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Endothelial cells express multiple receptors mediating estrogen responses; including the G protein-coupled estrogen receptor (GPER). Past studies on nitric oxide (NO) production elicited by estrogens raised the question whether 17-ß-estradiol (E2) and natural phytoestrogens activate equivalent mechanisms. We hypothesized that E2 and phytoestrogens elicit NO production via coupling to distinct intracellular pathways signalling. To this aim, perfusion of E2 and phytoestrogens to the precontracted rat mesentery bed examined vasorelaxation, while fluorescence microscopy on primary endothelial cells cultures quantified single cell NO production determined following 4-amino-5-methylamino-2',7'-difluoroescein diacetate (DAF) incubation. Daidzein (DAI) and genistein (GEN) induced rapid vasodilatation associated to NO production. Multiple estrogen receptor activity was inferred based on the reduction of DAF-NO signals; G-36 (GPER antagonist) reduced 75 % of all estrogen responses, while fulvestrant (selective nuclear receptor antagonist) reduced significantly more the phytoestrogens responses than E2. The joint application of both antagonists abolished the E2 response but not the phytoestrogen-induced DAF-NO signals. Wortmannin or LY-294002 (PI3K inhibitors), reduced by 90% the E2-evoked signal while altering significantly less the DAI-induced response. In contrast, H-89 (PKA inhibitor), elicited a 23% reduction of the E2-induced signal while blocking 80% of the DAI-induced response. Desmethylxestospongin-B (IP3 receptor antagonist), decreased to equal extent the E2 or the DAI-induced signal. Epidermal growth factor (EGF) induced NO production, cell treatment with AG-1478, an EGF receptor kinase inhibitor reduced 90% DAI-induced response while only 53% the E2-induced signals; highlighting GPER induced EGF receptor trans-modulation. Receptor functional selectivity may explain distinct signalling pathways mediated by E2 and phytoestrogens.
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Proteínas Quinasas Dependientes de AMP Cíclico , Receptores ErbB , Estradiol , Óxido Nítrico , Fosfatidilinositol 3-Quinasas , Fitoestrógenos , Transducción de Señal , Vasodilatación , Animales , Fitoestrógenos/farmacología , Estradiol/farmacología , Óxido Nítrico/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores ErbB/metabolismo , Masculino , Isoflavonas/farmacología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Genisteína/farmacología , Receptores de Estrógenos/metabolismo , Ratas WistarRESUMEN
BACKGROUND AND PURPOSE: ATP is highly accumulated in secretory vesicles and secreted upon exocytosis from neurons and endocrine cells. In adrenal chromaffin granules, intraluminal ATP reaches concentrations over 100 mM. However, how these large amounts of ATP contribute to exocytosis has not been investigated. EXPERIMENTAL APPROACH: Exocytotic events in bovine and mouse adrenal chromaffin cells were measured with single cell amperometry. Cytosolic Ca2+ measurements were carried out in Fluo-4 loaded cells. Submembrane Ca2+ was examined in PC12 cells transfected with a membrane-tethered Ca2+ indicator Lck-GCaMP3. ATP release was measured using the luciferin/luciferase assay. Knockdown of P2X7 receptors was induced with short interfering RNA (siRNA). Direct Ca2+ influx through this receptor was measured using a P2X7 receptor-GCamp6 construct. KEY RESULTS: ATP induced exocytosis in chromaffin cells, whereas the ectonucleotidase apyrase reduced the release events induced by the nicotinic agonist dimethylphenylpiperazinium (DMPP), high KCl, or ionomycin. The purinergic agonist BzATP also promoted a secretory response that was dependent on extracellular Ca2+. A740003, a P2X7 receptor antagonist, abolished secretory responses of these secretagogues. Exocytosis was also diminished in chromaffin cells when P2X7 receptors were silenced using siRNAs and in cells of P2X7 receptor knockout mice. In PC12 cells, DMPP induced ATP release, triggering Ca2+ influx through P2X7 receptors. Furthermore, BzATP, DMPP, and KCl allowed the formation of submembrane Ca2+ microdomains inhibited by A740003. CONCLUSION AND IMPLICATIONS: Autocrine activation of P2X7 receptors constitutes a crucial feedback system that amplifies the secretion of catecholamines in chromaffin cells by favouring submembrane Ca2+ microdomains.
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Adenosina Trifosfato , Catecolaminas , Células Cromafines , Exocitosis , Receptores Purinérgicos P2X7 , Animales , Receptores Purinérgicos P2X7/metabolismo , Células Cromafines/metabolismo , Células Cromafines/efectos de los fármacos , Bovinos , Adenosina Trifosfato/metabolismo , Ratones , Catecolaminas/metabolismo , Exocitosis/efectos de los fármacos , Células PC12 , Ratas , Calcio/metabolismo , Comunicación Autocrina , Ratones Endogámicos C57BL , Células Cultivadas , MasculinoRESUMEN
Background: As the COVID-19 pandemic persists, infections continue to surge globally. Presently, the most effective strategies to curb the disease and prevent outbreaks involve fostering immunity, promptly identifying positive cases, and ensuring their timely isolation. Notably, there are instances where the SARS-CoV-2 virus remains infectious even after patients have completed their quarantine. Objective: Understanding viral persistence post-quarantine is crucial as it could account for localized infection outbreaks. Therefore, studying and documenting such instances is vital for shaping future public health policies. Design: This study delves into a unique case of SARS-CoV-2 persistence in a 60-year-old female healthcare worker with a medical history of hypertension and hypothyroidism. The research spans 55 days, marking the duration between her initial and subsequent diagnosis during Chile's first COVID-19 wave, with the analysis conducted using RT-qPCR. Results: Genomic sequencing-based phylogenetic analysis revealed that the SARS-CoV-2 detected in both Nasopharyngeal swab samples (NPSs) was consistent with the 20B clade of the Nextstrain classification, even after a 55-day interval. Conclusion: This research underscores the need for heightened vigilance concerning cases of viral persistence. Such instances, albeit rare, might be pivotal in understanding sporadic infection outbreaks that occur post-quarantine.
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The P2X7 receptor, a member of the P2X purinergic receptor family, is a non-selective ion channel. Over the years, it has been associated with various biological functions, from modulating to regulating inflammation. However, its emerging role in antigen presentation has captured the scientific community's attention. This function is essential for the immune system to identify and respond to external threats, such as pathogens and tumor cells, through T lymphocytes. New studies show that the P2X7 receptor is crucial for controlling how antigens are presented and how T cells are activated. These studies focus on antigen-presenting cells, like dendritic cells and macrophages. This review examines how the P2X7 receptor interferes with effective antigen presentation and activates T cells and discusses the fundamental mechanisms that can affect the immune response. Understanding these P2X7-mediated processes in great detail opens up exciting opportunities to create new immunological therapies.
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Presentación de Antígeno , Receptores Purinérgicos P2X7 , Activación de Linfocitos , Macrófagos , Células DendríticasRESUMEN
Introduction: As the SARS-CoV-2 continues to evolve, new variants pose a significant threat by potentially overriding the immunity conferred by vaccination and natural infection. This scenario can lead to an upswing in reinfections, amplified baseline epidemic activity, and localized outbreaks. In various global regions, estimates of breakthrough cases associated with the currently circulating viral variants, such as Omicron, have been reported. Nonetheless, specific data on the reinfection rate in Chile still needs to be included. Methods: Our study has focused on estimating COVID-19 reinfections per wave based on a sample of 578,670 RT-qPCR tests conducted at the University of Santiago of Chile (USACH) from April 2020 to July 2022, encompassing 345,997 individuals. Results: The analysis reveals that the highest rate of reinfections transpired during the fourth and fifth COVID-19 waves, primarily driven by the Omicron variant. These findings hold despite 80% of the Chilean population receiving complete vaccination under the primary scheme and 60% receiving at least one booster dose. On average, the interval between initial infection and reinfection was found to be 372 days. Interestingly, reinfection incidence was higher in women aged between 30 and 55. Additionally, the viral load during the second infection episode was lower, likely attributed to Chile's high vaccination rate. Discussion: This study demonstrates that the Omicron variant is behind Chile's highest number of reinfection cases, underscoring its potential for immune evasion. This vital epidemiological information contributes to developing and implementing effective public health policies.
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COVID-19 , SARS-CoV-2 , Humanos , Femenino , Adulto , Persona de Mediana Edad , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiología , Chile/epidemiología , Reinfección/epidemiologíaRESUMEN
Objective: To identify and describe innovative initiatives implemented as a response to the interruption of health services during the COVID-19 pandemic in Latin America and the Caribbean (LAC). Methods: This was a descriptive study that reviewed 34 initiatives implemented during the COVID-19 pandemic in LAC to address health services needs among deprioritized groups. The review of initiatives included four phases: a call for submissions of innovative initiatives from LAC countries; a selection of initiatives that had the ability to address health services gaps and that were innovative and effective; systematization and cataloging of the selected initiatives; and a content analysis of the information collected. Data were analyzed from September to October 2021. Results: The 34 initiatives show important variations regarding the target populations, the stakeholders involved, level of implementation, strategies, scope, and relevance of the innovative initiative. There was also evidence of the emergence of a bottom-up set of actions in the absence of top-down actions. Conclusion: The findings of this descriptive review of 34 initiatives implemented during the COVID-19 pandemic in LAC suggest that systematizing the strategies and lessons learned has the potential to expand learning for re-establishing and improving post-pandemic health services.
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ABSTRACT Objective. To identify and describe innovative initiatives implemented as a response to the interruption of health services during the COVID-19 pandemic in Latin America and the Caribbean (LAC). Methods. This was a descriptive study that reviewed 34 initiatives implemented during the COVID-19 pandemic in LAC to address health services needs among deprioritized groups. The review of initiatives included four phases: a call for submissions of innovative initiatives from LAC countries; a selection of initiatives that had the ability to address health services gaps and that were innovative and effective; systematization and cataloging of the selected initiatives; and a content analysis of the information collected. Data were analyzed from September to October 2021. Results. The 34 initiatives show important variations regarding the target populations, the stakeholders involved, level of implementation, strategies, scope, and relevance of the innovative initiative. There was also evidence of the emergence of a bottom-up set of actions in the absence of top-down actions. Conclusion. The findings of this descriptive review of 34 initiatives implemented during the COVID-19 pandemic in LAC suggest that systematizing the strategies and lessons learned has the potential to expand learning for re-establishing and improving post-pandemic health services.
RESUMEN Objetivo. Detectar y describir iniciativas innovadoras instrumentadas como respuesta a la interrupción de los servicios de salud durante la pandemia de COVID-19 en América Latina y el Caribe (ALC). Métodos. Se trata de un estudio descriptivo en el que se examinaron 34 iniciativas instrumentadas durante la pandemia de COVID-19 en ALC para hacer frente a las necesidades de servicios de salud en grupos poblacionales desatendidos. La revisión constó de cuatro fases: convocatoria para la presentación de iniciativas innovadoras por parte de los países de la Región; selección de iniciativas capaces de abordar las deficiencias en los servicios de salud y que fueran innovadoras y eficaces; sistematización y clasificación de las iniciativas seleccionadas; y análisis del contenido de la información recopilada. Los datos se analizaron entre septiembre y octubre del 2021. Resultados. Las 34 iniciativas presentan importantes diferencias en cuanto a los grupos poblacionales destinatarios, las partes interesadas implicadas, el grado de aplicación, las estrategias, el alcance y la pertinencia de la iniciativa innovadora. También se constató el surgimiento de un conjunto de acciones generadas desde la base como respuesta a la ausencia de medidas aplicadas de forma descendente. Conclusión. Los resultados de esta revisión descriptiva de 34 iniciativas aplicadas en ALC durante la pandemia de COVID-19 sugieren que la sistematización de las estrategias y las enseñanzas extraídas podría ser útil para ampliar el aprendizaje con vistas al restablecimiento y la mejora de los servicios de salud pospandémicos.
RESUMO Objetivo. Identificar e descrever iniciativas inovadoras implementadas em resposta à interrupção dos serviços de saúde durante a pandemia de COVID-19 na América Latina e no Caribe (ALC). Métodos. Este estudo descritivo analisou 34 iniciativas implementadas durante a pandemia de COVID-19 na ALC para atender às necessidades de serviços de saúde entre grupos que haviam perdido prioridade. A análise das iniciativas incluiu quatro fases: chamada pública para a apresentação de iniciativas inovadoras de países da ALC; seleção de iniciativas inovadoras e efetivas capazes de abordar lacunas nos serviços de saúde; sistematização e catalogação das iniciativas selecionadas; e análise de conteúdo das informações coletadas. Os dados foram analisados de setembro a outubro de 2021. Resultados. As 34 iniciativas apresentam variações importantes com relação às populações-alvo, partes interessadas envolvidas, nível de implementação, estratégias, escopo e relevância da iniciativa inovadora. Também houve evidências do surgimento de um conjunto de ações de baixo para cima (bottom-up) na ausência de ações de cima para baixo (top-down). Conclusão. Os resultados desta análise descritiva de 34 iniciativas implementadas durante a pandemia de COVID-19 nos países da ALC sugerem que a sistematização das estratégias e das lições aprendidas tem o potencial de ampliar as oportunidades de aprendizado para reestabelecer e aprimorar os serviços de saúde pós-pandemia.
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Introduction: The COVID-19 pandemic is still in force, causing global public health challenges and threats. Although vaccination and herd immunity have proven to be the most efficient way to control the pandemic, massive and early testing of patients using the RT-qPCR technique is crucial for constant genomic surveillance. The appearance of variants of SARS-CoV-2 with new mutations can reduce the efficiency of diagnostic detection. In this sense, several commercial RT-qPCR kits have been the target of extensive analysis because low assay performance could lead to false-negative diagnoses. Methods: In this study, we evaluated the performance of three commercial RT-qPCR kits; Thermo Fisher (TaqMan 2019-nCoV Assay Kit v1), BGI and Roche (LightCycler® Multiplex RNA Virus Master) used for the diagnosis of COVID-19 throughout the pandemic in Santiago de Chile. Results: Under our best assay conditions, we found significant differences in Cq amplification values for control and viral probes, against the same nasopharyngeal swab samples (NPSs). In addition, in some cases, the sensitivity of the RT-qPCR kits decreased against viral variants. Conclusion: Our study suggests evaluating the RT-qPCR kits used to detect SARS-CoV-2 because variants such as Omicron, which has several mutations, can compromise their detection and underestimate viral circulation.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Pandemias , COVID-19/diagnóstico , Chile , Nasofaringe , ARN Viral/genética , ARN Viral/análisis , Sensibilidad y EspecificidadRESUMEN
The COVID-19 pandemic continues to affect several countries. One of the best ways to control its spread is the timely identification of infected patients for isolation and quarantine. While an episode of infection lasts an average of 8-10 days from the onset of symptoms, there is literature describing long-lasting viral persistence events. Here, we report a case of persistence of SARS-CoV-2 for 386 days in a health worker from Santiago de Chile. Our study could be one of the longest reported viral persistence events. RNA sequencing analyses indicated that the first positive diagnosis (8 June 2020) corresponded to a SARS-CoV-2 variant belonging to Clade Nextstrain 20A. Three hundred eighty-six days later (23 September 2021), the second positive result reached the same viral variant (Clade 20A) but without presence or circulation in Chile since May 2021. Both sequencing coverages showed an identity of 99.21%, with some mutations related to the severity of the disease (ORF1b:P314L) and more infectivity (S:D614G). This work reinforces the idea of implementing an RT-qPCR or rapid antigen test once the quarantine is fulfilled to ensure viral absence, identify potential persistence, and, consequently, minimize the risk of local outbreaks of SARS-CoV-2 infection.
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The COVID-19 pandemic continues to be a concern and keeps global health authorities on alert. The RT-PCR technique has been the gold-standard assay for detecting the SARS-CoV-2 virus. However, rapid antigen tests (RATs) have been widely used to increase the number of tests faster and more efficiently in the population. Nevertheless, the appearance of new viral variants, with genomic mutations associated with greater contagiousness and immune evasion, highlights the need to evaluate the sensitivity of these RATs. This report evaluates the sensitivity of SD Biosensor-Roche, Panbio™, and Clinitest® RATs widely used in Santiago de Chile in the detection of the Omicron variant from Nasopharyngeal samples (NPSs), the most predominant SARS-CoV-2 variant in Chile and the world. SD Biosensor-Roche shows a detection sensitivity of 95.7% in the viral amplification range of 20 ≤ Cq < 25, while Panbio™ and Clinitest® show 100% and 91.3%, respectively. In the viral amplification ranges of 25 ≤ Cq < 30, the detection sensitivity decreased to 28% for SD Biosensor-Roche, 32% for Panbio™, and 72% for Clinitest®. This study indicates that the tested RATs have high sensitivity in detecting the Omicron variant of concern (VOC) at high viral loads. By contrast, its sensitivity decreases at low viral loads. Therefore, it is suggested to limit the use of RATs as an active search method, considering that infections in patients are increasingly associated with lower viral loads of SARS-CoV-2. These antecedents could prevent contagion outbreaks and reduce the underestimation of the current Omicron variant circulation at the local level.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Pandemias , Chile , Sensibilidad y Especificidad , NasofaringeRESUMEN
The variant of concern (VOC) SARS-CoV-2 Omicron (B.1.1529) has been described as a highly contagious variant but less virulent than the current variant being monitored (VBM) Delta (B.1.617.2), causing fewer cases of hospitalizations, symptomatology, and deaths associated with COVID-19 disease. Although the epidemiological comparison of both variants has been previously reported in other countries, no report indicates their behavior and severity of infection in Chile. In this work, we report for the first time the effect of the Omicron and Delta variants in a cohort of 588 patients from the Hospital de Urgencia Asistencia pública (HUAP), a high-complexity health center in Santiago, Chile. This report is framed at the beginning of Chile's third wave of the COVID-19 pandemic, with a marked increase in the Omicron variant and a decrease in the circulating Delta variant. Our results indicated a similar proportion of patients with a complete vaccination schedule for both variants. However, the Delta variant was associated with a higher prevalence of hospitalization and more significant symptomatology associated with respiratory distress. On the other hand, our data suggest that vaccination is less effective in preventing infection by the Omicron variant. This antecedent, with a low severity but high contagiousness, suggests that the Omicron variant could even collapse the primary health care service due to the high demand for health care.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Chile/epidemiología , PandemiasRESUMEN
The early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the real-time quantitative polymerase chain reaction (RT-qPCR) as a gold-standard molecular tool has allowed to test and trace the viral spread and the isolation of COVID-19-infected patients. The detection capacity of viral and internal genes is an essential parameter to consider and analyze during the assay. In this study, we analyze the performance of the two commercial RT-qPCR kits used in Chile, TaqMan™ 2019-nCoV Control Kit v1 (Thermo Fisher) and MaxCov19 (TAAG Genetics), for the COVID-19 diagnosis from nasopharyngeal swab samples (NPSs). Our results show a lower sensitivity of the TAAG kit compared to the Thermo Fisher kit, even in the detection of SARS-CoV-2 mutations associated with its variants. This study reinforces the relevance of evaluating the performance of RT-qPCR kits before being used massively since those with lower sensitivity can generate false negatives and produce outbreaks of local infections.
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The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many countries have reported the experience of at least two contagion waves, describing associated mortality rates and population behavior. The analysis of the effect of this pandemic in different localities can provide valuable information on the key factors to consider in the face of future massive infectious diseases. This work describes the first retrospective and comparative study about behavior during the first and second waves of the COVID-19 pandemic in Chile from a primary Healthcare Center. From 19,313 real-time quantitative PCR (RT-qPCR) tests assessed, the selected 1,694 positive diagnostics showed a decrease in mortality rate in the second wave (0.6%) compared with the first (4.6%). In addition, we observed that infections in the second wave were mainly in young patients with reduced comorbidities. The population with a complete vaccination schedule shows a decrease in the duration of symptoms related to the disease, and patients with more comorbidities tend to develop severe illness. This report provides evidence to partially understand the behavior and critical factors in the severity of the COVID-19 pandemic in the population of Santiago of Chile.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Chile/epidemiología , Humanos , Estudios Longitudinales , Pandemias , Atención Primaria de Salud , Estudios RetrospectivosRESUMEN
The identification and tracking of SARS-CoV-2 infected patients in the general population are essential components of the global strategy to limit the COVID-19 viral spread, specifically for maintaining traceability and suppressing the resurgence of local outbreaks. Public health programs that include continuous RT-qPCR testing for COVID-19 in the general population, viral sequencing, and genomic surveillance for highly contagious forms of the virus have allowed for the identification of SARS-CoV-2 infections and reinfections. This work identified SARS-CoV-2 reinfection in a homeless person, which occurred 58 days after the first COVID-19 diagnosis. Genomic sequencing identified a different Nextstrain classification clade (20A and 20B) and PANGO lineage, with a divergence of 4 single nucleotide variants (SNVs) in S and ORF1ab genes, suggesting reinfection by different viral variants. This study is the first from the great metropolitan area of Santiago, Chile, one of the top ten countries in the world to live during the COVID-19 pandemic. We support the importance of performing intensive genomic surveillance programs in the whole population and high-risk groups, such as homeless people, nearly 20 thousand people in Chile, and have limited access to health care services and poor viral traceability.
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COVID-19 , Personas con Mala Vivienda , COVID-19/epidemiología , Prueba de COVID-19 , Chile/epidemiología , Humanos , Pandemias , Reinfección , SARS-CoV-2/genéticaRESUMEN
Personal protective measures such use of face masks, hand washing and physical distancing have proven to be effective in controlling the spread of the Covid-19 pandemic. However, adherence to these measures may have been relaxed over time. The objective of this work is to assess the change in adherence to these measures and to find factors that explain the change For this purpose, we conducted a survey in the Metropolitan Region of Chile in which we asked the adherence to these measures in August-September 2021 and retrospectively for 2020. With the answers obtained we fit a logistic regression model in which the response variable is the relaxation of each of the self-care preventive actions. The explanatory variables used are socio-demographic characteristics such as the age, sex, income, and vaccination status of the respondents. The results obtained show that there has been a significant decrease in adherence to the three personal protection measures in the Metropolitan Region of Chile. In addition, it was observed that younger people are more likely to relax these measures. The results show the importance of generating new incentives for maintaining adherence to personal protection measures.
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COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Chile/epidemiología , Estudios Transversales , Humanos , Pandemias/prevención & control , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Vaccine administration is one of the most efficient ways to control the current coronavirus disease 2019 (COVID-19) pandemic. However, the appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can avoid the immunity generated by vaccines. Thus, in patients with a complete vaccine schedule, the infection by SARS-CoV-2 may cause severe, mild, and asymptomatic manifestations of the disease. In this case report, we describe for the first time the clinical symptoms of four patients (three symptomatic; one asymptomatic) from Santiago of Chile, with a complete vaccination schedule with two doses of CoronaVac (Sinovac Life Science) infected with the variant of interest (VOI) B.1.621 (Mu). They were compared with four unvaccinated patients, who had a higher prevalence of symptoms after infection compared to vaccinated patients. In the CoronaVac-vaccinated group, an 80-year-old patient who registered various comorbidities required Invasive mechanical ventilation for 28 days with current home medical recovery discharge. By contrast, in the unvaccinated group, a 71-year-old presented more symptoms with more than 45 days of Invasive mechanical ventilation, which continues to date, presenting greater lung damage than the vaccinated hospitalized patient. This first report evidence differences in the clinical symptomatology of patients vaccinated and non-vaccinated infected with the VOI B.1.621 (Mu) and suggest the protective effects of CoronaVac against this variant.
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COVID-19 , Vacunas , Anciano , Anciano de 80 o más Años , Vacunas contra la COVID-19 , Chile , Humanos , SARS-CoV-2 , VacunaciónRESUMEN
INTRODUCTION: During the COVID-19 pandemic, limited access to health care augmented COVID-19 risk in subjects with opioid use disorder (OUD). The aim of the study was to compare COVID-19 incidence in individuals with OUD receiving continuous clinical care with that of the general population. METHODS: A prospective cohort study was carried out from March 2020 to March 2021 comparing COVID-19 cumulative incidence of individuals presenting an OUD receiving integrated clinical care with that of an age-reference general population, in three public outpatient treatment centers for addiction in Barcelona, Spain. RESULTS: Over the study period, 366 individuals received clinical care. Mean age: 48.2±8.9 years, 280 (76.5%) were men and 283 (77.3%) native Spanish. All subjects were on opioid agonist therapy. Prevalence of communicable diseases were: HIV infection in 109 (29.8%) and hepatitis C in 46 (12.6%). Psychiatric comorbidity was present in 207 (56.6%), and 119 (32.5%) had >1 chronic medical disease. COVID-19 WAS DIAGNOSED IN 10 PATIENTS: a cumulative incidence of 2,732 casesx100,000 people/year (C.I.95%: 1,318-4,967). There were no differences compared to the age-general population: 2,856 casesx100,000 people/year (C.I.95%: 2,830-2,880) (p=0.81). In the bivariate analysis, hypertension (5[50.0%] vs. 53[14.9%], p=0.01) and cardiovascular chronic diseases (2 [20.0%] vs. 8 [2.2%], p=0.03) were more prevalent in patients with OUD and COVID-19. CONCLUSIONS: Individuals with OUD who received integrated clinical care had a COVID-19 incidence comparable to the general population. Ensuring comprehensive healthcare is essential to prevent the clinical impact of COVID-19 on individuals with OUD.
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Due to the COVID-19 pandemic, many transport kits have been manufactured to preserve and transport nasopharyngeal swab samples (NPSs) from patients. However, there is no information on the performance of the different virus transport media (VTM) used in COVID-19 diagnosis in the population of Santiago de Chile. We compared the RT-qPCR amplification profile of five different viral transport kit mediums, including DNA/RNA Shield™, NAT, VTM-N, Ezmedlab™, and phosphate-buffered saline (PBS), for NPSs from Central Metropolitan Health Service, Santiago, Chile. The DNA/RNA Shield™ medium showed a better performance in terms of Cq and RFU values for the internal reference RNase P and viral ORF1ab probes. By contrast, the PBS transport medium registered higher Cq values for the viral and reference gene, compared to the other VTM. DNA/RNA Shield™ shows higher relative fluorescence units (RFUs) and lower Cq values for the reference gene. Collectively, our results suggest that the PBS medium could compromise the sample diagnosis because of its lower RT-qPCR performance. The NAT, Ezmedlab and VTM-N, and DNA/RNA Shield™ media show acceptable RT-qPCR parameters and, consequently, seem suitable for use in COVID-19 diagnosis.
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COVID-19 , COVID-19/diagnóstico , Prueba de COVID-19 , Chile , Medios de Cultivo , Humanos , Nasofaringe , Pandemias , ARN , ARN Viral/análisis , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , SARS-CoV-2/genética , Manejo de Especímenes/métodosRESUMEN
T cell activation requires the processing and presentation of antigenic peptides in the context of a major histocompatibility complex (MHC complex). Cross-dressing is a non-conventional antigen presentation mechanism, involving the transfer of preformed peptide/MHC complexes from whole cells, such as apoptotic cells (ACs) to the cell membrane of professional antigen-presenting cells (APCs), such as dendritic cells (DCs). This is an essential mechanism for the induction of immune response against viral antigens, tumors, and graft rejection, which until now has not been clarified. Here we show for first time that the P2X7 receptor (P2X7R) is crucial to induce cross-dressing between ACs and Bone-Marrow DCs (BMDCs). In controlled ex vivo assays, we found that the P2X7R in both ACs and BMDCs is required to induce membrane and fully functional peptide/MHC complex transfer to BMDCs. These findings show that acquisition of ACs-derived preformed antigen/MHC-I complexes by BMDCs requires P2X7R expression.
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OBJECTIVE: Describe the perceptions of key actors regarding the disruption of health services for populations that ceased to be prioritized because of the COVID-19 pandemic-pregnant women, newborn, children, adolescents, and women-in countries of Latin America and the Caribbean (LAC) during the first stage of the pandemic. METHODS: In this cross-sectional study, a 35-question survey was administered to key actors in 19 LAC countries between July and September 2020. The respondents were asked for their personal perceptions regarding the situation of social and health services in their country before and during the pandemic. They were also asked for a projection of the situation during the post-pandemic period. RESULTS: In the 691 responses received, the main perception was that coverage in the services analyzed had been high before the pandemic, although their quality was not as highly rated. Both the coverage and quality of services were thought to have declined for adolescents and women. The majority of respondents predicted that all services will continue to function at lower than usual coverage levels for another three months (53.1%) and another 12 months (41.3%). Guaranteeing coverage and access to health services was considered the main policy challenge going forward. The next most needed initiatives noted were financing for actions to support women, children, and adolescents, and protection against violence and promotion of measures to combat it. CONCLUSIONS: Although the pandemic has struck all countries, its effect on the delivery of services in the populations analyzed differs from country to country and according to the types of service. It is essential to invest in national information systems that will make it possible to monitor the different services and identify the populations that need to be prioritized.
OBJETIVOS: Descrever a percepção de atores-chave na interrupção dos serviços de saúde para populações não priorizadas na pandemia grávidas, recém-nascidos, crianças, adolescentes e mulheres em países da América Latina e do Caribe (ALC) durante a primeira fase da pandemia de COVID-19. MÉTODOS: Estudo transversal. Foi realizada uma pesquisa com atores relevantes de 19 países da ALC entre julho e setembro de 2020, com 35 perguntas sobre a percepção pessoal do estado dos serviços sociais e de saúde em seus países antes e durante a pandemia, bem como uma projeção para depois dela. RESULTADOS: Nas 691 respostas, predominou a percepção de que a cobertura dos serviços analisados era alta antes da pandemia, embora a qualidade fosse vista como mais baixa. Notou-se uma redução na cobertura e na qualidade dos serviços a adolescentes e mulheres. A maioria estimou que todos os serviços seguiriam com uma menor cobertura tanto em 3 como em 12 meses (53,1% e 41,3%, respectivamente). Garantir a cobertura e o acesso aos serviços de saúde é o principal desafio político para o futuro, seguido do financiamento de iniciativas para mulheres, crianças e adolescentes, e da proteção e promoção contra a violência. CONCLUSÕES: Embora a pandemia tenha afetado todos os países, o abalo na provisão de serviços para as populações analisadas é heterogêneo entre os países e os tipos de serviço. É preciso investir em sistemas de informação nacionais que permitam monitorar os distintos serviços e identificar as populações que não foram priorizadas.