Vaccine breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota, and Omicron

Replication of SARS-CoV-2 in the human population is defined by distributions of mutants that are present at different frequencies within the infected host and can be detected by ultra-deep sequencing techniques. In this study, we examined the SARS-CoV-2 mutant spectra of amplicons from the spike-coding (S-coding) region of 5 nasopharyngeal isolates derived from patients with vaccine breakthrough. Interestingly, all patients became infected with the Alpha variant, but amino acid substitutions that correspond to the Delta Plus, Iota, and Omicron variants were present in the mutant spectra of the resident virus. Deep sequencing analysis of SARS-CoV-2 from patients with vaccine breakthrough revealed a rich reservoir of mutant types and may also identify tolerated substitutions that can be represented in epidemiologically dominant variants.This work was supported by the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 Research Call COV20/00181) and co-financed by the European Development Regional Fund “A way to achieve Europe.” The work was also supported by grants CSIC-COV19-014 from the CSIC, project 525/C/2021 from the Fundació La Marató de TV3; PID2020-113888RB-I00 from the Ministerio de Ciencia e Innovación; BFU2017-91384-EXP from the Ministerio de Ciencia, Innovación y Universidades (MCIU);PI18/00210 and PI21/00139 from the Instituto de Salud Carlos III; and S2018/BAA-4370 (PLATESA2) from the Comunidad de Madrid/ FEDER. This research work was also funded by the European Commission – NextGenerationEU (regulation EU 2020/2094), through the CSIC’s Global Health Platform (PTI Salud Global). CP and PM are supported by the Miguel Servet programme of the Instituto de Salud Carlos III (CPII19/00001 and CP16/00116, respectively), cofinanced by the European Regional Development Fund (ERDF). CIBERehd is funded by the Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). BMG is supported by predoctoral contract PFIS FI19/00119 from the Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo), cofinanced by the Fondo Social Europeo (FSE). CGC is supported by predoctoral contract PRE2018- 083422 from the MCIU. BS was supported by a predoctoral research fellowship (Doctorados Industriales, DI-17-09134) from the Spanish Ministry of Economy and Competitiveness (MINECO).Peer reviewe

Renal Function Impact in the Prognostic Value of Galectin-3 in Acute Heart Failure

[Abstract] Introduction: Galectin-3 (Gal-3) is an inflammatory marker associated with the development and progression of heart failure (HF). A close relationship between Gal-3 levels and renal function has been observed, but data on their interaction in patients with acute HF (AHF) are scarce. We aim to assess the prognostic relationship between renal function and Gal-3 during an AHF episode. Materials and methods: This is an observational, prospective, multicenter registry of patients hospitalized for AHF. Patients were divided into two groups according to estimated glomerular filtration rate (eGFR): preserved renal function (eGFR ≥ 60 mL/min/1.73 m2) and renal dysfunction (eGFR <60 mL/min/1.73 m2). Cox regression analysis was performed to evaluate the association between Gal-3 and 12-month mortality. Results: We included 1,201 patients in whom Gal-3 values were assessed at admission. The median value of Gal-3 in our population was 23.2 ng/mL (17.3-32.1). Gal-3 showed a negative correlation with eGFR (rho = -0.51; p < 0.001). Gal-3 concentrations were associated with higher mortality risk in the multivariate analysis after adjusting for eGFR and other prognostic variables [HR = 1.010 (95%-CI: 1.001-1.018); p = 0.038]. However, the prognostic value of Gal-3 was restricted to patients with renal dysfunction [HR = 1.010 (95%-CI: 1.001-1.019), p = 0.033] with optimal cutoff point of 31.5 ng/mL, with no prognostic value in the group with preserved renal function [HR = 0.990 (95%-CI: 0.964-1.017); p = 0.472]. Conclusions: Gal-3 is a marker of high mortality in patients with acute HF and renal dysfunction. Renal function influences the prognostic value of Gal-3 levels, which should be adjusted by eGFR for a correct interpretation.Grant No. RD06-0003-0000 Grant No. RD12/0042/000

Serum Potassium Dynamics During Acute Heart Failure Hospitalization

[Abstract] Background. Available information about prognostic implications of potassium levels alteration in the setting of acute heart failure (AHF) is scarce. Objectives. We aim to describe the prevalence of dyskalemia (hypo or hyperkalemia), its dynamic changes during AHF-hospitalization, and its long-term clinical impact after hospitalization. Methods. We analyzed 1779 patients hospitalized with AHF who were included in the REDINSCOR II registry. Patients were classified in three groups, according to potassium levels both on admission and discharge: hypokalemia (potassium  5 mEq/L). Results. The prevalence of hypokalemia and hyperkalemia on admission was 8.2 and 4.6%, respectively, and 6.4 and 2.7% at discharge. Hyperkalemia on admission was associated with higher in-hospital mortality (OR = 2.32 [95% CI: 1.04–5.21] p = 0.045). Among patients with hypokalemia on admission, 79% had normalized potassium levels at discharge. In the case of patients with hyperkalemia on admission, 89% normalized kalemia before discharge. In multivariate Cox regression, dyskalemia was associated with higher 12-month mortality, (HR = 1.48 [95% CI, 1.12–1.96], p = 0.005). Among all patterns of dyskalemia persistent hypokalemia (HR = 3.17 [95% CI: 1.71–5.88]; p < 0.001), and transient hyperkalemia (HR = 1.75 [95% CI: 1.07–2.86]; p = 0.023) were related to reduced 12-month survival. Conclusions. Potassium levels alterations are frequent and show a dynamic behavior during AHF admission. Hyperkalemia on admission is an independent predictor of higher in-hospital mortality. Furthermore, persistent hypokalemia and transient hyperkalemia on admission are independent predictors of 12-month mortality.This work is funded by the Instituto de Salud Carlos III (Ministry of Economy, Industry, and Competitiveness) and co-funded by the European Regional Development Fund, through the CIBER in cardiovascular diseases (CB16/11/00502)

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

The populist radical right and the public administration

In this chapter we are going to describe the possible implications that the rise of the extreme right or populist radical right2 may have on public administration. To do this, the “winning formula” (Forti 2021: 80 et seq.) of the extreme right is taken as a reference in the framework of a State reinforced in its central bodies against the meso-governments and the European Union. This winning formula, in the terms explained by Forti, incorporates xenophobia and a clearly authoritarian and conservative orientation at the level of values, along with a markedly neoliberal tone at the economic level. It is not unknown that the intensity with which these factors are presented in the far-right agenda depends on the country, the context and the tacticism, also confirming that in recent years there are family parties that are gradually moving towards a chauvinist welfare state. (Welfare Chauvinism), and even towards a certain centrism, more imposed than real, in economic and value terms. It should be recognized in advance that direct references to the Administration or public function by the populist radical right parties are scarce and almost always critical, which does not prevent significant conclusions from being drawn from the position they defend regarding the strengthening of state nationalism. and its position on public policies in a multilevel management framework, in which the European Union appears as a relevant actor. The impact of the agenda of this radical right on the Public Administration is analyzed in this chapter through the following sections: firstly, the analysis starts from recognizing how the position of the extreme right of strengthening the national level of government impacts the system. of intergovernmental relations of each country, and then, secondly, analyze its influence on public policies. Thirdly, the supranational dimension of national policies and the impact of the main proposals of said parties on the matter are put on the board. And finally, the findings of this analysis are synthetically related.En este capítulo vamos a describir las posibles implicaciones que el auge de la extrema derecha o derecha radical populista2 puede tener sobre la Administración pública. Para ello se toma como referencia la “fórmula ganadora” (Forti 2021: 80 y ss.) de la ultraderecha en el marco de un Estado reforzado en sus órganos centrales frente a los mesogobiernos y la Unión Europea. Dicha fórmula ganadora, en los términos explicitados por Forti incorpora la xenofobia y una orientación claramente autoritaria y conservadora en el plano de los valores, junto a un tono marcadamente neoliberal en el plano económico. No se desconoce que la intensidad con que se presentan estos factores en la agenda ultraderechista dependen del país, del contexto y del tacticismo, constatando además que en los últimos años hay partidos de la familia que van poco a poco transitando hacia un Estado de bienestar chovinista (Welfare Chauvinism), e incluso hacia un cierto centrismo, más impostado que real, en términos económicos y de valores. Cabe reconocer de antemano que las referencias directas a la Administración o función pública por parte de los partidos de derecha radical populista son escasas y casi siempre críticas, lo que no impide obtener conclusiones significativas a partir de la posición que defienden respecto al fortalecimiento del nacionalismo estatal y la posición de éste sobre las políticas públicas en un marco de gestión multinivel, en que aparece como actor relevante la Unión Europea. El impacto de la agenda de esa derecha radical sobre la Administración Pública se analiza en este capítulo mediante los siguientes epígrafes: en primer lugar, el análisis parte de reconocer cómo la posición de la extrema derecha de fortalecer el nivel nacional de gobierno impacta sobre el sistema de relaciones intergubernamentales de cada país, para posteriormente, en segundo lugar, analizar su influencia sobre las políticas públicas. En tercer término se pone sobre el tablero la dimensión supranacional de las políticas nacionales y el impacto de las principales propuestas de dichos partidos sobre el particular. Y finalmente se relacionan sintéticamente los hallazgos de este análisisUniversidad Complutense de MadridUniversidad de Evora (Portugal)Depto. de Ciencia Política y de la AdministraciónInstituto Complutense de Ciencia de la Administración (ICCA)TRUEpu

Civil servants in face of a multilevel governance context: crisis and reinvention

This chapter aims to analyze the Spanish public service before the important process of change that must be addressed in our days, derived in substantive part of multilevel governance in which the public affairs today. Faced with a liquid society, the responses of Public administration and functions cannot be traditional, or not only the traditional ones, but it is necessary to reflect on the Administration model Spanish, of which our state public function is contingent, in order to determine what are the challenges to be addressed and, within them, what is the profile of civil servant that must be promoted in the new multi-level management environment. The chapter begins with an approach to the essence of public service, framed in a concept of Administration rediscovered from the classics of Administration Science and that allows us to limit the perimeter conceptual of said public function (Section 1). Next, a evaluation of the complex environment in which public affairs move in the current situation (Section 2), with a view to establishing the dominant model of the Administration Spanish public in crisis and the future challenges it must face. Precisely, these challenges require a new profile and reinvention of the public function of the State, especially in a multi-level governance State complex as ours is (Section 4).En el presente capítulo se pretende analizar la función pública española ante el importante proceso de cambio que debe abordar en nuestros días, derivado enparte sustantiva de la gobernanza multinivel en que se mueven y concretan los asuntos públicos en la actualidad. Ante una sociedad líquida, las respuestas de la Administración y función públicas no pueden ser las tradicionales, o no solo las tradicionales, sino que se impone reflexionar sobre el modelo de Administración española, del cual es contingente nuestra función pública estatal, a fin de determinar cuáles son los desafíos a abordar y, dentro de ellos, cuál es el perfil de funcionario que debe impulsarse en el nuevo entorno de gestión multinivel. El capítulo comienza con una aproximación a la esencia de la función pública, enmarcada en un concepto de Administración redescubierto a partir de los clásicos de la Ciencia de la Administración y que permite acotar el perímetro conceptual de dicha función pública (Epígrafe 1). A continuación se realiza una evaluación del complejo entorno en que se mueven los asuntos públicos en la actualidad (Epígrafe 2), con vistas a establecer el modelo dominante de la Administración pública española en crisis y los desafíos de futuro que debe afrontar. Precisamente, esos desafíos requieren un nuevo perfil y reinvención de la función pública del Estado, máxime en un Estado multinivel de gobernanza compleja como es el nuestro (Epígrafe 4).Universidad Complutense de MadridDepto. de Ciencia Política y de la AdministraciónInstituto Complutense de Ciencia de la Administración (ICCA)Fac. de Ciencias Políticas y SociologíaTRUEpu

Public administration and human rights: an approach from the populist radical right

An administration worthy of the adjective “public” must incorporate the construction and guarantee of Human Rights into its organization, resources, and purpose. In fact, Human Rights serve as the glue or connecting element between citizenship, politics, and administrative organization. The perspective of radical populist right-wing ideology regarding administration and Human Rights, anchored in its winning formula (xenophobia, authoritarian and conservative orientation in values, and neoliberalism in economic matters), allows for several conclusions: first, there is a preference for strengthening the national level of government, impacting the system of intergovernmental relations; second, a national management of major global processes and threats, fueled by distrust in international institutions; third, a reinforcement of policies and areas related to internal order and the restriction of illegal immigration; fourth, a negative bias towards public management of welfare policies, seen as costly and demobilizing for the citizenry; fifth, an excessive trust in the market as an instrument for generating social well-being; and, finally, a preference for the public guarantee of some individual rights with a relative disregard for the guarantee of social rights.Una Administración que merezca el adjetivo de “pública” debe incorporar la construcción y garantía de los Derechos Humanos a su organización, recursos y propósito. De hecho, los Derechos Humanos se erigen en el pegamento o elemento conector entre ciudadanía, política y organización administrativa. La mirada de la derecha radical populista sobre la Administración y los Derechos Humanos, anclada en su fórmula ganadora (xenofobia, orientación autoritaria y conservadora en cuestiones de valores, y neoliberalismo en materia económica) permite extraer algunas conclusiones: preferencia por fortalecer el nivel nacional de gobierno, lo que afecta al sistema de relaciones intergubernamentales; gestión nacional de los grandes procesos y amenazas globales, lo que se nutre de una desconfianza en las instituciones internacionales; un fortalecimiento de las políticas y áreas relacionadas con el orden interno y el freno a la inmigración ilegal; un prejuicio negativo hacia la gestión pública de las políticas del bienestar, que se ven como caras y desmovilizadoras para la ciudadanía; una confianza desmedida en el mercado como instrumento para generar bienestar social; y, finalmente, una preferencia por la garantía pública de algunos derechos de carácter individual y un relativo desprecio de esa misma garantía para los derechos sociales.Instituto Complutense de Ciencia de la AdministraciónDepto. de Ciencia Política y de la AdministraciónInstituto Complutense de Ciencia de la Administración (ICCA)Fac. de Ciencias Políticas y SociologíaTRUEpu

La centralidad del estudio de la función pública en un escenario de gobernanza multinivel en crisis : A modo de introducción

El presente libro es una aportación desde la academia al estudio de la función pública desde la perspectiva de la gobernanza de nuestra sociedad, utilizando como método de análisis prioritario el del gobierno multinivel o relaciones intergubernamentales. La necesidad de estudiar la función pública, ya sea entendida en un sentido general como el conjunto de personas que prestan sus servicios profesionales en la Administración o, en sentido restringido, el personal funcionarial o, incluso más selectivamente, el segmento del personal funcionarial que ostenta el mayor poder administrativo, no es menor ni baladí, dadas las importantes funciones que desarrollan para la sociedad a la que sirven y el importante momento de cambio que esta viene sufriendo en los últimos años. No en vano, su institución matriz, la Administración pública, «vela por la equidad y la integración sociales y por el desarrollo económico y social, juega un papel transcendente en la garantía de los derechos y libertades de los ciudadanos y es un instrumento principal en el logro de la legitimidad democrática del poder público» (Arenilla, 2014), además de constituir un conector y comunicador indispensable entre la política y la sociedad.Instituto Complutense de Ciencia de la AdministraciónDepto. de Ciencia Política y de la AdministraciónFac. de Ciencias Políticas y SociologíaTRUEpu

Elecciones locales y liderazgo político en España

Elecciones locales en España y liderazgo político.Spanish local government grassroots are composed of 8.132 municipalities, which constitute fragmented, atomized, and diverse electoral spaces. The local government regulations establish an executive body, the mayor, characterized by great political and functional power ad intra and ad extra as regards the municipality. The mayor can therefore be depicted as a strong mayor with presidential overtones, thus providing an excellent base on which to project political leadership. Mayors emerge from the councilors of each municipality, who in turn are elected in competitive electoral processes, in which, on analyzing the electoral results in aggregate terms, factors such as nationalization, regionalization, and localism of the local party system appear, together with an incipient interdependence of factors, given the multilevel nature of governance in Spain. It is in this scenario that Spanish local leadership is inserted, which can be nuanced according to the importance of the municipalities and the personality of the mayor, allowing the mayor to be a true manager of interdependencies in a governance environment.Depto. de Ciencia Política y de la AdministraciónFac. de Ciencias Políticas y SociologíaTRUEpu