clinical information will allow to make an accurate diagnosis in most settings of respiratory failure. Likewise, we must not forget the importance of evaluating diaphragmatic function by ultrasound during weaning from mechanical ventilation.
Assuntos
Respiração Artificial , Insuficiência Respiratória , Humanos , Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Diafragma/diagnóstico por imagemRESUMO
Comprehensive ultrasound assessment has become an essential tool to facilitate the diagnosis and therapeutic management of critically ill patients with acute respiratory failure (ARF). There is evidence supporting the use of ultrasound for the diagnosis of pneumothorax, acute respiratory distress syndrome, cardiogenic pulmonary edema, pneumonia and acute pulmonary thromboembolism, and in patients with COVID-19. In addition, in recent years, the use of ultrasound to evaluate responses to treatment in critically ill patients with ARF has been developed, providing a noninvasive tool for titrating positive end-expiratory pressure, monitoring recruitment maneuvers and response to prone position, as well as for facilitating weaning from mechanical ventilation. The objective of this review is to summarize the basic concepts on the utility of ultrasound in the diagnosis and monitoring of critically ill patients with ARF.
Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Humanos , Respiração Artificial , Estado Terminal , Desmame do Respirador , COVID-19/complicações , COVID-19/diagnóstico por imagem , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/diagnóstico por imagem , Insuficiência Respiratória/terapiaRESUMO
Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and Methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.
Assuntos
COVID-19 , Estudos Transversais , Citocinas , Progressão da Doença , Feminino , Humanos , Cinurenina , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Triptofano/metabolismoRESUMO
BACKGROUND: MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to analyze the plasma miRNA profile at COVID-19 onset to identify miRNAs as early prognostic biomarkers of severity and survival. METHODS AND RESULTS: Plasma miRNome of 96 COVID-19 patients that developed asymptomatic/mild, moderate and severe disease was sequenced together with a group of healthy controls. Plasma immune-related biomarkers were also assessed. COVID-19 patients showed 200 significant differentially expressed (SDE) miRNAs concerning healthy controls, with upregulated putative targets of SARS-CoV-2, and inflammatory miRNAs. Among COVID-19 patients, 75 SDE miRNAs were observed in asymptomatic/mild compared to symptomatic patients, which were involved in platelet aggregation and cytokine pathways, among others. Moreover, 137 SDE miRNAs were identified between severe and moderate patients, where miRNAs targeting the SARS CoV-2 genome were the most strongly disrupted. Finally, we constructed a mortality predictive risk score (miRNA-MRS) with ten miRNAs. Patients with higher values had a higher risk of 90-days mortality (hazard ratio = 4.60; p-value < 0.001). Besides, the discriminant power of miRNA-MRS was significantly higher than the observed for age and gender (AUROC = 0.970 vs. 0.881; p = 0.042). CONCLUSIONS: SARS-CoV-2 infection deeply disturbs the plasma miRNome from an early stage of COVID-19, making miRNAs highly valuable as early predictors of severity and mortality.
Assuntos
COVID-19 , MicroRNAs , Biomarcadores , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , SARS-CoV-2RESUMO
Background: The link between coagulation system disorders and COVID-19 has not yet been fully elucidated. Aim: Evaluating the association of non-previously reported coagulation proteins with COVID-19 severity and mortality. Design: Cross-sectional study of 134 COVID-19 patients recruited at admission and classified according to the highest COVID-19 severity reached (asymptomatic/mild, moderate, or severe) and 16 healthy control individuals. Methods: Coagulation proteins levels (antithrombin, prothrombin, factor_XI, factor_XII, and factor_XIII) and CRP were measured in plasma by the ProcartaPlex Panel (Invitrogen) multiplex immunoassay upon diagnosis. Results: We found higher levels of antithrombin, prothrombin, factor XI, factor XII, and factor XIII in asymptomatic/mild and moderate COVID-19 patients compared to healthy individuals. Interestingly, decreased levels of antithrombin and factors XI, XII, and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death. Conclusion: COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might "paradoxically" imply a higher risk of progression to severe disease and COVID-19-related mortality.
RESUMO
BACKGROUND: Information is lacking regarding long-term survival and predictive factors for mortality in patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) and undergoing invasive mechanical ventilation. We aimed to estimate 180-day mortality of patients with COVID-19 requiring invasive ventilation, and to develop a predictive model for long-term mortality. METHODS: Retrospective, multicentre, national cohort study between March 8 and April 30, 2020 in 16 intensive care units (ICU) in Spain. Participants were consecutive adults who received invasive mechanical ventilation for COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected in positive testing of a nasopharyngeal sample and confirmed by real time reverse-transcriptase polymerase chain reaction (rt-PCR). The primary outcomes was 180-day survival after hospital admission. Secondary outcomes were length of ICU and hospital stay, and ICU and in-hospital mortality. A predictive model was developed to estimate the probability of 180-day mortality. RESULTS: 868 patients were included (median age, 64 years [interquartile range [IQR], 56-71 years]; 72% male). Severity at ICU admission, estimated by SAPS3, was 56 points [IQR 50-63]. Prior to intubation, 26% received some type of noninvasive respiratory support. The unadjusted overall 180-day survival rates was 59% (95% CI 56-62%). The predictive factors measured during ICU stay, and associated with 180-day mortality were: age [Odds Ratio [OR] per 1-year increase 1.051, 95% CI 1.033-1.068)), SAPS3 (OR per 1-point increase 1.027, 95% CI 1.011-1.044), diabetes (OR 1.546, 95% CI 1.085-2.204), neutrophils to lymphocytes ratio (OR per 1-unit increase 1.008, 95% CI 1.001-1.016), failed attempt of noninvasive positive pressure ventilation prior to orotracheal intubation (OR 1.878 (95% CI 1.124-3.140), use of selective digestive decontamination strategy during ICU stay (OR 0.590 (95% CI 0.358-0.972) and administration of low dosage of corticosteroids (methylprednisolone 1 mg/kg) (OR 2.042 (95% CI 1.205-3.460). CONCLUSION: The long-term survival of mechanically ventilated patients with severe COVID-19 reaches more than 50% and may help to provide individualized risk stratification and potential treatments. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04379258. Registered 10 April 2020 (retrospectively registered).
RESUMO
La utilidad de la ultrasonografía para la exploración del tórax fue descrita en 1968. No es hasta la década de los 90 cuando se generaliza su uso en las unidades de cuidados intensivos como una herramienta diagnóstica, de seguimiento y guía en procedimientos invasivos. Que sea una herramienta no invasiva, accesible a pie de cama, con una sensibilidad y especificidad cercanas a la tomografía computarizada (TC) y con una curva de aprendizaje corta, la ha convertido en una técnica de uso obligado en el manejo del paciente crítico. Es fundamental conocer que la distinta relación aire/fluido que generan las distintas patologías pulmonares da lugar a distintos patrones ecográficos. La identificación de estos patrones junto con la información clínica nos permitirá hacer un diagnóstico acertado en la mayor parte de causas de insuficiencia respiratoria. Asimismo, no debemos olvidar la importancia de la evaluación de la función diafragmática mediante ecografía durante la desconexión de la ventilación mecánica. (AU)
The usefulness of ultrasound for chest exploration was described in 1968. It was not until the 1990s, when its use became widespread in Intensive Care Units as a diagnostic, monitoring and procedural guide tool. The fact that it is a non-invasive tool, accessible at the bedside, with a sensitivity and specificity close to computerized tomography (CT) and with a short learning curve, have made it a mandatory technique in the management of critically ill patients. It is essential to know that there are different air/fluid ratio generated by different pathologies that gives rise to one echographic pattern or another. The identification of these patterns together with the clinical information will allow to make an accurate diagnosis in most settings of respiratory failure. Likewise, we must not forget the importance of evaluating diaphragmatic function by ultrasound during weaning from mechanical ventilation. (AU)
Assuntos
Humanos , Ultrassonografia/métodos , Unidades de Terapia Intensiva , Ultrassonografia/história , Insuficiência Respiratória/diagnóstico por imagem , Cuidados CríticosRESUMO
En el presente estudio se determino la incidencia de las discrepancias sérico-globulares en pacientes del grupo sanguíneo "A" con leucemia mieloide aguda de novo del Servicio de Hematología del Hospital Nacional Edgardo Rebagliati Matins durante el periodo 2011. Se presentaron un total de 20 pacientes con diagnostico de leucemia mieloide aguda de los cuales 13 fueron del grupo sanguíneo "O", 01 era de grupo sanguíneo "B" y 06 del grupo sanguíneo "A". Se confirmo el grupo sanguíneo en tubo (sérico-globular) a los pacientes del grupo sanguíneo "A", de los cuales cinco de ellos presento una lectura de 4+ (cuatro cruces) en la prueba globular y no se encontró discrepancia con la prueba sérica. Solo un paciente de sexo masculino presento una lectura de 2+ (dos cruces) en la prueba globular y la prueba sérica dio una lectura de 4+. Además se recolectaron los informes del cariotipo de cada paciente, cuyos resultados fueron normales, a excepción del paciente con discrepancia del grupo sanguíneo que presento un cariotipo de 46XY t (9;22) lo que estaría acorde con los reportes de otros estudios sobre la discrepancias sérico-globulares, donde se menciona que la pérdida de expresión de antígenos del grupo sanguíneo son causadas por alteraciones genéticas como translocaciones, delecciones, mutaciones y metilaciones del ADN que afecten el gen del grupo sanguíneo ABO localizado en el cromosoma 9.
In the present study we determined the incidence of discrepancies globular serum-blood in patients group "A" with de novo acute myeloid leukemia Hematology Service of the National Hospital Edgardo Rebagliati Matins during 2011. There were a total of 20 patients diagnosed with acute myeloid leukemia which 13 were blood group "O", 01 were blood group "B" and 06 blood group "A". Blood group was confirmed in tube (serum-globular) to patients of blood group "A", of which five of them presented a reading of 4+ (four crosses) in the globular test and found no discrepancies with the test serum. Only one male patient presented a reading of 2+ (two crosses) in the globular test and serum test gave a reading of 4+. It also collected the reports of the karyotype of each patient, the results were normal, except for the patient with blood group discrepancy that showed a karyotype of 46XY t (9;22) which would be consistent with reports from other studies on the discrepancíes serum-globular, which mentions that the loss of expression of blood group antigens are caused by genetic alterations such as translocations, deletions, mutations and DNA methylation affecting the ABO blood group gene on chromosome 9.