Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines.

OBJECTIVE: The aim of this study was to assess the immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibody titers after the primary regimen of 2 doses. METHODS: Patients with RA with no seroconversion after 2 doses of SARS-CoV-2 vaccine and who received a third dose of either an mRNA or vector-based vaccine were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity, and T cell responses were assessed after the third dose. RESULTS: A total of 21 nonresponder patients were included. At the time of vaccination, 29% were receiving glucocorticoids and 85% biologic disease-modifying antirheumatic drugs (including 6 taking abatacept [ABA] and 4 taking rituximab [RTX]). The majority (95%) received the BNT162b2 vaccine and only one of them received the ChAdOx1 nCoV-19 vaccine. After the third dose, 91% of the patients presented detectable anti-SARS-CoV-2 IgG and 76% showed neutralizing activity. Compared to other treatments, ABA and RTX were associated with the absence of neutralizing activity in 4 out of 5 (80%) patients and lower titers of neutralizing antibodies (median 3, IQR 0-20 vs 8, IQR 4-128; P = 0.20). Specific T cell response was detected in 41% of all patients after the second dose, increasing to 71% after the third dose. The use of ABA was associated with a lower frequency of T cell response (33% vs 87%, P = 0.03). CONCLUSION: In this RA cohort, 91% of patients who failed to seroconvert after 2 doses of SARS-CoV-2 vaccine presented detectable anti-SARS-CoV-2 IgG after a third dose. The use of ABA was associated with a lower frequency of specific T cell response.

Immunogenicity and reactogenicity of heterologous immunization against SARS CoV-2 using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV, and mRNA-1273.

Heterologous vaccination against coronavirus disease 2019 (COVID-19) provides a rational strategy to rapidly increase vaccination coverage in many regions of the world. Although data regarding messenger RNA (mRNA) and ChAdOx1 vaccine combinations are available, there is limited information about the combination of these platforms with other vaccines widely used in developing countries, such as BBIBP-CorV and Sputnik V. Here, we assess the immunogenicity and reactogenicity of 15 vaccine combinations in 1,314 participants. We evaluate immunoglobulin G (IgG) anti-spike response and virus neutralizing titers and observe that a number of heterologous vaccine combinations are equivalent or superior to homologous schemes. For all cohorts in this study, the highest antibody response is induced by mRNA-1273 as the second dose. No serious adverse events are detected in any of the schedules analyzed. Our observations provide rational support for the use of different vaccine combinations to achieve wide vaccine coverage in the shortest possible time.

Rational design of PIN1 inhibitors for cancer treatment based on conformational diversity analysis and docking based virtual screening.

The parvulin PIN1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1), is the only enzyme capable of isomerizing prolines of phospho-Serine/Threonine-Proline motifs. PIN1 binds to a subset of proteins and plays an essential role in regulating protein function post-phosphorylation control. Furthermore, the activity of PIN1 regulates the outcome of the signalling of proline-directed kinases (e.g. MAPK, CDK, or GSK3) and thus regulates cell proliferation and cell survival. For these reasons, PIN1 inhibitors are interesting since they may have therapeutic implications for cancer. Several authors have already reported that the non-structural point mutation Trp34Ala prevents PIN1 from interacting with its downstream effector proteins. In this work, we characterized PIN1 structurally, intending to explore new inhibition targets for the rational design of pharmacological activity compounds. Through a conformational diversity analysis of PIN1, we identified and characterized a highly specific druggable pocket around the residue Trp34. This pocket was used in a high-throughput docking screening of 450,000 drug-like compounds, and the top 10 were selected for re-docking studies on the previously used conformers. Finally, we evaluated the binding of each compound by thermal shift assay and found four molecules with a high affinity for PIN1 and potential inhibitory activity. Through this strategy, we achieved novel drug candidates with the ability to interfere with the phosphorylation-dependent actions of PIN1 and with potential applications in the treatment of cancer.Communicated by Ramaswamy H. Sarma.

Detección de SARS-CoV-2 en contactos estrechos asintomáticos de casos confirmados por diagnóstico molecular, provincia de Buenos Aires, Argentina / Detection of SARS-CoV-2 in asymptomatic close contacts of cases confirmed by molecular diagnosis, Buenos Aires province, Argentina

Resumen La detección de SARS-CoV-2 y su implicancia en el diagnóstico de COVID-19 han sido muy debatidas en la pandemia. El objetivo de este estudio fue evaluar el costo/beneficio de la detección de SARS-CoV-2 en contactos estrechos asintomáticos (CE) mediante el uso de distintas pruebas de diagnóstico molecular. Se estudiaron 51 CE de personas con diagnóstico de SARS-CoV-2 confirmado por RTqPCR, clasificadas por el umbral de ciclos (Ct) (<20, entre 20 y 30 y >30) en hospitales públicos de la provincia de Buenos Aires. Del total de contactos estudiados el 15,7% resultó confirmado para SARS-CoV-2; no hubo contactos positivos de casos con Ct>30. La cantidad de contactos positivos de casos con Ct<20 fue significativamente mayor que la de casos con Ct>20. Las muestras con Ct<20 se asociaron a una carga viral estimada de entre uno a cuatro órdenes de magnitud de diferencia con los rangos de Ct>20. Un 13,7% de contactos positivos fueron casos con Ct<20. De las muestras positivas confirmadas por PCR, correspondientes a la semana epidemiológica 1 de 2021 (SE1), sólo un 19,35% correspondían a muestras con Ct<20 y un 50,7% con Ct entre 20 y 30. Estos datos muestran un incremento de sólo un 3,7% de casos detectados. El esfuerzo por parte del sistema de salud pública para esta estrategia, con bajo poder predictivo, puede tener un efecto negativo para el cumplimiento del aislamiento de los contactos y podría generar una demora en los resultados de los casos sospechosos, sin aportar significativamente en el control de la pandemia.

Abstract The detection of SARS-CoV-2 and its implication in the diagnosis of COVID-19 have been highly debated in the pandemic. The objective of this study was to evaluate the cost/benefit of detecting SARS-CoV-2 in asymptomatic close contacts (CC) using different molecular diagnostic tests. A total of 51 CC of people with a diagnosis of SARS-CoV-2 confirmed by RTqPCR, classified by the cycle threshold (Ct) (<20, between 20 and 30 and >30), were studied in public hospitals in the Province of Buenos Aires. Of the total contacts studied, 15.7% were confirmed for SARS-CoV-2; there were no positive contacts of cases with Ct>30 positive. The number of positive contacts of cases with Ct<20 was significantly higher than that of cases with Ct>20. Samples with Ct<20 were associated with an estimated viral load of one to four orders of magnitude difference with Ct ranges >20. A total of 13.7% of positive close contacts were from cases with Ct<20. When studying positive samples with confirmed diagnosis by PCR, corresponding to 1 epidemiological week of 2021 (EW1), only 19.35% corresponded to samples with Ct<20 and 50.7% with Ct between 20 and 30. From these data it is shown that with the CC test only 3.7% of the cases were detected. The effort by the public health system for this strategy, with low predictive power, may have a negative effect on the fulfillment of the isolation of contacts and could generate a delay in the results of suspected cases, without contributing significantly to controlling the pandemic.

Resumo A detecção do SARS-CoV-2 e seu envolvimento no diagnóstico da COVID-19 têm sido muito discutidos durante a pandemia. O objetivo desse estudo foi avaliar a relação custo/benefício na detecção de SARSCoV- 2 em casos de contatos próximos assintomático (CP), por meio do uso de diferentes testes de diagnóstico molecular. Foram estudados 51 casos de CP de pessoas com diagnóstico de SARS-CoV-2 confirmado pelo RTqPCR, sendo classificados pelo limiar de ciclos (Ct) (<20, entre 20 e 30 e >30), em hospitais públicos da província de Buenos Aires. Do total de contatos estudados, 15,7% foram confirmados para SARS-CoV-2, não houve contatos positivos de casos com Ct>30. O número de contatos positivos de casos com Ct<20, foi significativamente maior que os casos com Ct>20. As amostras com Ct<20 foram associadas a uma carga viral estimada de uma a quatro ordens de magnitude de diferença com os intervalos de Ct>20. Dos casos positivos, 13,7% foram com Ct<20. Das amostras positivas confirmadas por PCR, correspondentes à semana epidemiológica 1 de 2021 (SE1), apenas 19,35% correspondiam a amostras com Ct>20 e 50,7% com Ct entre 20 e 30. Esses dados mostram incremento de apenas 3,7% de casos detectados. O esforço por parte do sistema de saúde pública para essa estratégia, com baixo poder preditivo, pode ter um efeito negativo no cumprimento do isolamento dos contatos e poderia gerar uma demora nos resultados dos casos suspeitos, sem contribuir significativamente para o controle da pandemia.

Effectiveness of the first component of Gam-COVID-Vac (Sputnik V) on reduction of SARS-CoV-2 confirmed infections, hospitalisations and mortality in patients aged 60-79: a retrospective cohort study in Argentina.

BACKGROUND: A first-dose of various vaccines provides acceptable protection against infections by SARS-CoV-2 and evolution to the most severe forms of COVID-19. The recombinant adenovirus (rAd)-based vaccine, Gam-COVID-Vac (Sputnik V), was proven efficacious but information about effectiveness in the real-world setting is lacking. The aim of our study was to investigate the association between the rollout of the first component (rAd26) of Gam-COVID-Vac and PCR-positive tests, hospitalisations and deaths. METHODS: We conducted a retrospective cohort study which analyzed individuals aged 60-79 who self-registered in the online vaccination system of the Province of Buenos Aires, Argentina, from December 29, 2020 to March 21, 2021. Exclusion criteria were having a previous positive RT-PCR or antigen tests for SARS-CoV-2, having received other vaccines, or two doses of any vaccine.Proportions of new laboratory-confirmed SARS-CoV-2 infections, hospitalisations and deaths until 83 days of vaccination were compared between vaccinated and unvaccinated subjects. Vaccine effectiveness for the three outcomes was calculated as (1-OR) × 100. Kaplan-Meier cumulative incidence curves were constructed. FINDINGS: During the study period 415995 registered subjects received the first component of Gam-COVID-Vac; 40387 belonged to the 60-79 age group, and were compared to 38978 unvaccinated. Vaccine effectiveness for preventing laboratory-confirmed infections was 78•6% [CI95% 74·8 - 81·7]; and for reducing hospitalizations and deaths was, respectively, 87·6% [CI95% 80·3 - 92·2] and 84·8% [CI95% 75·0 - 90·7]. Effectiveness was high across all subgroups. INTERPRETATION: Similarly to other vaccines, the administration of one dose of Gam-COVID-Vac was effective for a wide range of COVID-19-related outcomes. FUNDING: This study did not receive any funding.

Sputnik V vaccine elicits seroconversion and neutralizing capacity to SARS-CoV-2 after a single dose.

Massive vaccination offers great promise for halting the global COVID-19 pandemic. However, the limited supply and uneven vaccine distribution create an urgent need to optimize vaccination strategies. We evaluate SARS-CoV-2-specific antibody responses after Sputnik V vaccination of healthcare workers in Argentina, measuring IgG anti-spike titers and neutralizing capacity after one and two doses in a cohort of naive or previously infected volunteers. By 21 days after receiving the first dose of the vaccine, 94% of naive participants develop spike-specific IgG antibodies. A single Sputnik V dose elicits higher antibody levels and virus-neutralizing capacity in previously infected individuals than in naive ones receiving the full two-dose schedule. The high seroconversion rate after a single dose in naive participants suggests a benefit of delaying administration of the second dose to increase the number of people vaccinated. The data presented provide information for guiding public health decisions in light of the current global health emergency.

Impact of vaccines against COVID-19 on new SARS-COV2 infections in health care workers of the Province of Buenos Aires / Impacto de vacunación covid-19 en las infecciones por sars-cov-2 en personal de salud de la provincia de buenos aires

RESUMEN INTRODUCCIÓN : La vacunación en la provincia de Buenos Aires inició con personal de salud (PS). El objetivo de este trabajo es evaluar el impacto de la vacunación sobre la evolución de los casos de infección por SARS-CoV-2 en el PS, comparado con la de la población general (PG). MÉTODOS : Estudio obsewacional descriptivo de series temporales de casos confirmados de COVID-19, entre abril de 2020 y marzo de 2021. Se utilizó el sistema de información VacunatePBA y el SNVS. Se tomó el grado de inmunización a 14 días de la aplicación de la vacuna. RESULTADOS : A partir de septiembre de 2020, el número de casos disminuyó en el PS, en comparación con la PG. Para fines de febrero de 2021 estaba inmunizado con primera dosis (PD) el 42% del PS y con segunda dosis (SD) el 24%, mientras que en PG solo estaba inmunizado el 0,06% con PD y nadie SD. En marzo de 2021 mientras la cantidad de casos en PG (con 2% inmunizada) aumentó un 10% con respecto a febrero, en PS disminuyó un 35% (95% de esa población inmunizada). Esto indica una disminución significativa entre los nuevos casos de febrero y de marzo en PS (p <0,00001). DISCUSIÓN : A partir del inicio de la vacunación contra COVID-19 a finales de diciembre 2020, se muestra una disminución de casos nuevos de COVID-19 en PS. Este trabajo describe una disminución relativa de los casos en PS luego de la vacunación en la provincia de Buenos Aires y aporta los primeros datos del país sobre el impacto de las vacunas contra COVID-19.

ABSTRACT INTRODUCTION : The vaccination in the province of Buenos Aires has initiated with the health care workers (HCW). The present work aims to evaluate the impact of vaccination on the evolution of confirmed SARS- CoV2 cases in HCW compared to that of the general population (GP). METHODS : The study design is descriptive observational of series were developed confirmed cases, period April 2020 to March 2021. The Sistema Nacional de Vigilancia en Salud (SNVS), and VacunatePBA were used. The grade immunization was estimated at 14 days from the application of the first dose. RESULTS : As of September, the number of cases begins to decrease more sharply in HCW than in the general population. By February 2021, 42% of the HCW had been immunized with the first dose (FD) and 24% with the second dose (SD), while in GP only 0.06% had been immunized with FD and 0% of SD. In March, while the number of GP cases increased by 10% compared to February (only 2% immunized), HCW decreased by 35% (95% immunized). This indicates a significant decrease between the new cases of February and March in HCW (p-value <0.00001). DISCUSSION: Since the introduction of COVID-19 vaccines at the end of December in different countries, a decrease in new cases of COVID-19 in HCW has begun to be reported. The present work describes a relative decrease in HCW cases in a post-vaccination context in the province of Buenos Aires, providing the first data in the country on the impact of COVID-19 vaccines on HCW.

Impact of vaccines against COVID-19 on the incidence of new SARS-COV2 infections in health care workers of the Province of Buenos Aires / Impacto de la aplicación de vacunas contra COVID-19 sobre la incidencia de nuevas infecciones por SARS-COV-2 en PS de la Provincia de Buenos Aires / O impacto da aplicação de vacinas contra a COVID-19 sobre a incidência de novas infeções pelo SARS ­COV-2 em trabalhadores da saúde da Provincia de Buenos Aires

Introduction. The vaccination plan of the province of Buenos Aires has prioritized the groups with the highest epidemiological risk, initiating the immunization process on Health Care Worker (HCP). The present work aims to evaluate the impact of vaccination on the mean evolution of new SARS-Cov-2 cases in HCP compared to that of the general population. Methodology. Information on confirmed cases was obtained from the Sistema Nacional de Vigilancia en Salud, period April/2020 to March/2021. The number of vaccinated used the base of the VacunatePBA system. Results. As of September, the number of cases begins to decrease more sharply in HCP than in the general population. This trend is consolidated with the beginning of the vaccination plan. By February 2021, 42% of the HCP had been immunized with the first dose and 24% with the second dose. It is observed that, in March, while the number of cases in the General Population increased by 10% compared to February, HCP decreased by 35%. This indicates a significantly more pronounced decrease in HCP (p-value <0.00001). Discussion. Since the introduction of the COVID-19 vaccine at the end of december in different countries, a decrease in the incidence of new cases of SARS-CoV-2 infection in HCP has begun to be reported, coinciding with the findings of the present study. Our study provides the first data in the country on the impact of COVID-19 vaccines on HCP.

Introducción. El plan de vacunación de la provincia de Buenos Aires ha priorizado los grupos de mayor riesgo epidemiológico, iniciando el proceso de inmunización sobre el Personal de Salud (PS).El presente trabajo tiene por objetivo evaluar el impacto de la vacunación sobre la evolución media de nuevos casos SARS-Cov-2 en PS comparada con la de la población general. Metodología. La información de los casos confirmados se obtuvo del Sistema Nacional de Vigilancia de la Salud, período abril/2020 a marzo/2021. La cantidad de vacunados utilizó la base del sistema VacunatePBA. Resultados. A partir de septiembre, el número de casos comienza a disminuir más pronunciadamente en PS que en la población general. Esta tendencia se consolida con el comienzo del plan de vacunación. Para febrero de 2021 se han inmunizado con la primera dosis el 42% del PS y con la segunda dosis el 24%. Se observa que, en marzo, mientras la cantidad de casos de la Población General aumenta un 10% respecto a febrero, PS disminuye un 35%. Esto indica un descenso significativamente más pronunciado en PS (p-valor < 0.00001). Discusión. A partir de la introducción de la vacuna contra COVID-19 a finales de diciembre en distintos países, se ha comenzado a reportar una baja de la incidencia de nuevos casos de infección por SARS-CoV-2 en PS, coincidente con los hallazgos del presente estudio. Nuestro estudio aporta los primeros datos del país sobre el impacto de las vacunas COVID-19 en PS.

DETECTION OF SARS-CoV-2 IN ASYMPTOMATIC CLOSE CONTACTS OF CASES CONFIRMED BY MOLECULAR DIAGNOSIS, BUENOS AIRES PROVINCE, ARGENTINA / DETECCIÓN DE SARS-CoV-2 EN CONTACTOS ESTRECHOS ASINTOMÁTICOS DE CASOS CONFIRMADOS POR DIAGNÓSTICO MOLECULAR, PROVINCIA DE BUENOS AIRES, ARGENTINA / DETECÇÃO DE SARS-CoV-2 EM CONTATOS ESTREITOS ASSIMTOMÁTICOS DE CASOS CONFIRMADOS POR DIAGNÓSTICO MOLECULAR, PROVÍNCIA DE BUENOS AIRES, ARGENTINA

The detection of SARS-CoV-2 and its implication in the diagnosis of COVID-19 have been highly debated in the pandemic. Access to molecular diagnosis and its target population was essential in the public policy. The objective of this study was to evaluate the cost / benefit of detecting SARS-CoV-2 in asymptomatic close contacts using different molecular diagnostic tests. 51 close contacts of people with a diagnosis of SARS-CoV-2 confirmed by RTqPCR, classified by Ct (<20, between 20 and 30 and> 30), were studied in public hospitals in Province of Buenos Aires. Of all contacts studied, 15.7% were confirmed for SARS-CoV-2, there were no contacts of cases with Ct> 30 positive. The number of positive contacts of cases with Ct <20 was significantly higher than that of cases with Cts> 20. Samples with Cts <20 were associated with an estimated viral load of 1 to 4 orders of magnitude difference with Ct ranges> 20. 13.7% of positive close contacts were from cases with Ct <20. When studying positive samples with confirmed diagnosis by PCR, corresponding to EW1 of 2021, only 19.35% corresponded to samples with Cts <20 and 50.7% with Cts between 20 and 30. From these data it is shown that with the close contact test we could detect only 3.7% of cases. The effort by the public health system for this strategy, with low predictive power, may have a negative effect on the fulfillment of the isolation of contacts and could generate a delay in the results of suspected cases, without contributing significantly to controlling the pandemic.

La detección de SARS-CoV-2 y su implicancia en el diagnóstico de COVID-19 han sido muy debatidos en la pandemia. El acceso al diagnóstico molecular y su población destinataria fue parte esencial de las políticas públicas. El objetivo de este estudio fue evaluar el costo/beneficio de la detección de SARS-CoV-2 en contactos estrechos asintomáticos mediante el uso de distintas pruebas de diagnóstico molecular. Se estudiaron 51 contactos estrechos de personas con diagnóstico de SARS-CoV-2 confirmado por RTqPCR, clasificadas por Ct (<20, entre 20 y 30 y >30) en hospitales públicos de la Provincia de Buenos Aires. Del total de contactos estudiados el 15,7% resultó confirmado para SARS-CoV-2, no hubo contactos de casos con Ct>30 positivos. La cantidad de contactos positivos de casos con Ct<20 fue significativamente mayor que la de casos con Cts>20. Las muestras con Cts<20 se asociaron a una carga viral estimada de entre 1 a 4 órdenes de magnitud de diferencia con los rangos de Ct >20. Un 13,7% de contactos estrechos positivos fueron de casos con Ct<20. Al estudiar muestras positivas con diagnóstico confirmado por PCR, correspondientes a la SE1 del 2021, sólo un 19,35% correspondían a muestras con Cts<20 y un 50,7% con Cts entre 20 y 30. A partir de estos datos se muestra que con el testeo de contactos estrechos podríamos detectar sólo un 3,7% de casos. El esfuerzo por parte del sistema de salud pública para esta estrategia, con bajo poder predictivo, puede tener un efecto negativo para el cumplimiento del aislamiento de los contactos y podría generar una demora en los resultados de los casos sospechosos, sin aportar significativamente a controlar la pandemia.

A detecção de SARS-CoV-2 e sua implicação no diagnóstico de COVID-19 têm sido altamente debatidos na pandemia. O acesso ao diagnóstico molecular e à sua população-alvo era parte essencial das políticas públicas. O objetivo deste estudo foi avaliar o custo / benefício da detecção da SARS-CoV-2 em contatos próximos assintomáticos usando diferentes testes de diagnóstico molecular. 51 contatos próximos de pessoas com diagnóstico de SARS-CoV-2 confirmado pelo RTqPCR, classificados pelo Ct (<20, entre 20 e 30 e> 30), foram estudados em hospitais públicos da Província de Buenos Aires. Do total de contatos estudados, 15,7% foram confirmados para SARS-CoV-2, não houve contato de casos com Ct> 30 positivo. O número de contatos positivos de casos com Ct <20 foi significativamente maior que o de casos com Ct> 20. As amostras com Cts <20 foram associadas a uma carga viral estimada de 1 a 4 ordens de diferença de magnitude com intervalos de Ct> 20. 13,7% dos contatos próximos positivos eram de casos com Ct <20. Ao estudar amostras positivas com diagnóstico confirmado por PCR, correspondentes a EW1 de 2021, apenas 19,35% corresponderam a amostras com Cts <20 e 50,7% com Cts entre 20 e 30. A partir desses dados, mostra-se que com o teste de contato próximo poderíamos detectar apenas 3,7% dos casos. O esforço do sistema público de saúde por essa estratégia, com baixo poder preditivo, pode repercutir negativamente no cumprimento do isolamento dos contatos e pode gerar atraso nos resultados dos casos suspeitos, sem contribuir significativamente para o controle da pandemia.

COVID-19 y vulnerabilidad social Análisis descriptivo de una serie de casos del gran Bueno Aires / COVID-19 and social vulnerability: descriptive study about a case series in Gran Buenos Aires

INTRODUCCIÓN: La morbimortalidad por la enfermedad por el nuevo coronavirus (COVID-19) constituye un problema de salud pública en la Provincia de Buenos Aires y en el resto de Argentina. Las poblaciones con vulnerabilidad social están expuestas a riesgos de manera potenciada. OBJETIVO: Describir la evolución de los casos confirmados de COVID-19 en el Gran Buenos Aires, localizados en zonas con diferentes características sociales categorizadas por vulnerabilidad socioterritorial, desde el inicio de la pandemia hasta el 15 de julio de 2020. MÉTODOS: Estudio descriptivo de corte transversal. Las variables analizadas fueron sexo, edad, evolución de la enfermedad y domicilio categorizado por medio del índice de vulnerabilidad socioterritorial (IVST). RESULTADOS: La mayor cantidad de casos positivos para COVID-19 se encontró en el grupo etario de 20 a 59 años, y el 48% fueron mujeres. El 47% de los casos estudiados residían en zonas vulnerables. El 28% de los casos confirmados requirieron internación. Se internaron en unidades de cuidados intensivos el 3,8% del total de los casos confirmados. Los casos de residentes en zonas no vulnerables tuvieron mayor requerimiento de cuidados intensivos. La letalidad fue de 3,5%, mayor en los varones, y más elevada en residentes de zonas no vulnerables, con una diferencia estadísticamente significativa respecto a los pertenecientes a zonas vulnerables. En la distribución por grupos etarios, se observó un exceso de letalidad estadísticamente significativo en menores de 60 años. DISCUSIÓN: Se observó un número mayor de internaciones en UCI y en la letalidad del grupo de población residente en territorio no vulnerable.

Impacto de vacunación de COVID-19 en las infecciones por SARS-COV-2 en personal de salud de la provincia de Buenos Aires / Impact of vaccines against COVID-19 on new SARS-COV2 infections in health care workers of the Province of Buenos Aires

INTRODUCCIÓN: La vacunación en la provincia de Buenos Aires inició con personal de salud (PS). El objetivo de este trabajo es evaluar el impacto de la vacunación sobre la evolución de los casos de infección por SARS-CoV-2 en el PS, comparado con la de la población general (PG). MÉTODOS: Estudio observacional descriptivo de series temporales de casos confirmados de COVID-19, entre abril de 2020 y marzo de 2021. Se utilizó el sistema de información VacunatePBA y el SNVS. Se tomó el grado de inmunización a 14 días de la aplicación de la vacuna. RESULTADOS: A partir de septiembre de 2020, el número de casos disminuyó en el PS, en comparación con la PG. Para fines de febrero de 2021 estaba inmunizado con primera dosis (PD) el 42% del PS y con segunda dosis (SD) el 24%, mientras que en PG solo estaba inmunizado el 0,06% con PD y nadie SD. En marzo de 2021 mientras la cantidad de casos en PG (con 2% inmunizada) aumentó un 10% con respecto a febrero, en PS disminuyó un 35% (95% de esa población inmunizada). Esto indica una disminución significativa entre los nuevos casos de febrero y de marzo en PS (p <0,00001). DISCUSIÓN: A partir del inicio de la vacunación contra COVID-19 a finales de diciembre 2020, se muestra una disminución de casos nuevos de COVID-19 en PS. Este trabajo describe una disminución relativa de los casos en PS luego de la vacunación en la provincia de Buenos Aires y aporta los primeros datos del país sobre el impacto de las vacunas contra COVID-19

Persistence of antibodies IgG to SARS-CoV2 in health care workers ­ Province of Buenos Aires / Persistencia de anticuerpos IgG contra SARS-CoV2 en personal de salud - provincia de Buenos Aires.

Aim: To evaluate the persistence of IgG antibodies to SARS-CoV2, in health workers of the public subsector of the Province of Buenos Aires, and correlate it with demographic variables (sex, age) and other health indicators (diagnosis of COVID-19, comorbidities and pregnancy). Methodology: Descriptive, observational, cross-sectional study. Health workers with a positive result in a first sample (N = 388) underwent a second test to evaluate the persistence of antibodies by ELISA. Results: Of the 386 people evaluated with a conclusive result, 296 had a first positive result between 30 and 90 days before the second test, of these, 90% had detectable antibodies. In those with a positive result more than 90 days ago (45), a significant decrease in persistence of 26.7% was observed. There were no significant associations between demographic and health variables and the second test result. Conclusion: Antibodies remain detectable for at least 90 days in 90% of the cases analyzed. It is main to continue this study over time to have a major period of time between tests. The information shown here throws interesting and promising data regarding the possible protection of new COVID-19 infections in personnel with high risk exposure. This evidence could contribute to decision-making, both at the local and regional level, for the adequate vaccination planning, as well as for the management in the event of a possible second wave scenario of COVID-19 pandemic in Latin America.

Objetivo: evaluar la persistencia de los anticuerpos IgG contra SARS-CoV2, en trabajadores de salud del subsector público de la Provincia de Buenos Aires, y correlacionarla con variables demográficas (sexo, edad) y otros indicadores de salud (diagnóstico de COVID-19, comorbilidades y embarazo). Metodología: Estudio descriptivo, observacional, de corte transversal. Al personal de salud con un resultado positivo en una primera muestra (N=388) se les realizó una segunda prueba para evaluar la persistencia de anticuerpos mediante ELISA. Resultados: De las 386 personas evaluadas con resultado concluyente, 296 contaban con un primer resultado positivo entre los 30 y los 90 días anteriores a la segunda prueba, el 90% presentó anticuerpos detectables. En aquellas personas con un resultado positivo hacía más de 90 días (45) se observó una caída significativa en la persistencia del 26,7%. No hubo asociaciones significativas entre las variables demográficas y de salud y el resultado de la segunda prueba. Conclusión: Los anticuerpos se mantienen detectables por al menos 90 días en el 90% de los casos analizados. Resulta fundamental continuar este estudio en el tiempo para contar con un período de tiempo mayor entre pruebas. La información aquí mostrada arroja datos interesantes y prometedores en cuanto a la posible protección de nuevos contagios de COVID-19 en personal con alta exposición de riesgo. Estas evidencias podrían contribuir a la toma de decisiones, tanto a nivel local como regional, para la adecuada planificación de la vacunación, así como también, para el manejo de la pandemia ante una posible segunda ola de casos en América Latina.

Seroprevalencia de infección por SARS-CoV-2 en personal de salud de la Región Sanitaria VIII, provincia de Buenos Aires, Argentina / Pandemic and social inequiality: the popular neighborhoods of the Buenos Aires suburbs in preventive social isolation

INTRODUCCIÓN en el contexto de pandemia por el nuevo coronavirus (COVID-19), la situación del personal de salud (PS) constituye un foco de interés, tanto por su alta exposición como por la posibilidad de convertirse en diseminadores de la infección en la comunidad. Estos trabajadores enfrentan un riesgo laboral de morbimortalidad sin precedentes. El objetivo fue estimar la seroprevalencia de infección por el nuevo coronavirus (SARS-CoV-2) en el PS de la Región Sanitaria VIII, provincia de Buenos Aires, durante junio de 2020. MÉTODOS se utilizó un diseño transversal. Se realizó un muestreo probabilístico por conglomerados bietápico. Se recabaron datos a partir de un cuestionario autoadministrado y una muestra de sangre para determinación de anticuerpos. Se utilizó el test COVIDAR IgG e IgM®. RESULTADOS se incluyeron 738 trabajadores de la salud, la tasa de respuesta general fue del 73,80 %. El 71,83% fueron mujeres, el 46,39% tenía entre 35 y 49 años. Enfermeros y médicos representaron más de la mitad del personal. El 75,86% refirió usar siempre el equipo de protección personal. El 5,61% tuvo contacto estrecho con un caso confirmado de COVID-19. El 4,60% tenía un hisopado nasofaríngeo previo, con resultado negativo. Se encontraron cinco trabajadores con IgG positiva para SARS-CoV-2 (cuatro mujeres y un varón) e IgM negativa. La edad media de los casos fue de 35 años, dos fueron asintomáticos, en ninguno se había tomado muestra de hisopado. La seroprevalencia general fue de 0,75%, sin diferencias significativas entre estratos. DISCUSIÓN la seroprevalencia hallada fue baja, con una gran proporción de trabajadores susceptibles a la infección. Se refuerza la necesidad de complementar las estrategias de vigilancia epidemiológica pasiva con el monitoreo serológico en personal de salud.

INTRODUCTION in the context of the new coronavirus (COVID-19) pandemic, the situation of health care workers (HCW) constitutes a focus of interest, due to their high exposure and the possibility of becoming disseminators of the infection in the community These workers face an unprecedented occupational risk of morbidity and mortality The aim of this study was to estimate the seroprevalence of the new coronavirus (SARS-CoV-2) infection in health workers of the Sanitary Region VIII, at province of Buenos Aires during June 2020. METHODS a cross-sectional design was used. A probabilistic sampling by two-stage conglomerates was carried out. Data were collected from a self-administered questionnaire and a blood sample for antibody identification. The COVIDAR IgG and IgM® test was used. RESULTS 738 health workers were included; the overall response rate was 73.80%. 71.83% of that were women; 46.39% were between 35 and 49 years of age. Nurses and physicians accounted for more than half of the staff. 75.86% of people claimed to always use personal protective equipment. 5.61% of people had close contact with a confirmed case of COVID-19.4.60% of people had previously had a nasopharyngeal swab with a negative result. Five workers had positive IgG for SARS-CoV-2 (four women and one man), with negative IgM. The mean age of the cases was 35 years old; two of them were asymptomatic; neither of them had a swab sample taken. The overall seroprevalence was 0.75%, with no significant differences between strata. DISCUSSION the seroprevalence found was low; indicating a large proportion of workers was susceptible to infection. We stress the need to complement passive epidemiological surveillance strategies with serological monitoring in health workers.

COVID-19 AND SOCIAL VULNERABILITY: DESCRIPTIVE STUDY ABOUT A CASE SERIE IN THE METROPOLITAN AREA OF BUENOS AIRES* / COVID-19 Y VULNERABILIDAD SOCIAL: ANALISIS DESCRIPTIVO DE UNA SERIE DE CASOS DEL AREA METROPOLITANA DE BUENOS AIRES*

Introduction: Morbidity and mortality due to COVID-19 constitutes a global public health problem, in Argentina and the Buenos Aires province. Populations with social vulnerability have a fragility which exposes them to grater risks.. Objective: To characterize the social vulnerability of a series of confirmed cases that reside in the Metropolitan Area of Buenos Aires. Methods: Descriptive cross-sectional study. Variables of gender, age, evolution and domicile were analyzed and categorized through the Socio-Territorial Vulnerability Index (STVI). Results: the age of the cases was between 20 and 59 years, 48% was female and the remaining male. 47% of the cases were from vulnerable areas. Hospitalizations were 28% of the cases, the majority from non-vulnerable areas. 3.8% of the cases reached intensive care. Vulnerable cases had a greater need for intensive care. The fatality rate was 2.4% and higher in men. After age 60, the fatality excess in vulnerable areas was statistically significant. Discussion: Among the cases, there were no important differences between residents of vulnerable and non-vulnerable areas. The differences were marked in severity (measured by ICU admission) and in the fatality rate of those over 60 years old, which was higher in vulnerable areas. Vulnerability was expressed in the evolution of the disease in those over 60 years of age.

Introducción: La morbi-mortalidad por COVID-19 constituye un problema de salud pública en Argentina y la Provincia de Buenos Aires. Las poblaciones con vulnerabilidad social poseen una fragilidad que las expone a riesgos de manera potenciada. Objetivo: Caracterizar la vulnerabilidad social de una serie de casos confirmados con residencia en el Área Metropolitana Buenos Aires. Métodos: Estudio descriptivo de corte transversal. Fueron analizadas variables de sexo, edad, evolución y domicilio categorizadas por medio del Índice de Vulnerabilidad Socio Territorial. Resultados: la edad de los casos fue entre 20 y 59 años, el sexo fue un 48% mujeres y el restante varones. De zonas vulnerables hubo un 47% de casos. Las internaciones fueron el 28% de los casos, la mayoría de zonas no vulnerables. Llegaron a cuidados intensivos el 3,8% de los casos. Los casos con vulnerabilidad tuvieron mayor requerimiento de cuidados intensivos.  La letalidad fue de 2,4% y fue mayor en varones. A partir de los 60 años el exceso de letalidad en zonas vulnerables fue estadísticamente significativo. Discusión: Entre los casos no hubo diferencias importantes entre los residentes de zonas vulnerables y no vulnerables. Las diferencias estuvieron marcadas en la gravedad (medido por internación en UCI) y letalidad de los mayores de 60 años que fue mayor en zonas vulnerables. La vulnerabilidad se expresó en la evolución de la enfermedad de los mayores de 60 años.

Introdução: A morbi mortalidade pela COVID-19 constitue um problema de saúde pública na Argentina e na provincia de Buenos Aires. A população com vulnerabilidade social possui uma fragilidade que expoe-as de maneira potenciada. Objetivos: Caraterizar a vulnerabilidade social de uma serie de casos confirmados com residencia na area metropolitana de Buenos Aires. Métodos: Estudo descritivo de corte transversal. Foram analisadas varaiveis de sexo, idade, evolução e domicilio categorizado por medio do índice de de Vulnerabilidade Socio territorial (IVST). Resultados: A idade dos casos foi entre 20 e 59 anos, o sexo femenino acumulou um 48% dos casos e o restante foram homens. Das zonas vulneraveis houve um 47% dos casos. As inernações foram o 28% dos casos, a maioria de casos não vulneráveis. Foram encaminhados para terapia intensiva o 3,8% dos casos. Os casos vulneraveis tiveram maior requerimento de cuidados intensivos. A letalidade foi de 2,4% e foi maior nos homens. A partir de 60 anos, o excesso da letalidade foi em casos com residência em zonas vulneráveis e isto foi estatisticamente significativo. Conclusões: Entre os casos não se acharam diferenças importantes com relaçáo à vulnerabilidade. As diferenças estiveram marcadas na gravidade dos casos onde os maiores de 60 anos requeriram maiores cuidados intensivos e foi mais elevada a letalidade. A vulnerabilidade expressou-se na evolução da doença.

Surveillance and Seroprevalence: Evaluation of IgG antibodies for SARS-Cov2 by ELISA in the popular neighborhood Villa Azul, Quilmes, province of Buenos Aires, Argentina / Vigilancia y Seroprevalencia: Evaluación de anticuerpos IgG para SARS-Cov2 mediante ELISA en el barrio popular Villa Azul, Quilmes, Provincia de Buenos Aires, Argentina / Vigilância e soroprevalência: Avaliação de anticorpos IgG para SARS-Cov2 por ELISA no Bairro vulnerável de Villa Azul, Quilmes, Província de Buenos Aires, Argentina

Objective: To evaluate the prevalence of antibodies against SARS Cov-2 in Barrio Villa Azul, in the Quilmes district, together with other demographic and mobility variables. Methods: Descriptive cross-sectional study carried out through a systematic probabilistic sample. The sample consisted of 311 cases, of which 284 cases consented to the application of the test. A survey was applied to 100% of the cases tested. The information was processed with SPSS 23 software and the analysis considered the weighting of the sample according to the established probabilistic design. Results: 61% were women. The mean age was 40 years, the population structure was similar to that of the universe. The presence of antibodies was 14.8% of the cases, the majority in women and 40 year-old who did not go to work and did not use public transport. Being a health worker did not represent a greater risk for infection. It is observed that of each symptomatic case there would be 1.2 asymptomatic. Conclusions: There was a higher prevalence of people with antibodies than in other studies, although comparing similar territories the prevalence of antibodies was lower and this could be a consequence of a timely territorial approach. The seroprevalence was predominantly in women and this would not indicate greater contagion in this sex since there is uncertainty in the relationship between infection and antibodies. It was observed that the infections could have been within the home or in the community environment since it affected people who did not go out to work.

Objetivo: Evaluar la prevalencia de anticuerpos para SARS Cov-2 en el Barrio Villa Azul, del partido de Quilmes, junto con otras variables demográficas y de movilidad. Métodos: Estudio descriptivo de corte transversal realizado a través de una muestra probabilística sistemática. El tamaño de la muestra fue de 311 casos y consintieron la aplicación del test 284 casos. Fue aplicada una encuesta al 100% de los casos testeados. La información fue procesada con software SPSS 23 y los análisis consideraron la ponderación de la muestra de acuerdo al diseño equiprobabilístico establecido. Resultados: El 61% eran mujeres. La media de edad era de 40 años, la estructura poblacional era similar a la del universo. La presencia de anticuerpos fue del 14,8% de los casos, la mayoría en mujeres y de 40 años que no salieron a trabajar y no utilizaron transporte público. El ser trabajador de la salud no representó un riesgo acrecentado para el contagio. Se observa que de cada un caso sintomático existirían 1,2 asintomáticos. Conclusiones: Hubo una prevalencia mayor de personas con anticuerpos que en otros estudios, aunque comparando territorios similares la prevalencia de anticuerpos fue menor y esto pude ser una consecuencia de un abordaje territorial oportuno. La seroprevalencia fue predominantemente en mujeres y esto no indicaría mayor contagio en este sexo ya que existe incertidumbre en la relación entre infección y anticuerpos. Se observó que los contagios podrían haber sido dentro del hogar o el entorno comunitario ya que afectó a personas que no salían a trabajar.

Objetivo: Avaliar a prevalência de anticorpos para SARS-cOV2 no bairro Villa Azul do Município de Quilmes na Argentina. Métodos: Estudo descritivo de corte transversal realizado a partir de uma amostra probabilística sistemática. O tamanho da amostra foi de 311 casos sendo que aceitaram a realização da prova 248 casos. Foi aplicado um formulário a todos os casos testados. A informação foi processada com o software SPSS 23 e as análises tomaram em conta a ponderação da amostra de acordo ao desenho probabilístico estabelecido. Resultados: O 61% eram mulheres. A média de idade foi de 40 anos, a estrutura populacional era similar à do universo de estudo. A presença de anticorpos foi no 14,8% dos casos, maioria mulheres, de 40 anos e que não saíram para o trabalho e a maioria não usaram o transporte público. O fato de ser trabalhador da saúde não acrescentou o risco do contagio. Observou-se que por cada caso sintomático houveram 1,2 casos assintomáticos. Conclusões: Houve uma prevalência maior de anticorpos do que em outros estudos. A soroprevalência foi maior em mulheres e isto não estaria indicando maior contagio em este sexo devido à incerteza entre a relação entre infeção e anticorpos. Observou-se que os contágios poderiam ter acontecido dentro do lar e no entorno comunitário já que afetou ás pessoas que não saiam para trabalhar

Seroprevalencia de infección por SARS-COV-2 en personal de salud de la region sanitaria VIII, provincia de Buenos Aires, Argentina / Seroprevalence of the SARS-CoV-2 infection in health workers of the Sanitary Region VIII, at province of Buenos Aires

INTRODUCCIÓN: en el contexto de pandemia por el nuevo coronavirus (COVID-19), la situación del personal de salud (PS) constituye un foco de interés, tanto por su alta exposición como por la posibilidad de convertirse en diseminadores de la infección en la comunidad. Estos trabajadores enfrentan un riesgo laboral de morbimortalidad sin precedentes. El objetivo fue estimar la seroprevalencia de infección por el nuevo coronavirus (SARS-CoV-2) en el PS de la Región Sanitaria VIII, provincia de Buenos Aires, durante junio de 2020. MÉTODOS: se utilizó un diseño transversal. Se realizó un muestreo probabilístico por conglomerados bietápico. Se recabaron datos a partir de un cuestionario autoadministrado y una muestra de sangre para determinación de anticuerpos. Se utilizó el test COVIDAR IgG e IgM®. RESULTADOS: se incluyeron 738 trabajadores de la salud, la tasa de respuesta general fue del 73,80 %. El 71,83% fueron mujeres, el 46,39% tenía entre 35 y 49 años. Enfermeros y médicos representaron más de la mitad del personal. El 75,86% refirió usar siempre el equipo de protección personal. El 5,61% tuvo contacto estrecho con un caso confirmado de COVID-19. El 4,60% tenía un hisopado nasofaríngeo previo, con resultado negativo. Se encontraron cinco trabajadores con IgG positiva para SARS-CoV-2 (cuatro mujeres y un varón) e IgM negativa. La edad media de los casos fue de 35 años, dos fueron asintomáticos, en ninguno se había tomado muestra de hisopado. La seroprevalencia general fue de 0,75%, sin diferencias significativas entre estratos. DISCUSIÓN: la seroprevalencia hallada fue baja, con una gran proporción de trabajadores susceptibles a la infección. Se refuerza la necesidad de complementar las estrategias de vigilancia epidemiológica pasiva con el monitoreo serológico en personal de salud

Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial.

Purpose The vasopressin analog desmopressin (dDAVP) is known to increase plasma levels of hemostatic factors, and preclinical studies in colorectal cancer models have demonstrated that it hampers tumor vascularization and metastatic progression. We evaluated safety and preliminary efficacy of dDAVP in rectal cancer patients with bleeding, before receiving specific oncologic treatment with surgery, chemotherapy and/or radiotherapy. Methods Patients with rectal cancer having moderate or severe rectal bleeding were enrolled in an open-label, dose-finding trial. Intravenous infusions of dDAVP were administered during two consecutive days in doses from 0.25 to 2.0 µg/kg, using single or twice daily regimen. Bleeding was graded using a score based on the Chutkan scale and tumor perfusion was evaluated by dynamic contrast-enhanced magnetic resonance imaging. Results The trial accrued a total of 32 patients. Dose-limiting toxicity occurred in patients receiving 1 µg/kg or higher. The most prominent treatment-related severe adverse event was hyponatremia. Most patients receiving the maximum tolerated dose of 0.5 µg/kg showed at least a partial hemostatic response and 58% developed a complete response with absence of bleeding at day 4 and/or at the last follow-up at day 14. Tumor perfusion was decreased in two-thirds of patients after dDAVP treatment. Conclusions dDAVP appeared as a promising hemostatic agent in rectal cancer patients with bleeding. Randomized clinical trials to confirm its effectiveness are warranted.Clinical trial registration www.clinicaltrials.gov NCT01623206.

Development and therapeutic potential of vasopressin synthetic analog [V4Q5]dDAVP as a novel anticancer agent.

Since its discovery, arginine vasopressin (AVP) was subjected to several modifications with the aim of obtaining novel derivatives with increased potency and selectivity for biomedical use. Desmopressin (dDAVP) is a first generation synthetic analog of AVP with hemostatic and antimetastatic activity. dDAVP acts as a selective agonist of the arginine vasopressin type 2 receptor (AVPR2) present in microvascular endothelium and cancer cells. Considering its selective effects on AVPR2-expressing malignant and vascular tissue, and interesting antitumor profile, dDAVP was used as a lead compound for the development of novel peptide analogs with enhanced anticancer efficacy. After conducting different structure-activity relationship studies to determine key aminoacidic positions for its antitumor activity against AVPR2-expressing malignant cells, dDAVP was rationally modified and a wide panel of synthetic analogs with different sequence and structural modifications was assessed. As a result of this structure-based drug derivatization novel AVP analog [V4Q5]dDAVP (1-deamino-4-valine-5-glutamine-8-d-arginine vasopressin) was selected as the most active candidate and further developed. [V4Q5]dDAVP was evaluated in highly aggressive and metastatic cancer preclinical models deploying enhanced cytostatic, antimetastatic and angiostatic effects in comparison to parental peptide dDAVP. In addition, novel compound demonstrated good tolerability as evaluated in several toxicological studies, and cooperative therapeutic effects after combination with standard-of-care chemotherapy. In summary, due to its ability to inhibit growth and tumor-associated angiogenesis, as well as impairing progression of metastatic disease, AVP analogs such as novel [V4Q5]dDAVP are promising compounds for further development as coadjuvant agents for the management of advance or recurrent cancers.

Expression of bladder cancer-associated glycans in murine tumor cell lines.

The characterization of murine cell lines is of great importance in order to identify preclinical models that could resemble human diseases. Aberrant glycosylation includes the loss, excessive or novel expression of glycans and the appearance of truncated structures. MB49 and MB49-I are currently the only two murine cell lines available for the development of preclinical bladder cancer models. The glycans Lewis X (LeX), Sialyl lewis X (SLeX) and Sialyl Tn (STn) have previously been associated with aggressiveness, dissemination and poor prognosis in human bladder cancer, additionally N-glycolyl GM3 (NGcGM3) is a neo-antigen expressed in many types of tumors; however, to the best of our knowledge, its expression has not previously been assessed in this type of cancer. Taking into account the relevance of glycans in tumor biology and considering that they can act as targets of therapies and biomarkers, the present study evaluated the expression of LeX, SLeX, STn and NGcGM3 in MB49 and MB49-I cells, in different growth conditions such as monolayer cultures, three-dimensional multicellular spheroids and mouse heterotopic and orthotopic tumors. The expression of LeX was not detected in either cell line, whereas SLeX was expressed in monolayers, spheroids and orthotopic tumors of both cell lines. STn was only identified in MB49 monolayers and spheroids. There are no reports concerning the expression of NGcGM3 in human or murine bladder cancer. In our hands, MB49 and MB49-I expressed this ganglioside in all the growth conditions evaluated. The assessment of its expression in cancer cell lines and patient tumors is of great importance, considering the relevance of this ganglioside in tumor biology. The data obtained by the present study demonstrates that glycan expression may be substantially altered depending on the growth conditions, highlighting the importance of the characterization of murine cancer models. To the best of our knowledge, the present study is the first to examine the expression of cancer-associated glycans, in the two murine cell lines available for the development of preclinical studies in bladder cancer.