Browsing by Author "Jara, Alejandro"
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Publication Effectiveness of an inactivated SARS-CoV-2 vaccine in children and adolescents: a large-scale observational study(2023) Jara, Alejandro; Undurraga, Eduardo; Flores, Juan; Zubizarreta, José; González, Cecilia; Pizarro, Alejandra; Ortuño, Duniel; Acevedo, Johanna; Leo, Katherinne; Paredes, Fabio; Bralic , Tomás; Vergara, Verónica; Leon, Francisco; Parot, Ignacio; Leighton, Paulina; Suárez, Pamela; Rios, Juan; García, Heriberto; Rafael Araos; Araos Bralic, Rafael IgnacioBackground: Policymakers urgently need evidence to adequately balance the costs and benefits of mass vaccination against COVID-19 across all age groups, including children and adolescents. In this study, we aim to assess the effectiveness of CoronaVac's primary series among children and adolescents in Chile. Methods: We used a large prospective national cohort of about two million children and adolescents 6-16 years to estimate the effectiveness of an inactivated SARS-CoV-2 vaccine (CoronaVac) in preventing laboratory-confirmed symptomatic SARS-CoV-2 infection (COVID-19), hospitalisation, and admission to an intensive care unit (ICU) associated with COVID-19. We compared the risk of individuals treated with a complete primary immunization schedule (two doses, 28 days apart) with the risk of unvaccinated individuals during the follow-up period. The study was conducted in Chile from June 27, 2021, to January 12, 2022, when the SARS-CoV-2 Delta variant was predominant but other variants of concern were co-circulating, including Omicron. We used inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over the unvaccinated status, accounting for time-varying vaccination exposure and adjusting for relevant demographic, socioeconomic, and clinical confounders. Findings: The estimated adjusted vaccine effectiveness for the inactivated SARS-CoV-2 vaccine in children aged 6-16 years was 74.5% (95% CI, 73.8-75.2), 91.0% (95% CI, 87.8-93.4), 93.8% (95% CI, 87.8-93.4) for the prevention of COVID-19, hospitalisation, and ICU admission, respectively. For the subgroup of children 6-11 years, the vaccine effectiveness was 75.8% (95% CI, 74.7-76.8) for the prevention of COVID-19 and 77.9% (95% CI, 61.5-87.3) for the prevention of hospitalisation. Interpretation: Our results suggest that a complete primary immunization schedule with the inactivated SARS-CoV-2 vaccine provides effective protection against severe COVID-19 disease for children 6-16 years. Funding: Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP)Item Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile(2021) Jara, Alejandro; Undurraga, Eduardo; González, Cecilia; Paredes, Fabio; Fontecilla, Tomás; Jara, Gonzalo; Pizarro, Alejandra; Acevedo, Johanna; Leo, Katherinne; Leon, Francisco; Sans, Carlos; Leighton, Paulina; Suárez, Pamela; García-Escorza, Heriberto; Araos, Rafael;BACKGROUND Mass vaccination campaigns to prevent coronavirus disease 2019 (Covid-19) are occurring in many countries; estimates of vaccine effectiveness are urgently needed to support decision making. A countrywide mass vaccination campaign with the use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) was conducted in Chile starting on February 2, 2021. METHODS We used a prospective national cohort, including participants 16 years of age or older who were affiliated with the public national health care system, to assess the effectiveness of the inactivated SARS-CoV-2 vaccine with regard to preventing Covid-19 and related hospitalization, admission to the intensive care unit (ICU), and death. We estimated hazard ratios using the extension of the Cox proportional-hazards model, accounting for time-varying vaccination status. We estimated the change in the hazard ratio associated with partial immunization (≥14 days after receipt of the first dose and before receipt of the second dose) and full immunization (≥14 days after receipt of the second dose). Vaccine effectiveness was estimated with adjustment for individual demographic and clinical characteristics. RESULTS The study was conducted from February 2 through May 1, 2021, and the cohort included approximately 10.2 million persons. Among persons who were fully immunized, the adjusted vaccine effectiveness was 65.9% (95% confidence interval [CI], 65.2 to 66.6) for the prevention of Covid-19 and 87.5% (95% CI, 86.7 to 88.2) for the prevention of hospitalization, 90.3% (95% CI, 89.1 to 91.4) for the prevention of ICU admission, and 86.3% (95% CI, 84.5 to 87.9) for the prevention of Covid-19–related death.Publication Effectiveness of CoronaVac in children 3–5 years of age during the SARS-CoV-2 Omicron outbreak in Chile(2022) Jara, Alejandro; Undurraga, Eduardo A.; Zubizarreta, José R.; González, Cecilia; Acevedo, Johanna; Pizarro, Alejandra; Vergara, Verónica; Soto-Marchant, Mario; Gilabert, Rosario; Flores, Juan Carlos; Suárez, Pamela; Leighton, Paulina; Eguiguren, Pablo; Ríos, Juan Carlos; Fernández, Jorge; García-Escorza, Heriberto; Araos, RafaelThe outbreak of the B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Omicron) has caused an unprecedented number of Coronavirus Disease 2019 (COVID-19) cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but, to date, the evidence is sparse. Leveraging a population-based cohort in Chile of 490,694 children aged 3–5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of Sinovac’s inactivated SARS-CoV-2 vaccine (CoronaVac). We used inverse probability-weighted survival regression models to estimate hazard ratios of symptomatic COVID-19, hospitalization and admission to an intensive care unit (ICU) for children with complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between 6 December 2021 and 26 February 2022, during the Omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95% confidence interval (CI), 36.5–39.9) against symptomatic COVID-19, 64.6% (95% CI, 49.6–75.2) against hospitalization and 69.0% (95% CI, 18.6–88.2) against ICU admission. The effectiveness against symptomatic COVID-19 was modest; however, protection against severe disease was high. These results support vaccination of children aged 3–5 years to prevent severe illness and associated complications and highlight the importance of maintaining layered protections against SARS-CoV-2 infection.Publication Effectiveness of homologous and heterologous booster doses for an inactivated SARS-CoV-2 vaccine: a large-scale prospective cohort study(2022) Jara, Alejandro; Undurraga, Eduardo A.; Zubizarreta, José R.; González, Cecilia; Pizarro, Alejandra; Acevedo, Johanna; Leo, Katherinne; Paredes, Favio; Bralic, Tomás; Vergara, Verónica; Mosso, Marcelo; León, Francisco; Parot, Ignacio; Leighton, Paulina; Suárez, Pamela; Ríos, Juan Carlos; García-Escorza, Heriberto; Araos, RafaelBackground: Vaccine protection against Covid-19 may be waning. Several countries have authorized or begun using a booster vaccine dose. Policymakers urgently need evidence of the effectiveness of additional vaccine doses against Covid-19 and its clinical spectrum for individuals with complete primary immunization schedules. Methods: We used a prospective national cohort of 11·2 million persons 16 years or older to assess the effectiveness of CoronaVac, AZD1222, or BNT162b2 vaccine boosters in individuals who completed their primary immunization schedule with CoronaVac compared to unvaccinated individuals. The study was conducted in Chile from February 2 through November 10, 2021. We used inverse probability-weighted survival regression models to estimate hazard ratios, accounting for time-varying vaccination status and adjusting for relevant demographic, socioeconomic, and clinical confounders. We estimated the change in the hazard associated with complete immunization (≥14 days after the booster). Findings: We found an adjusted vaccine effectiveness against symptomatic Covid-19 of 78·8% (95% confidence interval, CI, 76·8–80·6) for a three-dose schedule with CoronaVac, 96·5% (95% CI, 96·2–96·7) for BNT162b2 booster, and 93·2% (95% CI, 92·9–93·6) for the AZD1222 booster. The adjusted vaccine effectiveness against hospitalization, ICU admission, and Covid-19 related deaths was 86·3%, 92·2%, and 86·7% for a three-dose schedule with CoronaVac, 96·1%, 96·2%, and 96·8% for the BNT162b2 booster, and 97·7%, 98·9%, and 98·1% for the AZD1222 booster. Interpretation: Our results suggest that a homologous or heterologous booster shot for individuals with a complete primary vaccination schedule with CoronaVac provides a high level of protection against Covid-19, including severe disease and death. However, heterologous boosters showed higher vaccine effectiveness for all outcomes, providing additional support for using a mix and match approach. Funding Information: Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The research protocol was approved by the Comité Ético Científico Clínica Alemana Universidad del Desarrollo. The study was considered exempt from informed consent, no human health risks were identified. Research analysts belong to the Chilean Ministry of Health; our use of data follows Chilean law 19·628 on personal data protection.Publication Effectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile(2023) Jara, Alejandro; Cuadrado, Cristobal; Undurraga, Eduardo; García , Christian; Nájera, Manuel; Bertoglia, María; Vergara, Verónica; Fernández , Jorge; García, Heriberto; Araos Bralic, Rafael IgnacioIn light of the ongoing COVID-19 pandemic and the emergence of new SARS-CoV-2 variants, understanding the effectiveness of various booster vaccination regimens is pivotal. In Chile, using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluate the effectiveness against COVID-19-related intensive care unit (ICU) admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series followed by a homologous booster, and CoronaVac primary series followed by an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimate the vaccine effectiveness weekly from February 14 to August 15, 2022, by determining hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot is 88.2% (95%CI, 86.2-89.9) against ICU admissions and 90.5% (95%CI 89.4-91.4) against death. Vaccine effectiveness shows a mild decrease for all regimens and outcomes, probably linked to the introduction of BA.4 and BA.5 Omicron sub-lineages and the waning of immunity. Based on our findings, individuals might not need additional boosters for at least 6 months after receiving a second mRNA booster shot in this setting. A la luz de la actual pandemia de COVID-19 y la aparición de nuevas variantes del SARS-CoV-2, es fundamental comprender la eficacia de varios regímenes de vacunación de refuerzo. En Chile, utilizando una cohorte nacional prospectiva de 3,75 millones de personas de 20 años o más, evaluamos la efectividad contra las admisiones a unidades de cuidados intensivos (UCI) relacionadas con COVID-19 y la muerte de segundas dosis de refuerzo basadas en ARNm para cuatro dosis diferentes de tres dosis. regímenes: serie primaria BNT162b2 seguida de un refuerzo homólogo, y serie primaria CoronaVac seguida de un refuerzo de ARNm, un refuerzo homólogo y un refuerzo de ChAdOx-1. Estimamos la efectividad de la vacuna semanalmente del 14 de febrero al 15 de agosto de 2022, determinando los índices de riesgo de inmunización frente a no vacunación, teniendo en cuenta los factores de confusión relevantes. La eficacia global ajustada de una segunda inyección de refuerzo de ARNm es del 88,2% (IC del 95%, 86,2-89,9) frente a los ingresos en la UCI y del 90,5% (IC del 95%, 89,4-91,4) frente a la muerte. La eficacia de la vacuna muestra una leve disminución en todos los regímenes y resultados, probablemente relacionada con la introducción de los sublinajes Omicron BA.4 y BA.5 y la disminución de la inmunidad. Según nuestros hallazgos, es posible que las personas no necesiten refuerzos adicionales durante al menos 6 meses después de recibir una segunda inyección de refuerzo de ARNm en este entorno.Publication High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study(2023) Araos Bralic, Rafael Ignacio; Smith, Rachel; Styczynski, Ashley; Sánchez, Felipe; Acevedo, Johanna; Maureira, Lea; Paredes, Catalina; González, Maite; Rivas Jiménez, Lina María; Spencer, Maria; Peters, Anne Sophie; Khan, Ayesha; Sepulveda, Dino; Rojas, Loreto; Rioseco, María; Usedo, Pedro; Rojas, Pamela; Huidobro, Laura; Ferreccio, Catterina; Park, Benjamin; Undurraga, Eduardo; D'Agata, Erika; Jara, Alejandro; Munita, Jose M.Background: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. Methods: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. Results: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. Conclusions: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.Publication Neutralizing antibodies induced by homologous and heterologous boosters in CoronaVac vaccines in Chile(2023) Acevedo, Johanna; Acevedo, Mónica L.; Gaete-Argel, Aracelly; Araos, Rafael; González, Cecilia; Espinoza, Daniela; Rivas, Solange; Pizarro, Pablo; Jarpa, Stephan; Soto-Rifo, Ricardo; Jara, Alejandro; Valiente-Echeverría, FernandoObjectives:To determine the impact of a booster dose on the humoral response in individuals inoculated with a complete schedule of any SARS-CoV-2 vaccine, we evaluated the neutralizing antibody (NAb) titres of homologous or heterologous booster doses over a 90-days period in CoronaVac vaccinees from 3 centres in Santiago, Chile. Methods:Individuals previously inoculated with 2 doses of CoronaVac (N = 523) were recruited in the context of the REFUERZO clinical trial (NCT04992182) and received either placebo (N = 129), or a booster dose of CoronaVac (N = 134), BNT162b2 (N = 133), or ChAdOx1 (N = 127). Pseudovirus neutralizing antibody titres (pVNT) were determined at baseline (day 0) as well as at days 14, 30, 60, and 90 after booster dose administration. Results:Inoculating a booster dose increases the pVNTs titres at days 14 and 30 in all groups, (13.5- and 12.0-fold increase for the CoronaVac group; 247.0- and 212.3-fold increase for the BTN162b2 group; and 89.1- and 128.1-fold increase for ChAdOx1 at each time point, respectively) with a decline observed at days 60 and 90. However, although pVNTs remained significantly higher for the BTN162b2 and ChAdOx1 groups at days 60 and 90, NAb titres reached baseline levels in the CoronaVac group at 90 days after inoculation. Discussion: A single heterologous booster (BTN162b2 or ChAdOx1) in individuals who completed the CoronaVac primary series resulted in an important increase in NAb titres remaining significantly higher at least for 90 days. These data may directly impact middle- and low-income countries currently using CoronaVac as the main vaccination strategy.Publication Quantitative Susceptibility Mapping MRI in Deep-Brain Nuclei in First-Episode Psychosis(2023) García Saborit, Marisleydis; Jara, Alejandro; Muñoz, Néstor; Milovic, Carlos; Tepper, Angeles; Alliende, Luz María; Mena, Carlos; Iruretagoyena, Bárbara; Ramírez-Mahaluf, Juan Pablo; Díaz, Camila; Nachar, Ruben; Castañeda, Carmen Paz; González, Alfonso; Undurraga, Juan; Crossley, Nicolás; Tejos, CristianBackground: Psychosis is related to neurochemical changes in deep-brain nuclei, particularly suggesting dopamine dysfunctions. We used an magnetic resonance imaging-based technique called quantitative susceptibility mapping (QSM) to study these regions in psychosis. QSM quantifies magnetic susceptibility in the brain, which is associated with iron concentrations. Since iron is a cofactor in dopamine pathways and co-localizes with inhibitory neurons, differences in QSM could reflect changes in these processes. Methods: We scanned 83 patients with first-episode psychosis and 64 healthy subjects. We reassessed 22 patients and 21 control subjects after 3 months. Mean susceptibility was measured in 6 deep-brain nuclei. Using linear mixed models, we analyzed the effect of case-control differences, region, age, gender, volume, framewise displacement (FD), treatment duration, dose, laterality, session, and psychotic symptoms on QSM. Results: Patients showed a significant susceptibility reduction in the putamen and globus pallidus externa (GPe). Patients also showed a significant R2* reduction in GPe. Age, gender, FD, session, group, and region are significant predictor variables for QSM. Dose, treatment duration, and volume were not predictor variables of QSM. Conclusions: Reduction in QSM and R2* suggests a decreased iron concentration in the GPe of patients. Susceptibility reduction in putamen cannot be associated with iron changes. Since changes observed in putamen and GPe were not associated with symptoms, dose, and treatment duration, we hypothesize that susceptibility may be a trait marker rather than a state marker, but this must be verified with long-term studies.Item Tool for Estimating the Probability of Having COVID-19 With 1 or More Negative RT-PCR Results(2021) Jara, Alejandro; Undurraga, Eduardo; Araos, RafaelEarly case detection and isolation of infected individuals are critical to controlling coronavirus disease 2019 (COVID-19). Reverse transcription polymerase chain reaction (RT-PCR) is considered the gold standard for the diagnosis of severe acute respiratory syndrome coronavirus 2 infection, but false negatives do occur. We built a user-friendly online tool to estimate the probability of having COVID-19 with negative RT-PCR results and thus avoid preventable transmission.