Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain. Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis. Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins. Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2020117979RB-I00Instituto de Salud Carlos III European Commission European Commission IMP/00019Junta de Andalucia COVID-0012-2020 PS-2020-342European Social Fund (ESF) 871075Carlos Loucera PAIDI2020-DOC_0035

Etiology and susceptbility to antimicrobials of urinary tract infections in patients of Rehabilitation Unit of a regional hospital

Objetivos: Conocer los resultados del estudio microbiológico de las muestras de orina de pacientes de la Unidad de Rehabilitación de un hospital regional, incluyendo los datos locales de sensibilidad antibiótica. Material y métodos: Se analizó la base de datos del Laboratorio de Microbiología del Hospital Universitario Virgen de las Nieves con los estudios microbiológicos de las muestras de orinas realizados durante el año 2012. Se investigó la etiología y la sensibilidad a los antibióticos de los uropatógenos más frecuentes presentes en 143 muestras de orina obtenidas mediante sondaje o cateterismo. Los resultados del estudio de 9066 muestras de orina de micción media de sujetos estudiados en Atención Primaria fueron utilizados como grupo control. Resultados: El 50% de los pacientes neurológicos presentaron urocultivos positivos, frente al 23% de los controles. E. coli fue el microorganismo más frecuentemente aislado en el grupo de enfermos neurológicos, al igual que en los controles. En el estudio de resistencias E. coli presentó altas tasas de resistencia a ampicilina, cotrimoxazol, ciprofloxacino y amoxicilina con ácido clavulánico. Conclusiones: E. coli es el microorganismo más frecuentemente aislado en los dos grupos de pacientes estudiados. Las resistencias a los antibióticos de los microorganismos procedentes de los dos grupos tienen patrones diferentes, siendo globalmente menor a fosfomicina.Objectives: Knowing the results of microbiological tests of urine samples of patients from the Rehabilitation Unit of a regional hospital, including local data of antibiotic susceptibility. Material and methods: We analyzed the database of the Microbiology Laboratory of the Hospital Universitario Virgen de las Nieves with microbiological studies conducted urine samples during 2012. We investigated the etiology and antimicrobial susceptibility of uropathogens frequently present in 143 urine samples. The 9066 survey results voiding urine mean in Primary Care study subjects were used as controls. Results: The 50% of neurological patients had positive urine cultures, versus 23% of controls. E. coli was the most frequently isolated organism group neurological patients, as in the controls. Resistance studies in E. coli showed high rates of resistance to ampicillin, cotrimoxazole, ciprofloxacin and amoxicillin with clavulanic acid. Conclusions: E. coli is the most frequently isolated microorganism in both groups of patients studied. The antibiotic resistance of microorganisms from the two groups have different patterns, being globally less to fosfomycin

Gender differences in the plasma concentration of the GAS6-TAM system in COVID-19 patients

Resumen del trabajo presentado en el 4th European Congress on Thrombosis and Haemostasis, celebrado en Gante (Bélgica), los días 14 y 15 de octubre de 2021Background: SARS-CoV-2 induces an immune response with potentially harmful effects for the patient due to an uncontrolled release of inflammatory factors, specially at the capillary wall. The vitamin K-dependent plasma protein GAS6 and the TAM (TYRO3, AXL, and MERTK) receptors play a relevant role among restorative mechanisms that counterbalance pro-inflammatory responses at the endothelial interface. Aims: To study the influence of gender on the effects of SARS-CoV-2 infection in the GAS6/TAM system, as reflected by plasma concentration at patient admittance at the emergency ward. Methods: The plasma content of GAS6, AXL, and MERTK was analyzed in a first group of 132 patients, 68 females and 64 males consecutively admitted to the emergency ward during the first peak of COVID-19. A confirmatory group was studied from the second wave of contagions. An analysis of gender differences in relation to the GAS6/TAM concentrations in plasma was performed on this population. Results: In accordance with recently published GAS6 levels, significantly higher in the SARS-CoV-2 positive than in negative patients, increased progressively with the severity of the disease in SARS-CoV-2 positive individual irrespective of the gender of the patient. In contrast, while soluble AXL exhibited higher plasma concentration in deceased patients and no significant differences were observed in MERTK concentration, differential gender analysis suggest differences in soluble TAM receptors. While a COVID-19 related increase in sAXL was observed in men, this was not the case in women. Oppositely, MERTK differences due to COVID-19 infection were only significant in women. Summary/Conclusion: GAS6-TAM system of ligands and receptors is implicated in the immune response to SARS-CoV-2 in patients from both genders. Plasma GAS6 levels paralleled COVID-19 severity being an early marker of disease prognosis in both sexes. In contrast, soluble TAM receptors presented a gender-specific behavior. Sex-related differences in sAXL and sMERTK expression in COVID-19 patients could affect therapy efficacy deserving further investigation

Infección por virus pandémico (H1N1) 2009 en Andalucía

Desde que en abril de 2009 la Organización Mundial de la Salud (OMS) alertó de la existencia de casos de infección humana por un nuevo virus de la gripe AH1N1 de origen porcino, las autoridades sanitarias de Andalucía activaron un plan específico de actuación para dar respuesta a la crisis sanitaria. Las actividades de vigilancia desarrolladas permitieron disponer de información oportuna sobre las características clínicas, epidemiológicas y virológicas de la enfermedad. En los primeros días se pusieron en marcha planes de contingencia basados en la vigilancia epidemiológica y medidas de control de brotes mediante sistemas de alerta y respuesta rápida. Tras la declaración de fase 6 de alerta pandémica la vigilancia centinela de gripe y de casos graves fueron de utilidad para la planificación de servicios sanitarios, para reducir la transmisión e identificar y para proteger a los grupos de población más vulnerables. El comportamiento de la gripe pandémica en Andalucía ha sido similar al observado en el resto del mundo. La tasa de ataque fue parecida a la de una temporada de gripe estacional y el pico de máxima incidencia se alcanzó en la semana 46/2009. La mayoría de los casos fueron leves y afectó sobre todo a población joven. En los casos hospitalizados la media de edad fue de 32 años. Las patologías previas de base y factores de riesgo mas frecuentes presentes en los casos graves fueron enfermedades pulmonares, tabaquismo y obesidad mórbida (IMC>40). Un escenario de impacto de la onda pandémica en Andalucía, con una tasa de ataque esperada de entre el 2 y 5%, se preparó teniendo en cuenta lo observado durante la onda epidémica en los países del hemisferio sur. Las características de la epidemia en cuanto a su magnitud, gravedad y letalidad, se ajustaron a este escenario utilizado

Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain. Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis. Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins. Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.This work was supported by Spanish Ministry of Science and Innovation (grant PID2020- 117979RB-I00), the Instituto de Salud Carlos III (ISCIII), co-funded with European Regional Development Funds (ERDF) (grant IMP/00019), and has also been funded by Consejería de Salud y Familias, Junta de Andalucía (grants COVID-0012-2020 and PS-2020-342) and the postdoctoral contract of Carlos Loucera (PAIDI2020- DOC_00350), co-funded by the European Social Fund (FSE) 2014-2020. ELIXIR-CONVERGE—H2020 (871075).Peer reviewe

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

Association of candidate gene polymorphisms with chronic kidney disease : Results of a case-control analysis in the NEFRONA cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionization-time of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD