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BACKGROUND AND OBJECTIVE: Our study aims to compare the clinical and epidemiological characteristics, length of stay in the ICU, and mortality rates of COVID-19 patients admitted to the ICU who are fully vaccinated, partially vaccinated, or unvaccinated. PATIENTS AND METHODS: Retrospective cohort study (March 2020-March 2022). Patients were classified into unvaccinated, fully vaccinated, and partially vaccinated groups. We initially performed a descriptive analysis of the sample, a multivariable survival analysis adjusting for a Cox regression model, and a 90-day survival analysis using the Kaplan-Meier method for the death time variable. RESULTS: A total of 894 patients were analyzed: 179 with full vaccination, 32 with incomplete vaccination, and 683 were unvaccinated. Vaccinated patients had a lower incidence (10% vs. 21% and 18%) of severe ARDS. The survival curve did not show any differences in the probability of surviving for 90 days among the studied groups (p = 0.898). In the Cox regression analysis, only the need for mechanical ventilation during admission and the value of LDH (per unit of measurement) in the first 24 hours of admission were significantly associated with mortality at 90 days (HR: 5.78; 95% CI: 1.36-24.48); p = 0.01 and HR: 1.01; 95% CI: 1.00-1.02; p = 0.03, respectively. CONCLUSIONS: Patients with severe SARS-CoV-2 disease who are vaccinated against COVID-19 have a lower incidence of severe ARDS and mechanical ventilation than unvaccinated patients.
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Antecedentes y objetivo: Planteamos nuestro trabajo con el objetivo de comparar las características clínico epidemiológicas, la estancia en la UCI y la mortalidad de pacientes con COVID-19 que ingresaron en la UCI con vacunación completa, incompleta o sin vacunar. Pacientes y métodos: Estudio retrospectivo de cohortes (Marzo 2020-Marzo 2022). Los pacientes fueron clasificados en pacientes no vacunados, pauta de vacunación completa y pauta de vacunación incompleta. Se realizó inicialmente un análisis descriptivo de la muestra, un análisis multivariable de la supervivencia ajustando un modelo de regresión de Cox y un análisis de supervivencia a 90 días con el método de Kaplan-Meier para la variable de tiempo de muerte. Resultados: Fueron analizados los 894 pacientes: 179 con una pauta de vacunación completa, 32 con una pauta incompleta y 683 no estaban vacunados. Los enfermos vacunados presentaron con menor frecuencia (10% frente al 21% y 18%) un SDRA grave. La curva de supervivencia, no presentó diferencias en la probabilidad de sobrevivir a los 90 días entre los grupos estudiados (p=0,898). En el análisis de regresión de COX, únicamente la necesidad de VM durante el ingreso y el valor de LDH (por unidad de medida) en las primeras 24 horas de ingreso se asociaron de forma significativa con la mortalidad a los 90 días (HR: 5,78;IC95%: 1,36-24,48);p=0,01 y HR: 1,01;IC95%: 1,00-1,02;p=0,03 respectivamente. Conclusiones: Los pacientes vacunados frente al COVID-19 con enfermedad grave por SARS-CoV-2 presentan unas tasas de SDRA grave y de VM menores que las de aquellos pacientes no vacunados
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Introducción: las cánulas nasales de alto flujo de oxígeno en pacientes con insuficiencia respiratoria secundaria a neumonía por SARS-CoV-2 no han sido estudiadas desde un punto de vista coste-efectividad. Métodos: Análisis retrospectivo de datos obtenidos de enfermos ingresados en área-COVID de un servicio de medicina intensiva en un hospital de referencia de tercer nivel, entre marzo-diciembre de 2020. Se efectuó un análisis de coste efectividad en el que se comparan dos decisiones terapéuticas: la estrategia experimental se definió como una estrategia mixta consistente en la aplicación inicial de HFNO y aplicación de VNI sólo a los fracasos del HFNO. El objetivo del estudio fue establecer cuál de las dos alternativas se presentaba como la decisión racional óptima y la de mejor eficiencia económica (Razón de Coste-Efectividad Incremental por años de vida ganados). Resultados: En el análisis de coste-efectividad, comparando ambas estrategias terapéuticas, la probabilidad de que fuese más efectiva la estrategia experimental fue de 0,974, alcanzando la significación estadística: Diferencia de proporciones media = -0,113;IC 95% = -0,018 a -0,208. Ello corresponde a un NNT de 9 pacientes. La decisión óptima fue la estrategia de HFNO seguida de VMI en los fracasos del HFNO. Esta opción tuvo un RCEI de 5.582 euros por año de vida ganado. Conclusiones: Resulta importante establecer en el futuro marcadores fiables en el empleo del HFNO para que dicha terapia mejore sus prestaciones coste-efectivas.
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Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
Subject(s)
COVID-19 , Humans , COVID-19/genetics , SARS-CoV-2/genetics , Genome-Wide Association Study , Haplotypes , Polymorphism, GeneticABSTRACT
Objectives: The strain the SARS-COV-2 pandemic is putting on hospitals requires that predictive values are identified for a rapid triage and management of patients at a higher risk of developing severe COVID-19. We developed and validated a prognostic model of COVID-19 severity. Methods: A descriptive, comparative study of patients with positive vs. negative PCR-RT for SARS-COV-2 and of patients who developed moderate vs. severe COVID-19 was conducted. The model was built based on analytical and demographic data and comorbidities of patients seen in an Emergency Department with symptoms consistent with COVID-19. A logistic regression model was designed from data of the COVID-19-positive cohort. Results: The sample was composed of 410 COVID-positive patients (303 with moderate disease and 107 with severe disease) and 81 COVID-negative patients. The predictive variables identified included lactate dehydrogenase, C-reactive protein, total proteins, urea, and platelets. Internal calibration showed an area under the ROC curve (AUC) of 0.88 (CI 95%: 0.85-0.92), with a rate of correct classifications of 85.2% for a cut-off value of 0.5. External validation (100 patients) yielded an AUC of 0.79 (95% CI: 0.71-0.89), with a rate of correct classifications of 73%. Conclusions: The predictive model identifies patients at a higher risk of developing severe COVID-19 at Emergency Department, with a first blood test and common parameters used in a clinical laboratory. This model may be a valuable tool for clinical planning and decision-making.
ABSTRACT
Acute lung injury (ALI) is a critical inflammatory syndrome, characterized by increased diffuse inflammation and severe lung damage, which represents a clinical concern due to the high morbidity and mortality in critical patients. In last years, there has been a need to develop more effective treatments for ALI, and targeted drug delivery to inflamed lungs has become an attractive research field. Here, we present a nanodevice based on mesoporous silica nanoparticles loaded with dexamethasone (a glucocorticoid extensively used for ALI treatment) and capped with a peptide that targets the TNFR1 receptor expressed in pro-inflammatory macrophages (TNFR-Dex-MSNs) and avoids cargo leakage. TNFR-Dex-MSNs nanoparticles are preferentially internalized by pro-inflammatory macrophages, which overexpressed the TNFR1 receptor, with the subsequent cargo release upon the enzymatic hydrolysis of the capping peptide in lysosomes. Moreover, TNFR-Dex-MSNs are able to reduce the levels of TNF-α and IL-1ß cytokines in activated pro-inflammatory M1 macrophages. The anti-inflammatory effect of TNFR-Dex-MSNs is also tested in an in vivo ALI mice model. The administered nanodevice (intravenously by tail vein injection) accumulated in the injured lungs and the controlled dexamethasone release reduces markedly the inflammatory response (TNF-α IL-6 and IL-1ß levels). The attenuation in lung damage, after treatment with TNFR-Dex-MSNs, is also confirmed by histopathological studies. Besides, the targeted-lung dexamethasone delivery results in a decrease of dexamethasone derived side-effects, suggesting that targeted nanoparticles can be used for therapy in ALI and could help to overcome the clinical limitations of current treatments.
Subject(s)
Acute Lung Injury , Nanoparticles , Acute Lung Injury/drug therapy , Animals , Dexamethasone , Humans , Lung , Mice , Silicon DioxideABSTRACT
OBJECTIVE: Test whether high dose corticosteroid pulse therapy (HDCPT) with either methylprednisolone or dexamethasone is associated with increased survival in COVID-19 patients at risk of hyper-inflammatory response. Provide some initial diagnostic criteria using laboratory markers to stratify these patients. METHODS: This is a prospective observational study, 318 met the inclusion criteria. 64 patients (20.1%) were treated with HDCPT by using at least 1.5mg/kg/24h of methylprednisolone or dexamethasone equivalent. A multivariate Cox regression (controlling for co-morbidities and other therapies) was carried out to determine whether HDCPT (among other interventions) was associated with decreased mortality. We also carried out a 30-day time course analysis of laboratory markers between survivors and non-survivors, to identify potential markers for patient stratification. RESULTS: HDCPT showed a statistically significant decrease in mortality (HR = 0.087 [95% CI 0.021-0.36]; P < 0.001). 30-day time course analysis of laboratory marker tests showed marked differences in pro-inflammatory markers between survivors and non-survivors. As diagnostic criteria to define the patients at risk of developing a COVID-19 hyper-inflammatory response, we propose the following parameters (IL-6 > = 40 pg/ml, and/or two of the following: C-reactive protein > = 100 mg/L, D-dimer > = 1000 ng/ml, ferritin > = 500 ng/ml and lactate dehydrogenase > = 300 U/L). CONCLUSIONS: HDCPT can be an effective intervention to increase COVID-19 survival rates in patients at risk of developing a COVID-19 hyper-inflammatory response, laboratory marker tests can be used to stratify these patients who should be given HDCPT. This study is not a randomized clinical trial (RCT). Future RCTs should be carried out to confirm the efficacy of HDCPT to increase the survival rates of COVID-19.
Subject(s)
Adrenal Cortex Hormones/administration & dosage , COVID-19 Drug Treatment , Cytokine Release Syndrome/drug therapy , Adult , Aged , COVID-19/immunology , COVID-19/mortality , Cytokine Release Syndrome/immunology , Dexamethasone/pharmacology , Female , Hospitalization , Humans , Inflammation/immunology , Inflammation/prevention & control , Male , Methylprednisolone/pharmacology , Middle Aged , Prospective Studies , SARS-CoV-2/isolation & purification , Spain/epidemiology , Survival RateSubject(s)
Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Diffuse Axonal Injury/virology , Pneumonia, Viral/diagnosis , Adult , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Coronavirus Infections/complications , Diffuse Axonal Injury/diagnosis , Female , Humans , Pandemics , Pneumonia, Viral/complications , SARS-CoV-2ABSTRACT
BACKGROUND: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. METHODS: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case-control panels. RESULTS: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10-8) in the meta-analysis of the two case-control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P = 1.15×10-10; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P = 4.95×10-8, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group-specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P = 1.48×10-4) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P = 1.06×10-5). CONCLUSIONS: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.).