Longer intervals between SARS-CoV-2 infection and mRNA-1273 doses improve the neutralization of different variants of concern.

The humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern elicited by vaccination was evaluated in COVID-19 recovered individuals (Rec) separated 1-3 months (Rec2m) or 4-12 months (Rec9m) postinfection and compared to the response in naïve participants. Antibody-mediated immune responses were assessed in 66 participants by three commercial immunoassays and a SARS-CoV-2 lentiviral-based pseudovirus neutralization assay. Immunoglobulin (Ig) levels against SARS-CoV-2 spike were lower in naïve participants after two doses than in Rec after a single dose (p < 0.05). After two doses in Rec, levels of total Ig to receptor-binding domain were significantly increased in Rec9m compared to Rec2m (p < 0.001). The neutralizing potency observed in Rec9m was consistently higher than in Rec2m against variants of concern (VOCs) Alpha, Beta, Delta, and BA.1 sublineage of Omicron with 2.2-2.8-fold increases. Increasing the interval between SARS-CoV-2 infection and the vaccination with messenger RNA-based vaccines to more than 3 months generates a more efficient heterologous humoral immune response against VOCs by allowing enough time to mount a strong recall memory B cell response.

Immune response and reactogenicity after immunization with two-doses of an experimental COVID-19 vaccine (CVnCOV) followed by a third-fourth shot with a standard mRNA vaccine (BNT162b2): RescueVacs multicenter cohort study.

Background: There is no evidence to date on immunogenic response among individuals who participated in clinical trials of COVID-19 experimental vaccines redirected to standard national vaccination regimens. Methods: This multicentre, prospective controlled cohort study included subjects who received a COVID-19 experimental vaccine (CVnCoV)(test group, TG) - and unvaccinated subjects (control group, CG), selected among individuals to be vaccinated according to the Spanish vaccination program. All study subjects received BNT162b2 as a standard national vaccination schedule, except 8 (from CG) who received mRNA-1273 and were excluded from immunogenicity analyses. Anti-RBD antibodies level and neutralising titres (NT50) against G614, Beta, Mu, Delta and Omicron variants were analysed. Reactogenicity was also assessed. Findings: 130 participants (TG:92; CG:38) completed standard vaccination. In TG, median (IQR) of anti-RBD antibodies after first BNT162b2 dose were 10740·0 BAU/mL (4466·0-12500) compared to 29·8 BAU/mL (14·5-47·8) in CG (p <0·0001). Median NT50 (IQR) of G614 was 2674·0 (1865·0-3997·0) in TG and 63·0 (16·0-123·1) in CG (p <0·0001). After second BNT162b2 dose, anti-RBD levels increased to ≥12500 BAU/mL (11625·0-12500) in TG compared to 1859·0 BAU/mL (915·4-3820·0) in CG (p <0·0001). NT50 was 2626·5 (1756·0-5472·0) and 850·4 (525·1-1608·0), respectively (p <0·0001). Variant-specific (Beta, Mu, Omicron) response was also assessed. Most frequent adverse reactions were headache, myalgia, and local pain. No severe AEs were reported. Interpretation: Heterologous BNT162b2 as third and fourth doses in previously suboptimal immunized individuals elicit stronger immune response than that obtained with two doses of BNT162b2. This apparent benefit was also observed in variant-specific response. No safety concerns arose. Funding: Partly funded by the Institute of Health Carlos-III and COVID-19 Fund, co-financed by the European Regional Development Fund (FEDER) "A way to make Europe".

Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study.

Background: The CombiVacS study was designed to assess immunogenicity and reactogenicity of the heterologous ChAdOx1-S/BNT162b2 combination, and 14-day results showed a strong immune response. The present secondary analysis addresses the evolution of humoral and cellular response up to day 180. Methods: Between April 24 and 30, 2021, 676 adults primed with ChAdOx1-S were enrolled in five hospitals in Spain, and randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Individuals from CG received BNT162b2 as second dose and also on day 28, as planned based on favourable results on day 14. Humoral immunogenicity, measured by immunoassay for SARS-CoV-2 receptor binding domain (RBD), antibody functionality using pseudovirus neutralisation assays for the reference (G614), Alpha, Beta, Delta, and Omicron variants, as well as cellular immune response using interferon-γ and IL-2 immunoassays were assessed at day 28 after BNT162b2 in both groups, at day 90 (planned only in the interventional group) and at day 180 (laboratory data cut-off on Nov 19, 2021). This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739). Findings: In this secondary analysis, 664 individuals (441 from IG and 223 from CG) were included. At day 28 post vaccine, geometric mean titres (GMT) of RBD antibodies were 5616·91 BAU/mL (95% CI 5296·49-5956·71) in the IG and 7298·22 BAU/mL (6739·41-7903·37) in the CG (p < 0·0001). RBD antibodies titres decreased at day 180 (1142·0 BAU/mL [1048·69-1243·62] and 1836·4 BAU/mL [1621·62-2079·62] in the IG and CG, respectively; p < 0·0001). Neutralising antibodies also waned from day 28 to day 180 in both the IG (1429·01 [1220·37-1673·33] and 198·72 [161·54-244·47], respectively) and the CG (1503·28 [1210·71-1866·54] and 295·57 [209·84-416·33], respectively). The lowest variant-specific response was observed against Omicron-and Beta variants, with low proportion of individuals exhibiting specific neutralising antibody titres (NT50) >1:100 at day 180 (19% and 22%, respectively). Interpretation: Titres of RBD antibodies decay over time, similar to homologous regimes. Our findings suggested that delaying administration of the second dose did not have a detrimental effect after vaccination and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180. Funding: Funded by Instituto de Salud Carlos III (ISCIII).

Impaired Antibody-Dependent Cellular Cytotoxicity in a Spanish Cohort of Patients With COVID-19 Admitted to the ICU.

SARS-CoV-2 infection causes COVID-19, ranging from mild to critical disease in symptomatic subjects. It is essential to better understand the immunologic responses occurring in patients with the most severe outcomes. In this study, parameters related to the humoral immune response elicited against SARS-CoV-2 were analysed in 61 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centres in Madrid, Spain, during the first pandemic peak between April and June 2020. Subjects were allocated as mild patients without hospitalization, severe patients hospitalized or critical patients requiring ICU assistance. Critical patients showed significantly enhanced levels of B cells with memory and plasmablast phenotypes, as well as higher levels of antibodies against SARS-CoV-2 with neutralization ability, which were particularly increased in male gender. Despite all this, antibody-dependent cell-mediated cytotoxicity was defective in these individuals. Besides, patients with critical COVID-19 also showed increased IgG levels against herpesvirus such as CMV, EBV, HSV-1 and VZV, as well as detectable CMV and EBV viremia in plasma. Altogether, these results suggest an enhanced but ineffectual immune response in patients with critical COVID-19 that allowed latent herpesvirus reactivation. These findings should be considered during the clinical management of these patients due to the potential contribution to the most severe disease during SARS-CoV-2 infection.

La profesionalización de los docentes de la educación superior: implicaciones en el desarrollo social desde su competitividad / Professionalism of the teaching staff from higher education: implications in the social development taking into account their competence

El propósito de este artículo es analizar las implicaciones sociales de la labor de los profesores universitarios desde la relación que se establece entre el claustro y los empleadores en la búsqueda de una universidad competitiva, innovadora y sostenible. Así, para que dicha universidad perdure en el tiempo, tiene que involucrar a todos sus académicos, estudiantes y trabajadores en el mejoramiento de su capital humano y satisfacer las necesidades del presente desde varias perspectivas. La competitividad del docente es una de las cualidades necesarias para proteger su prestigio académico y educativo, lo cual conlleva a un futuro sostenible donde la preparación pedagógica del claustro universitario juega un importante rol.

The purpose of this work is to analyze the social implications of the university professors work from the relationship emerging between the staff and the employers in the search of a competitive, innovative and sustainable university. Thus, for this university to lasts in time, it has to involve all its academics, students and workers in the improvement of the human capital and to satisfy the needs of the present from several perspectives. Competence of the teaching staff is one of the necessary qualities to protect its academic staff and educational prestige, which bears to a sustainable future where the pedagogical training of the university staff plays an important role.

Dispensación de medicamentos en farmacias y establecimientos asistenciales del sector público / Dispensing of medicines in pharmacies and public health-care institutions

INTRODUCCION: Existe un conjunto de variables que están asociadas a los resultados de la política nacional de medicamentos implementada en los últimos años.OBJETIVO: Identificar variables y nuevas estrategias que permitan mejorar el acceso de la población a los medicamentos y promuevan su uso racional.METODOS: Se utilizó un enfoque descriptivo y cuantitativo basado en encuestas realizadas sobre una muestra probabilística de etapas múltiples, que aseguró la selección aleatoria de la población relevada en todas las fases del proceso. La investigación contuvo dos módulos: a) encuestas en farmacias y b) encuestas en lugares de dispensación de medicamentos pertenecientes a establecimientos asistenciales del sector público de toda la Argentina. En ambos casos, se encuestó a los compradores y beneficiarios de medicamentos, así como a los vendedores y responsables de la dispensación.RESULTADOS: La proporción de recetas que incluyen el nombre genérico del medicamento ha disminuido en las farmacias, mientras que alcanza el 95% en los establecimientos públicos.CONCLUSIONES: Las características de la compra y la proporción de entrega sin receta de medicamentos éticos resultan preocupantes. Tanto el sector público como el privado requieren acciones de fortalecimiento para garantizar el acceso y el uso racional de medicamentos.

INTRODUCTION: There are several variables related to the results of the national drug policy, implemented by health authorities in Argentina during the last years.OBJECTIVE: To identify variables and new strategies that help to improve the access to the medicines and promote its rational use.METHODS: A descriptive and quantitative approach was used. The surveys were conducted through a multistage probabilistic sample, ensuring a random selection of the population during the whole process. The research included two modules: a) surveys in pharmacies, and b) surveys in public health-care institutions dispensing medicines all around the country. In both cases the people surveyed were, on one side, buyers and beneficiaries, and on the other, sellers and persons in charge of the dispensing.RESULTS: The proportion of prescriptions including the generic name of the drug has been reduced in pharmacies, while it reaches 95% in public health-care institutions.CONCLUSIONS: The features of the purchase and the rate of delivery of ethical drugs without prescription are distressing. Both public and private sectors require appropriate actions in order to guarantee access to and rational use of medicines.

Dispensación de medicamentos en farmacias y establecimientos asistenciales del sector público / Dispensing of medicines in pharmacies and public health-care institutions

INTRODUCCION: Existe un conjunto de variables que están asociadas a los resultados de la política nacional de medicamentos implementada en los últimos años.OBJETIVO: Identificar variables y nuevas estrategias que permitan mejorar el acceso de la población a los medicamentos y promuevan su uso racional.METODOS: Se utilizó un enfoque descriptivo y cuantitativo basado en encuestas realizadas sobre una muestra probabilística de etapas múltiples, que aseguró la selección aleatoria de la población relevada en todas las fases del proceso. La investigación contuvo dos módulos: a) encuestas en farmacias y b) encuestas en lugares de dispensación de medicamentos pertenecientes a establecimientos asistenciales del sector público de toda la Argentina. En ambos casos, se encuestó a los compradores y beneficiarios de medicamentos, así como a los vendedores y responsables de la dispensación.RESULTADOS: La proporción de recetas que incluyen el nombre genérico del medicamento ha disminuido en las farmacias, mientras que alcanza el 95% en los establecimientos públicos.CONCLUSIONES: Las características de la compra y la proporción de entrega sin receta de medicamentos éticos resultan preocupantes. Tanto el sector público como el privado requieren acciones de fortalecimiento para garantizar el acceso y el uso racional de medicamentos.

INTRODUCTION: There are several variables related to the results of the national drug policy, implemented by health authorities in Argentina during the last years.OBJECTIVE: To identify variables and new strategies that help to improve the access to the medicines and promote its rational use.METHODS: A descriptive and quantitative approach was used. The surveys were conducted through a multistage probabilistic sample, ensuring a random selection of the population during the whole process. The research included two modules: a) surveys in pharmacies, and b) surveys in public health-care institutions dispensing medicines all around the country. In both cases the people surveyed were, on one side, buyers and beneficiaries, and on the other, sellers and persons in charge of the dispensing.RESULTS: The proportion of prescriptions including the generic name of the drug has been reduced in pharmacies, while it reaches 95% in public health-care institutions.CONCLUSIONS: The features of the purchase and the rate of delivery of ethical drugs without prescription are distressing. Both public and private sectors require appropriate actions in order to guarantee access to and rational use of medicines.

Gestantes epilépticas, evolución final y otras variables de riesgo evaluadas en una consulta interdisciplinaria regional / Epileptic pregnants, final course and other risk variables assessed in regional interdisciplinary consultation

La epilepsia es la segunda entidad neurológica más frecuente durante la gestación, con prevalencias de 34 / 1 000 embarazos, su manejo muchas veces es ineficaz en la atención primaria. OBJETIVOS: describir variables epidemiológicas capaces de influir en la evolución final de la gestante epiléptica. Se valoran: edad, gestaciones previas según número de hijos, otras patologías asociadas, fecha de parto atendiendo a evolución obstétrica final. MÉTODOS: se realizó una cohorte de 5 años, en consulta clínico/obstétrica regional del municipio San Antonio de los Baños, provincia Habana, se muestrearon opináticamente 2 grupos de 50 pacientes, A: epilépticas, B: sanas. RESULTADOS: en A el 70 por ciento presentó edades entre 30 y 35 años, para una media de 33,5 con tendencia a la derecha según distribución gaussiana. El 64 por ciento de las no epilépticas tuvo más de 3 gestaciones previas, el 70 por ciento del grupo A presentó un solo hijo sin asociación entre variables según Chi 2. No existieron diferencias entre grupos en cuanto a patologías asociadas al embarazo predominado la hipertensión gestacional globalmente (27 por ciento), con discreta tendencia en el grupo A de aparecer tempranamente en el 3er. trimestre. Ambos grupos de pacientes tuvieron buena evolución final de la gestación, el mayor número de epilépticas paren antes de las 40 sem sin firme nivel de evidencia que lo justifique. CONCLUSIONES: las epilépticas se embarazan menos veces y más tardíamente, tienen pocos hijos, sin diferencias significativas en cuanto a patologías asociadas que limiten el normal desarrollo de la gestación, existe tendencia a acortar el período gestacional sin fundamento demostrado según las evidencias.

Epilepsy is the second more frequent neurologic entity during pregnancy with prevalences of 3-4 / 1 000 pregnancies, its management often is ineffective in primary care. OBJECTIVES: to describe the epidemiological variables able to influence in final course of epileptic pregnant. In assessment are included: age, previous pregnants according children number, other associated pathologies, and labor date considering the final obstetric course. METHODS: the was a 5-years cohort in the clinical/obstetrical regional consultation of San Antonio de los Baños, Havana province; according criteria two groups of 50 patients each were sampled, A: epileptic, B; healthy. RESULTS: in group A the 70 percent was aged between 30-35 for a mean of 33,5 with a right trend according Gauss' distribution. The 64 percent of that non-epileptic had more of three previous pregnancies; the 70 percent of A group had a only child without association among variables by Chi ². There were not differences among the groups regards the pathologies associated to pregnancy with a predominance of gestational high blood pressure as a whole (27 percent) with a discrete trend in A group to appear early during the third trimester. Both groups of patients had a good final course of pregnancy; the great number of epileptic gave birth before the 40 weeks without a solid level of evidence justifying this situation. CONCLUSIONS: pregnant have fewer pregnancies and belatedly, have fewer children with significant differences regards associated pathologies limiting the normal pregnancy development; there is a trend to shorten the gestational period without a basis demonstrated according evidences.

Gestantes epilépticas, evolución final y otras variables de riesgo evaluadas en una consulta interdisciplinaria regional / Epileptic pregnants, final course and other risk variables assessed in regional interdisciplinary consultation

La epilepsia es la segunda entidad neurológica más frecuente durante la gestación, con prevalencias de 34 / 1 000 embarazos, su manejo muchas veces es ineficaz en la atención primaria. OBJETIVOS: describir variables epidemiológicas capaces de influir en la evolución final de la gestante epiléptica. Se valoran: edad, gestaciones previas según número de hijos, otras patologías asociadas, fecha de parto atendiendo a evolución obstétrica final. MÉTODOS: se realizó una cohorte de 5 años, en consulta clínico/obstétrica regional del municipio San Antonio de los Baños, provincia Habana, se muestrearon opináticamente 2 grupos de 50 pacientes, A: epilépticas, B: sanas. RESULTADOS: en A el 70 por ciento presentó edades entre 30 y 35 años, para una media de 33,5 con tendencia a la derecha según distribución gaussiana. El 64 por ciento de las no epilépticas tuvo más de 3 gestaciones previas, el 70 por ciento del grupo A presentó un solo hijo sin asociación entre variables según Chi 2. No existieron diferencias entre grupos en cuanto a patologías asociadas al embarazo predominado la hipertensión gestacional globalmente (27 por ciento), con discreta tendencia en el grupo A de aparecer tempranamente en el 3er. trimestre. Ambos grupos de pacientes tuvieron buena evolución final de la gestación, el mayor número de epilépticas paren antes de las 40 sem sin firme nivel de evidencia que lo justifique. CONCLUSIONES: las epilépticas se embarazan menos veces y más tardíamente, tienen pocos hijos, sin diferencias significativas en cuanto a patologías asociadas que limiten el normal desarrollo de la gestación, existe tendencia a acortar el período gestacional sin fundamento demostrado según las evidencias

Epilepsy is the second more frequent neurologic entity during pregnancy with prevalences of 3-4 / 1 000 pregnancies, its management often is ineffective in primary care. OBJECTIVES: to describe the epidemiological variables able to influence in final course of epileptic pregnant. In assessment are included: age, previous pregnants according children number, other associated pathologies, and labor date considering the final obstetric course. METHODS: the was a 5-years cohort in the clinical/obstetrical regional consultation of San Antonio de los Ba±os, Havana province; according criteria two groups of 50 patients each were sampled, A: epileptic, B; healthy. RESULTS: in group A the 70 percent was aged between 30-35 for a mean of 33,5 with a right trend according Gauss' distribution. The 64 percent of that non-epileptic had more of three previous pregnancies; the 70 percent of A group had a only child without association among variables by Chi ². There were not differences among the groups regards the pathologies associated to pregnancy with a predominance of gestational high blood pressure as a whole (27 percent) with a discrete trend in A group to appear early during the third trimester. Both groups of patients had a good final course of pregnancy; the great number of epileptic gave birth before the 40 weeks without a solid level of evidence justifying this situation. CONCLUSIONS: pregnant have fewer pregnancies and belatedly, have fewer children with significant differences regards associated pathologies limiting the normal pregnancy development; there is a trend to shorten the gestational period without a basis demonstrated according evidences

Gestantes epilépticas, evolución final y otras variables de riesgo evaluadas en una consulta interdisciplinaria regional / Epileptic pregnants, final course and other risk variables assessed in regional interdisciplinary consultation

La epilepsia es la segunda entidad neurológica más frecuente durante la gestación, con prevalencias de 34 / 1 000 embarazos, su manejo muchas veces es ineficaz en la atención primaria. OBJETIVOS: describir variables epidemiológicas capaces de influir en la evolución final de la gestante epiléptica. Se valoran: edad, gestaciones previas según número de hijos, otras patologías asociadas, fecha de parto atendiendo a evolución obstétrica final. MÉTODOS: se realizó una cohorte de 5 años, en consulta clínico/obstétrica regional del municipio San Antonio de los Baños, provincia Habana, se muestrearon opináticamente 2 grupos de 50 pacientes, A: epilépticas, B: sanas. RESULTADOS: en A el 70 por ciento presentó edades entre 30 y 35 años, para una media de 33,5 con tendencia a la derecha según distribución gaussiana. El 64 por ciento de las no epilépticas tuvo más de 3 gestaciones previas, el 70 por ciento del grupo A presentó un solo hijo sin asociación entre variables según Chi 2. No existieron diferencias entre grupos en cuanto a patologías asociadas al embarazo predominado la hipertensión gestacional globalmente (27 por ciento), con discreta tendencia en el grupo A de aparecer tempranamente en el 3er. trimestre. Ambos grupos de pacientes tuvieron buena evolución final de la gestación, el mayor número de epilépticas paren antes de las 40 sem sin firme nivel de evidencia que lo justifique. CONCLUSIONES: las epilépticas se embarazan menos veces y más tardíamente, tienen pocos hijos, sin diferencias significativas en cuanto a patologías asociadas que limiten el normal desarrollo de la gestación, existe tendencia a acortar el período gestacional sin fundamento demostrado según las evidencias (AU)

Epilepsy is the second more frequent neurologic entity during pregnancy with prevalences of 3-4 / 1 000 pregnancies, its management often is ineffective in primary care. OBJECTIVES: to describe the epidemiological variables able to influence in final course of epileptic pregnant. In assessment are included: age, previous pregnants according children number, other associated pathologies, and labor date considering the final obstetric course. METHODS: the was a 5-years cohort in the clinical/obstetrical regional consultation of San Antonio de los Ba±os, Havana province; according criteria two groups of 50 patients each were sampled, A: epileptic, B; healthy. RESULTS: in group A the 70 percent was aged between 30-35 for a mean of 33,5 with a right trend according Gauss' distribution. The 64 percent of that non-epileptic had more of three previous pregnancies; the 70 percent of A group had a only child without association among variables by Chi ². There were not differences among the groups regards the pathologies associated to pregnancy with a predominance of gestational high blood pressure as a whole (27 percent) with a discrete trend in A group to appear early during the third trimester. Both groups of patients had a good final course of pregnancy; the great number of epileptic gave birth before the 40 weeks without a solid level of evidence justifying this situation. CONCLUSIONS: pregnant have fewer pregnancies and belatedly, have fewer children with significant differences regards associated pathologies limiting the normal pregnancy development; there is a trend to shorten the gestational period without a basis demonstrated according evidences (AU)