Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control

Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography-electrospray ionization-quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients). Long-term viral and immunological HIV-1 control was found to be strongly associated with elevated tricarboxylic acid (TCA) cycle function. Interestingly, of the nine metabolites identified in the TCA cycle, α-ketoglutaric acid (p = 0.004), a metabolite implicated in the activation of the mTOR complex, a modulator of HIV latency and regulator of several biological processes, was found to be a key metabolite in the persistent control. On the other hand, a lipidomics panel combining 45 lipid species showed an optimal percentage of separation and an ability to differentiate LTEC-extreme from LTEC-losing, revealing that an elevated lipidomics plasma profile could be a predictive factor for the reignition of viral replication in LTEC individuals.This work was supported by the Fondo de Investigación Sanitaria [PI13/0796, PI16/00503, PI16/0684, PI18/1532, PI19/00004, PI19/01127, PI19/01337 PI16/001769, PI19/00973, 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); Gilead Fellowship Program GLD14/293; The SPANISH AIDS Research Network [RD16/0002/0001, RD16/0002/0002, RD16/0025/0006, RD16/0025/0013, and RD16/0025/0020]-ISCIII-FEDER (Spain); and the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas-ISCIII [CB21/13/00015, CB21/13/00020, and CB21/13/00044], 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.” NR is a Miguel Servet researcher from the ISCIII [CPII19/00025]. EY is supported by the Instituto de Salud Carlos III (ISCIII) under grant agreement “FI20/0011800” through the program “Contratos Predoctorales de Formación en Investigación en Salud.” ER-M was supported by the Spanish National Research Council (CSIC). FV is supported by grants from the Programa de Intensificación de Investigadores (INT20/00031)-ISCIII and by “Premi a la Trajectòria Investigadora als Hospitals de l’ICS 2018.” AR is supported by 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.S

Prevalencia de serotipos causantes de enfermedad neumocócica invasiva en el área de Tarragona, 2006-2009: cobertura de serotipos para las distintas formulaciones de vacuna antineumocócica.

ntroducció: Les infeccions pneumocòcciques representen un important problema de salut. El present estudi va analitzar la distribució dels distints serotips de Streptococcus pneumoniae causants de malaltia pneumocòccica invasiva (MPI) en la regió de Tarragona durant 2006-2009. Mètodes: S’avaluaren 237 soques, de les quals 203 (85,7%) corresponien a hemocultius, 14 (5,9%) a líquid pleural, 13 (5,5%) a líquid cefaloraquídi i 7 (3%) a altres fluids/teixits. Quaranta set mostres (19,8%) pertanyien a nens de ≤14 anys, 94 (39,7%) a persones 15-64 anys i 96 (40,5%) a persones ≥65 anys. Resultats: Set serotips (1, 3, 6A, 7F, 12F, 14 i 19A) suposaren quasi dos terços (63,3%) del total de serotips identificats en pacients de qualsevol edat. El serotip 1 fou el més comú entre els nens (44,7%) i persones de 15-64 anys (21,3%), mentre que el serotip 19A fou el més comú entre les persones ≥65 anys (12,5%). Entre la població general, la cobertura de serotips per a les distintes vacunas antipneumocòcciques polisacàrida (VNP) i conjugades (VNC) fou del 17,3% per a la VNC7, del 49,8% per a la VNC10, del 73% per a la VNC13 i del 80,2% per a la VNP23 (p<0,001). Entre els nens, les cobertures serotípiques foren 23,4% per a la VNC7, del 72,3% per a la VNC10 i del 83% per a la VNC13. Entre les persones ≥65 anys, la cobertura serotípica fou del 62,5% per a la VNC13 i del 68,8% per a la VNP23. Conclusión: Una considerable proporció dels casos de MPI en la nostra població no estarien coberts per ninguna de les vacunas actuals.Introducción: Las infecciones neumocócicas representan un importante problema de salud. El presente estudio analizó la distribución de los distintos serotipos de Streptococcus pneumoniae causantes de enfermedad neumocócica invasiva (ENI) en la región de Tarragona durante 2006-2009. Métodos: Se evaluaron 237 cepas, de las cuales 203 (85,7%) correspondían a hemocultivos, 14 (5,9%) a líquido pleural, 13 (5,5%) a líquido cefalorraquídeo y 7 (3%) a otros fluidos/tejidos. Cuarenta y siete muestras (19,8%) pertenecían a niños de ≤14 años, 94 (39,7%) a personas 15-64 años y 96 (40,5%) a personas ≥65 años. Resultados: Siete serotipos (1, 3, 6A, 7F, 12F, 14 Y 19A) supusieron casi dos tercios (63,3%) del total de serotipos identificados en pacientes de cualquier edad. El serotipo 1 fue el más común entre los niños (44,7%) y personas de 15-64 años (21,3%), mientras que el serotipo 19A fue el más común entre las personas ≥65 años (12,5%). Entre la población general, la cobertura de serotipos para las distintas vacunas antineumocócicas polisacárida (VNP) y conjugadas (VNC) fue del 17,3% para la VNC7, del 49,8% para la VNC10, del 73% para la VNC13 y del 80,2% para la VNP23 (p<0,001). Entre los niños, las coberturas serotípicas fueron 23,4% para la VNC7, del 72,3% para la VNC10 y del 83% para la VNC13. Entre las personas ≥65 años, la cobertura serotípica fue del 62,5% para la VNC13 y del 68,8% para la VNP23. Conclusión: Una considerable proporción de los casos de ENI en nuestra población no estarían cubiertos por ninguna de las vacunas actuales.Background. Pneumococcal infections remain a major health problem worldwide. This study analysed the distribution of distinct Streptococcus pneumoniae serotypes causing inva¬sive pneumococcal disease (IPD) among all-age population in the region of Tarragona (Spain) throughout 2006-2009. Methods. 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. Results. Seven serotypes (1, 3, 6A, 7F, 12F, 14 and 19A) caused almost two thirds (63.3%) of cases among all-age pa¬tients. Serotype 1 was the most common serotype among chil¬dren (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 cover¬age 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 (p<0,001). 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. Conclusion. A considerable proportion of IPD cases among our population would not be covered by the current pneumococcal vaccine

Prognostic Value of Procalcitonin and C-Reactive Protein in 1608 Critically Ill Patients with Severe Influenza Pneumonia

Proteïna C-reactiva; Pneumònia; ProcalcitoninaProteína C-reactiva; Neumonía; ProcalcitoninaC-Reactive protein; Pneumonia; ProcalcitoninBackground: Procalcitonin (PCT) and C-Reactive protein (CRP) are well-established sepsis biomarkers. The association of baseline PCT levels and mortality in pneumonia remains unclear, and we still do not know whether biomarkers levels could be related to the causative microorganism (GPC, GNB). The objective of this study is to address these issues. Methods: a retrospective observational cohort study was conducted in 184 Spanish ICUs (2009–2018). Results: 1608 patients with severe influenza pneumonia with PCT and CRP available levels on admission were included, 1186 with primary viral pneumonia (PVP) and 422 with bacterial Co-infection (BC). Those with BC presented higher PCT levels (4.25 [0.6–19.5] versus 0.6 [0.2–2.3]ng/mL) and CRP (36.7 [20.23–118] versus 28.05 [13.3–109]mg/dL) as compared to PVP (p < 0.001). Deceased patients had higher PCT (ng/mL) when compared with survivors, in PVP (0.82 [0.3–2.8]) versus 0.53 [0.19–2.1], p = 0.001) and BC (6.9 [0.93–28.5] versus 3.8 [0.5–17.37], p = 0.039). However, no significant association with mortality was observed in the multivariate analysis. The PCT levels (ng/mL) were significantly higher in polymicrobial infection (8.4) and GPC (6.9) when compared with GNB (1.2) and Aspergillus (1.7). The AUC-ROC of PCT for GPC was 0.67 and 0.32 for GNB. The AUROC of CRP was 0.56 for GPC and 0.39 for GNB. Conclusions: a single PCT/CRP value at ICU admission was not associated with mortality in severe influenza pneumonia. None of the biomarkers have enough discriminatory power to be used for predicting the causative microorganism of the co-infection.This research received no external funding. This study was supported by the Spanish Intensive Care Society (SEMICYUC) and Ricardo Barri Casanovas Foundation (Alejandro Rodríguez). The study sponsors have no role in the study design, data collection, data analysis, data interpretation, or writing of the report

Epidemiología de la enfermedad neumocócica invasiva en la región de Tarragona, 2012-2015: incidencia, letalidad y cobertura de serotipos para las distintas formulaciones vacunales antineumocócicas

ABSTRACT Background: 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. Methods: 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). Results: 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; p<0.001). 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 (p<0.001). Conclusion: 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.RESUMEN Fundamentos: 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. Métodos: 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). Resultados: 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; p<0,001). La letalidad fue del 6,8% (ninguna en niños, 9,3% en 15-64 años y 6,9% en personas ≥65 años; p<0,001). 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 (p<0,001). Conclusiones: 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

Evaluación de la incidencia y perfil de riesgo de COVID-19 según comorbilidad previa en adultos ≥50 años del área de Tarragona

Background: 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. Methods: 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. Results: 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. Conclusions: Apart of increasing age and nursinghome 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.Fundamentos: 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. Métodos: 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. Resultados: 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. Conclusiones: 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

Lipoprotein Profile in Immunological Non-Responders PLHIV after Antiretroviral Therapy Initiation.

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