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The cytokine signature present in COVID-19 could provide information on the pathogenic mechanisms of the disease and could identify possible prognostic biomarkers and possible therapeutic targets. In this longitudinal work, we studied the clinical and biochemical parameters and circulating cytokine levels of 146 patients at the time of admission for COVID-19 and 4–6 weeks later. The main objective of this study was to determine whether basal cytokines could be early prognostic biomarkers of COVID-19, and also to analyze the impact of comorbidities, such as obesity or metabolic syndrome (MS), in the cytokine profile. The levels of most inflammatory cytokines were elevated on admission in relation to the level that was reached 4–6 weeks later, except for IL-1β, which was lower on admission; these levels were irrespective of the presence of obesity or MS since the cytokine storm masks these inflammatory processes. Among the cytokines analyzed, those that correlated with a worse prognosis of COVID-19 were resistin, IL-6, IL-8, IL-15, MCP-1 and TNF-α. Specifically, resistin and IL-15 are the best early predictors of requiring invasive ventilation. Therefore, resistin and IL-15 should be included in the personalized treatment decision algorithm of patients with COVID-19.

Clinical benefits using the 23-valent pneumococcal polysaccharide vaccine (PPsV23) or the 13-valent pneumococcal conjugate vaccine (PCV13) in adults are controversial. This study investigated clinical effectiveness for both PPsV23 and PCV13 in preventing pneumonia among middle-aged and older adults.Population-based cohort study involving 2,025,730 persons ≥50 years in Catalonia, Spain, who were prospectively followed between 01/01/2015 and 31/12/2016. Primary outcomes were hospitalisation from pneumococcal or all-cause pneumonia and main explanatory variable was PCV13/PPsV23 vaccination status. Multivariable Cox regression models were used to estimate vaccination effectiveness adjusted for age and baseline-risk conditions.Cohort members were followed for 3,897,151 person-years (17,496 PCV13 vaccinated and 1,551,502 PPsV23 vaccinated), observing 3259 pneumococcal pneumonias (63 in PCV13 vaccinated, 2243 in PPsV23 vaccinated) and 24,079 all-cause pneumonias (566 in PCV13 vaccinated, 17,508 in PPsV23 vaccinated). Global incidence rates (per 100,000 person-years) were 83.6 for pneumococcal pneumonia (360.1 in PCV13 vaccinated, 144.6 in PPsV23 vaccinated) and 617.9 for all-cause pneumonia (3235.0 in PCV13 vaccinated, 1128.5 in PPsV23 vaccinated). In the multivariable analyses, the PCV13 appeared significantly associated with an increased risk of pneumococcal pneumonia (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.17-1.97; p = 0.002) and all-cause pneumonia (HR: 1.76; 95% CI: 1.61-1.92; p 0.001) whereas the PPsV23 did not alter the risk of pneumococcal pneumonia (HR: 1.08; 95% CI: 0.98-1.19; p = 0.132) and slightly increased the risk of all-cause pneumonia (HR: 1.17; 95% CI: 1.13-1.21; p 0.001). In stratified analyses focused on specific target population subgroups (i.e., elderly people, at-risk and high-risk individuals), protective effects of vaccination did not emerge either.Data does not support clinical benefits from pneumococcal vaccination (nor PCV13 neither PPsV23) against pneumonia among Catalonian adults in the current era of universal PCV's childhood immunisation.

Nuclear magnetic resonance (NMR)-based advanced lipoprotein tests have demonstrated that LDL and HDL particle numbers (LDL-P and HDL-P) are more powerful cardiovascular (CV) risk biomarkers than conventional cholesterol markers. Of interest, in people living with HIV (PLHIV), predictors of preclinical atherosclerosis and vascular dysfunction may be associated with impaired immune function. We previously stated that immunological non-responders (INR) were at higher CV risk than immunological responders (IR) before starting antiretroviral therapy (ART). Using Liposcale® tests, we characterized the lipoprotein profile from the same cohort of PLHIV at month 12 and month 36 after starting ART, intending to explore what happened with these indicators of CV risk during viral suppression. ART initiation dissipates the differences in lipoprotein-based CV risk markers between INR and IR, and only an increase in the number of HDL-P was found in INR + IR when compared to controls (p = 0.047). Interestingly, CD4+ T-cell counts negatively correlated with medium HDL-P concentrations at month 12 in all individuals (ρ = -0.335, p = 0.003). Longitudinal analyses showed an important increase in LDL-P and HDL-P at month 36 when compared to baseline values in both IR and INR. A proper balance between a proatherogenic and atherogenic environment may be related to the reconstitution of CD4+ T-cell count in PLHIV., This research was funded by the Fondo de Investigacion Sanitaria [PI16/00503, PI19/01337 and PI20/00326]-ISCIII-FEDER (co-funded by the European Regional Development Fund/European Social Fund; “A way to make Europe”/”Investing in your future”); Programa de Suport als Grups de Recerca AGAUR (2017SGR948), the SPANISH AIDS Research Network [RD16/0025/0006]-ISCIII-FEDER (Spain) and the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas-ISCIII (CIBERINFEC) [CB21/13/00020], Madrid, Spain. JM is supported by the Universitat Rovira I Virgili under grant agreement “2019PMF-PIPF-18”, through the call “Martí Franquès Research Fellowship Programme”. FV is supported by grants from the Programa de Intensificación de Investigadores (INT20/00031)-ISCIII and by “Premi a la Trajectòria Investigadora dels Hospitals de l’ICS 2018”. AR is supported by a grant from IISPV through the project “2019/IISPV/05” (Boosting Young Talent), by GeSIDA through the “III Premio para Jóvenes Investigadores 2019” and by the Instituto de Salud Carlos III (ISCIII) under grant agreement “CP19/00146” through the Miguel Servet Program.

Introducción: Para hacer frente a la pandemia actual causada por el nuevo coronavirus SARS-CoV-2 se han desarrollado recientemente varios inmunoensayos serológicos con el objetivo de ser utilizados como herramienta diagnóstica complementaria y apoyar la técnica de RT-PCR actualmente considerada como el "estándar de oro". Sin embargo, estos nuevos ensayos deben evaluarse y validarse. El objetivo de este estudio fue evaluar cinco inmunoensayos (dos ELISA y tres ensayos CLIA) y una prueba inmunocromatográfica rápida para la detección de anticuerpos anti-SARS-CoV-2. Métodos: Se utilizaron cinco inmunoensayos semicuantitativos (MENARINI®, PALEX®, VIRCLIA®, ROCHE® y SIEMENS®) y un test de inmunocromatografía rápida (WONDFO®). Se estudiaron un total de 124 muestras. Las muestras de suero (n = 78) se obtuvieron de pacientes COVID-19 confirmados por RT-PCR en tiempo real / criterios epidemiológicos-clínico-radiológicos. Las muestras control negativas (n = 46) pertenecieron a personal sanitario involucrado en un estudio de seroprevalencia. Resultados: En general, las pruebas mostraron sensibilidades en torno al 70-90% y especificidades superiores al 95%, incluso la prueba inmunocromatográfica. Además, observamos muy buenas concordancias entre ellas, presentando mayores sensibilidades para la detección de anticuerpos IgG que para IgM (índice kappa de Cohen de 0,95 para VIRCLIA® IgG con ROCHE®), así como un buen poder diagnóstico de las técnicas determinado por las curvas ROC. Conclusiones: Este estudio demuestra el buen rendimiento de los diferentes inmunoensayos para ser empleados en la práctica clínica como apoyo en el proceso de diagnóstico, en el desarrollo de vacunas y estudios seroepidemiológicos de COVID-19.

Resumen Objetivo Describir las caracteristicas clinicas y respiratorias de una cohorte de 43 pacientes con COVID-19 tras 28 dias de evolucion. Diseno Prospectivo, observacional en un solo centro. Ambito Medicina intensiva. Pacientes Pacientes ingresados por COVID-19 e insuficiencia respiratoria. Intervenciones Ninguna. Variables Se obtuvieron de forma automatica variables demograficas, de gravedad, de laboratorio, de asistencia ventilatoria recibida (oxigenoterapia alto flujo [OAF] y ventilacion mecanica invasiva [VMI]), de oxigenacion (PaO2, PaO2/FiO2) y de complicaciones. Los pacientes se dividieron en 3 grupos: supervivientes (G1), fallecidos (G2) y aquellos que continuaban ingresados (G3). Se utilizo la prueba de Chi-cuadrado o de Fisher (variables categoricas) y la U de Mann-Whitney o Wilcoxon para analizar la diferencia entre medianas. Se considero significativo un valor de p Resultados Se incluyeron 43 pacientes (G1 = 28 [65,1%]; G2 = 10 [23,3%] y G3 = 5 [11,6%]), edad 65 (52-72) anos, 62% varones, APACHE II 18 (15-24), SOFA 6 (4-7), hipertension arterial (30,2%) y obesidad (25,6%) fueron las comorbilidades mas frecuentes. La OAF fue usada en el 62,7% de pacientes, el 85% fracaso. El 95% de los pacientes necesito VMI y el 85% ventilacion en prono. En la poblacion general, la PaO2/FiO2 inicial mejoro a los 7 dias (165 [125-210] vs. 194 [153-285]; p = 0,02), al igual que en el G1 (164 [125-197] vs. 207 [160-294]; p = 0,07), pero no en el G2 (163 [95-197] vs. 135 [85-177]). No se observo co-infeccion bacteriana. El desarrollo de neumonia asociada a la VMI fue elevado (13 episodios/1.000 dias de VMI). Conclusiones Los pacientes con COVID-19 requieren VMI precoz, elevada frecuencia de ventilacion en prono y presentan alta prevalencia de fracaso a la OAF. La falta de mejoria de la PaO2/FiO2 a los 7 dias podria ser un marcador de pronostico.

Population-based data on the current Covid-19 pandemic is scarce. This study investigated incidence and risk to suffer Covid-19 by baseline underlying conditions in people ≥50 years in Tarragona region across march-april 2020.Population-based retrospective cohort study involving 79,071 adults ≥50 years-old in Tarragona region (Southern Catalonia, Spain). Cohort characteristics (age, sex, residence, vaccinations history and comorbidities) were established at baseline, and Covid-19 cases occurring between 01/03/2020-30/04/2020 were registered. Cox regression analysis calculating Hazard ratios (HRs) adjusted by age, sex and comorbidities was used to estimate risk for Covid-19.Across study period, 1,547 cohort members were PCR tested (22.6% positive) and 367 were presumptive cases without PCR tested. Considering PCR-confirmed Covid-19, incidence (per 100,000 persons-period) was 441 overall (248, 141, 424, 1,303 and 3,135 in 50-59, 60-69, 70-79, 80-89 and ≥90 years-old, respectively; 380 in men and 497 in women; 259 in community-dwelling and 10,571 in nursing-home). By comorbidities, maximum incidence emerged among persons with neurological disease (2,723), atrial fibrillation (1,348), chronic renal failure (1,050), cardiac disease (856), respiratory disease (798) and diabetes (706). Lower incidence appeared in rheumatic diseases (230) and smokers (180). In multivariable analysis focused on community-dwelling individuals (N=77,671), only cardiac disease (HR: 1.47; 95% CI: 1.01-2.15; p=0.045) and respiratory disease (HR: 1.75; 95% CI: 1.00-3.02; p=0.051) were associated with an increased risk, whereas smoking (HR:0.43; 95% CI: 0.25-0.74; p=0.002) and influenza vaccinated (HR: 0.63; 95% CI: 0.43-0.92; p=0.015) appeared associated with a decreased risk.Apart of increasing age and nursing-home residence, chronic respiratory and cardiac disease appear at increased risk for suffering covid19. This study investigated population-based incidence of Covid-19 infection by underlying conditions among adults ≥50 years in Tarragona (Southern Catalonia, Spain) across two first months pandemic period.Los datos clínico-epidemiológicos de base poblacional durante la actual pandemia de Covid-19 son escasos. Este estudio investigó la incidencia y riesgo de sufrir Covid-19 según condiciones basales subyacentes en la población ≥50 años de Tarragona durante marzo-abril 2020.Estudio de cohortes retrospectivo que incluyó a 79.071 personas ≥50 años en el área de Tarragona. Se establecieron características basales de la cohorte (edad, sexo, residencia, vacunaciones y comorbilidades previas), y se registró la ocurrencia de Covid-19 entre 01/03/2020-30/04/2020. Para la estimación de riesgos se realizó regresión de Cox, con cálculo de Hazard ratios (HRs) ajustados por edad, sexo y comorbilidad.Se realizaron PCR-tests en 1.547 personas (22,6% positivos) y 367 fueron codificados como presuntos casos sin realizarse PCR-test. Considerando Covid-19 confirmada (PCR positivo), la incidencia (por 100.000 personas-periodo) fue de 441 (248, 141, 424, 1.303 y 3.135 en 50-59, 60-69, 70-79, 80-89 y ≥90 años, respectivamente; 380 en hombres frente a 497 en mujeres; 259 residentes en la comunidad respecto a 10.571 en institucionalizados). Según comorbilidades, las máximas incidencias aparecieron en enfermedad neurológica (2.723), fibrilación auricular (1.348), insuficiencia renal crónica (1.050), cardiopatía (856), enfermedad respiratoria (798) y diabetes (706). Menores incidencias aparecieron en enfermedad reumatológica (230) y fumadores (180). En personas no institucionalizadas (N=77.671), solo la enfermedad cardiaca (HR: 1,47; IC95%: 1,01-2,15; p=0,045) y respiratoria (HR: 1,75; IC95%: 1,00-3,02; p=0,051) se asociaron con incremento del riesgo, mientras que ser fumador (HR: 0,43; IC95%: 0,25-0,74; p=0,002) y vacunación antigripal en otoño previo (HR: 0,63; IC95%: 0,43-0,92; p=0,015) se asociaron con menor riesgo.Aparte de la edad y la institucionalización, la existencia de enfermedad respiratoria y/o cardiaca crónicas se asocia con una mayor incidencia de Covid-19 en adultos.

BACKGROUND We studied the impact of 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of invasive pneumococcal disease (IPD) and serotype distribution in a region with intermediate levels of vaccination (around 64% in children aged

Carbapenemase-producing (CP) Pseudomonas aeruginosa is rare compared with mutation-driven carbapenem-resistance, but this situation may be changing. A collection of CP P. aeruginosa isolates was characterized in this study. In 2016, 232 unduplicated carbapenem-resistant P. aeruginosa isolates, of which 71 (30.6%) carried carbapenemase genes, were submitted to the Spanish antibiotic reference laboratory and were further analysed by whole-genome sequencing (WGS). Of the 71 CP P. aeruginosa, 39 (54.9%) carried bla

Carbapenemase-producing (CP) Pseudomonas aeruginosa is rare compared with mutation-driven carbapenem-resistance, but this situation may be changing. A collection of CP P. aeruginosa isolates was characterized in this study. In 2016, 232 unduplicated carbapenem-resistant P. aeruginosa isolates, of which 71 (30.6%) carried carbapenemase genes, were submitted to the Spanish antibiotic reference laboratory and were further analysed by whole-genome sequencing (WGS). Of the 71 CP P. aeruginosa, 39 (54.9%) carried blaVIM-2, 14 (19.7%) blaVIM-1, 8 (11.3%) blaIMP-8, 6 (8.5%) blaVIM-20, 2 (2.8%) blaVIM-2 plus blaKPC-2, one (1.4%) blaIMP-13 and one (1.4%) blaVIM-1 plus blaIMP-18. Four sequence types (ST175, ST244, ST815 and ST155) encompassed 83.1% of the 71 CP P. aeruginosa; ST175 was detected in hospitals from seven provinces. Using core genome multilocus sequence typing (cgMLST), four clusters were detected: Cluster 1 included nine ST815/VIM-2 isolates; Cluster 2 included five ST175/VIM-2 isolates; Cluster 3 included seven ST244 isolates (five VIM-2 and two VIM-2 plus KPC-2); and Cluster 4 included 11 ST175 isolates (seven VIM-2 and four IMP-8). The average number of acquired resistance genes was significantly higher in the blaVIM-1-carying isolates (7.1 ± 0.94) than in the blaVIM-2-carrying isolates (4.5 ± 0.20). CP P. aeruginosa isolates are spreading in Spain, mainly due to the dissemination of high-risk clones such as ST175 and ST244 producing VIM and IMP carbapenemases. Emergence of CP P. aeruginosa is a cause of clinical and epidemiological concern.

The emergence of linezolid-resistant Enterococcus spp. (LRE) due to transferable resistance determinants is a matter of concern. To understand the contribution of the plasmid-encoded optrA and poxtA genes to the emergence of LRE, clinical isolates from different Spanish hospitals submitted to the Spanish Reference Laboratory from 2015-2018 were analysed. Linezolid resistance mechanisms were screened in all isolates by PCR and sequencing. Genetic relatedness of Enterococcus spp. carrying optrA and poxtA was studied by PFGE and MLST. Antimicrobial susceptibility was tested by broth microdilution using EUCAST standards. A total of 97 LRE isolates were studied, in 94 (96.9%) of which at least one resistance determinant was detected; 84/97 isolates (86.6%) presented a single resistance mechanism as follows: 45/84 (53.6%) carried the optrA gene, 38/84 (45.2%) carried the G2576T mutation and 1/84 (1.2%) carried the poxtA gene. In addition, 5/97 isolates (5.2%) carried both optrA and the G2576T mutation and 5/97 (5.2%) carried both optrA and poxtA. The optrA gene was more frequent in Enterococcus faecalis (83.6%) than Enterococcus faecium (11.1%) and was mainly associated with community-acquired urinary tract infections. Carriage of the poxtA gene was more frequent in E. faecium (13.9%) than E. faecalis (1.6%). Among the optrA-positive E. faecalis isolates, two main clusters were detected by PFGE. These two clusters belonged to ST585 and ST480 and were distributed throughout 11 and 6 Spanish provinces, respectively. This is the first description of LRE carrying the poxtA gene in Spain, including the co-existence of optrA and poxtA in five isolates.

Nowadays, after licensure of the second generation new pneumococcal conjugate vaccines (PCV10/PCV13). The epidemiology of the pneumococcal disease must be re-evaluated. The present study described incidence, lethality and serotype distribution of invasive pneumococcal disease (IPD) in the general population of Tarragona's region (Spain) after licensure of these vaccines.Retrospective study that included all cases of IPD (pneumococcus isolated in sterile sites) diagnosed among all-age individuals in the Spanish region of Tarragona (Tarragonés, Alt Camp and Baix Penedés counties) from 01/01/2012 to 31/12/2015. Incidence and lethality rates were estimated by age strata and globally. Similarly, it was determined the prevalence of IPD cases caused by serotypes included in the distinct formulations of multivalent conjugate vaccines (pcv7), PCV10 and PCV13) or 23-valent polysaccharide vaccine (PPV23).A total of 171 IPD cases were observed, which means a global incidence (per 100,000 persons-year) of 10.82 (7.86 in ≤14 years, 5.94 in 15-64 years and 36.46 in ≥65 years; p0.001). Overall lethality rate was 6.8% (none in children, 9,3% in people 15-64 years and 6.9% in people ≥65 years). A serotype was identified in 132 (77.2%) of the 171 studied samples. Serotype-vaccine coverages (cases due to vaccine-type serotypes) were 14.4%, 26.5%, 42.4% and 78.8% for the PCV7, PCV10, PCV13 and PPV23, respectively (p0.001).Incidence and lethality of IPD were intermediate-low in the region of Tarragona throughout 2012-2015. During this period, Serotype- vaccine coverage was almost double for the 23-valent than for the 13-valent vaccine.En la actualidad, tras la comercialización de las nuevas vacunas neumocócicas conjugadas de segunda generación (VNC10/VNC13), la epidemiología de la enfermedad neumocócica debe ser reevaluada. El presente estudio tuvo como objetivo describir la incidencia, letalidad y distribución serotípica de la enfermedad neumocócica invasiva (ENI) en la población general del área de Tarragona durante el cuatrienio posterior a la introducción de estas vacunas.Estudio observacional retrospectivo que incluyó todos los casos de ENI (Streptococcus pneumoniae aislado en sangre, líquido cefalorraquídeo, líquido pleural/articular/peritoneal o muestras de tejidos profundos obtenidas de forma estéril mediante punción-aspiración o biopsia) diagnosticados en el área de Tarragona (comarcas del Tarragonés, Alt Camp y Baix Penedés) entre 01/01/2012 y 31/12/2015. Se estimaron tasas de incidencia y letalidad (globalmente y por estratos etarios) y se determinó la prevalencia de casos causados por serotipos incluidos en las distintas formulaciones de vacunas antineumocócicas conjugadas heptavalente (VNC7), decavalente (VNC10), tridecavalente (VNC13) y polisacárida tricosavalente (VNP23).Se observaron 171 casos de ENI, lo que representó una incidencia (por 100.000 personas-año) de 10,82 (7,86 en ≤14 años, 5,94 en 15-64 años y 36,46 en ≥65 años; p0,001). La letalidad fue del 6,8% (ninguna en niños, 9,3% en 15-64 años y 6,9% en personas ≥65 años; p0,001). El serotipo responsable fue identificado en 132 (77,2%) de las 171 muestras estudiadas. La cobertura serotípica (casos causados por serotipos vacunales) fue del 14,4%, 26,5%, 42,4% y 78,8% para la VNC7, VNC10, VNC13 y VNP23, respectivamente (p0,001).Durante el periodo 2012-2015 la incidencia y letalidad por ENI fue intermedia-baja en el área de Tarragona, destacando que la cobertura serotípica fue casi doble para la vacuna 23-valente que para la 13-valente.

Pneumococcal infections remain a major health problem worldwide. This study analysed the distribution of distinct Streptococcus pneumoniae serotypes causing invasive pneumococcal disease (IPD) among all-age population in the region of Tarragona (Spain) throughout 2006-2009.An amount of 237 strains were evaluated, of which 203 (85.7%) were isolated from blood cultures, 14 (5.9%) from pleural fluids, 13 (5.5%) from CSF samples and 7 (3%) from other sterile sites. Forty-seven cases (19.8%) were children ≤ 14 years, 94 (39.7%) were patients 15-64 years and 96 (40.5%) were patients ≥ 65 years.Seven serotypes (1, 3, 6A, 7F, 12F, 14 and 19A) caused almost two thirds (63.3%) of cases among all-age patients. Serotype 1 was the most common serotype among children (44.7%) and among people 15-64 years (21.3%), whereas serotype 19A was the most common among people ≥ 65 years (12.5%).Among all-age population, serotype-vaccine coverage for the distinct pneumococcal polysaccharide vaccine (PPV) and conjugate vaccines (PCVs) were 17.3% for the PCV7, 49.8% for the PCV10, 73% for the PCV13 and 80.2% for the PPV23 (p0.001). Among children, vaccine-serotype coverage was 23.4% for the PCV7, 72.3% for the PCV10 and 83% for the PCV13. Among people ≥ 65 years, vaccine-serotype coverage was 62.5% for the PCV13 and 68.8% for the PPV23.A considerable proportion of IPD cases among our population would not be covered by the current pneumococcal vaccines.

An 8-year-old child originally from Morocco spent 1 month in Spain before complaining of abdominal pain for the previous 24 hours. There was no fever, vomiting, or diarrhea. He had lived in a rural area with dogs and sheep. Physical examination detected a mass in upper-right abdominal area. Chest X-ray showed right hemidiaphragmatic elevation. Ultrasonography showed a hypoechoic cyst mass of 12.5 × 10.5 × 8.5 cm without septum or calcifications that was a type CE1 according to the World Health Organization standardized classification.1,2 Computed tomography (Figure 1) and magnetic resonance imaging confirmed the diagnosis of hepatic hydatid cyst. Invasion into the biliary tree bile ducts, portal vein, or hepatic vein was not seen. IgE-specific serology for Echinococcus granulosus was positive (18.3 kUI/L). Serology for Entamoeba histolytica was negative. Aspartate and alanine amino transferase levels were increased (145 U/L and 151 U/L, respectively). Treatment with albendazole was initiated, and cystectomy was performed on the 18th day after admission. Gross examination showed hydatid sand; the protoscolex of E. granulosus was seen by light microscopy (Figure 2). Albendazole was maintained for 3 months and discontinued when ultrasound and serology confirmed resolution. The patient remained asymptomatic on follow-up visits. Figure 1. Image from a computed tomography study of the abdomen of the patient. Figure 2. Hydatid sand containing a protoscolex of Echinococcus granulosus was seen by light microcopy. This figure appears in color at www.ajtmh.org.