Mortalidad en pacientes hospitalizados por COVID-19 durante la primera ola en una institución de tercer nivel de Neuquén / Mortality in Patients Hospitalized for COVID-19 during the First Wave in a Tertiary Care Institution in Neuquén

Introducción: En diciembre de 2019, se detectó un brote de enfermedad por un nuevo coronavirus que evolucionó en pandemia con severa morbilidad respiratoria y mortali- dad. Los sistemas sanitarios debieron enfrentar una cantidad inesperada de pacientes con insuficiencia respiratoria. En Argentina, las medidas de cuarentena y control sani - tario retrasaron el primer pico de la pandemia y ofrecieron tiempo para preparar el sis- tema de salud con infraestructura, personal y protocolos basados en la mejor evidencia disponible en el momento. En una institución de tercer nivel de Neuquén, Argentina, se desarrolló un protocolo de atención para enfrentar la pandemia adaptado con la evo- lución de la mejor evidencia y evaluaciones periódicas de la mortalidad hospitalaria. Métodos: Estudio de cohorte observacional para evaluar la evolución de pacientes con COVID-19 con los protocolos asistenciales por la mortalidad hospitalaria global y al día 28 en la Clínica Pasteur de Neuquén en 2020. Resultados: Este informe describe los 501 pacientes diagnosticados hasta el 31 de di- ciembre de 2020. La mortalidad general fue del 16,6% (83/501) y del 12,2% (61/501) al día 28 de admisión. En los 139 (27,7%) pacientes con ventilación mecánica, la mortali- dad general y a los 28 días fue de 37,4% (52/139) y 28,1% (38/139) fallecieron, respec- tivamente. Los factores de riesgo identificados fueron edad, comorbilidades y altos re- querimientos de oxígeno al ingreso. Conclusión: La mortalidad observada en los pacientes hospitalizados en nuestra insti- tución en la primera ola de la pandemia COVID-19 fue similar a los informes internacio- nales y menor que la publicada en Argentina para el mismo período.

Introduction: In December 2019, an outbreak of disease due to a new coronavirus was detected that evolved into a pandemic with severe respiratory morbidity and mortality. Health systems had to face an unexpected number of patients with respiratory failure. In Argentina, quarantine and health control measures delayed the first peak of the pan - demic and offered time to prepare the health system with infrastructure, personnel and protocols based on the best evidence available at the time. In a third level institution of Neuquén, Argentina, a care protocol was developed to confront the pandemic adapted by evolving best evidence and periodic evaluations of hospital mortality. Methods: Observational cohort study to evaluate the evolution of patients hospitalized for COVID-19 with care protocols in terms of overall hospital mortality and at day 28 at the Pasteur Clinic in Neuquén in 2020. Results: This report describes the 501 patients diagnosed until December 31, 2020. Mortality was 16.6% (83/501) and 12.2% (61/501) on day 28 of admission. Among the 139 (27.7%) patients with mechanical ventilation, overall mortality and at 28 days it was 37.4% (52/139) and 28.1% (38/139), respectively. The risk factors identified were age, comorbidities and high oxygen requirements on admission. Conclusion: The mortality observed in patients hospitalized in our institution during the first wave of COVID-19 pandemic was similar to international reports and lower than other publications in Argentina for the same period.

Patrón de neumonía organizativa en TC de tórax: prevalencia y asociación con resultados clínicos en una cohorte de pacientes con COVID-19 grave/crítico / Organizing Pneumonia Pattern on Chest CT: Prevalence and Association with Clinical Outcomes in a Cohort of Patients with Severe/Critical COVID-19

Introducción: La neumonía por COVID-19 puede presentarse con dos patrones radio-lógicos: daño alveolar difuso o neumonía organizativa. Estos patrones tienen diferente evolución y pronóstico en pacientes sin infección por COVID-19. Nuestro objetivo fue evaluar la prevalencia del patrón radiológico de neumonía organizativa y su asociación con los desenlaces clínicos.Métodos: Se realizó un estudio de cohorte retrospectivo que incluyó a pacientes adultos hospitalizados por COVID-19 grave/crítica a los que se les realizó una tomografía computarizada de tórax en los 21 días posteriores al diagnóstico. Los patrones radiológicos fueron revisados y clasificados por dos radiólogos expertos. Resultados: De los 80 pacientes incluidos, el 89% (n=71) presentaron un patrón compatible con neumonía organizativa. Los principales hallazgos radiológicos fueron la distribución multilobar (98,7%) y bilateral (97,6%) con opacidades en vidrio esmerilado (97,6%). El 44% (n=33) de los sujetos requirió ingreso en cuidados intensivos, de los cuales el 24% (n=19) recibió ventilación mecánica. La presencia de neumonía organizativa se asoció de forma independiente con una disminución de las probabilidades de ventilación mecánica o muerte (Odds ratio 0,14; intervalo de confianza del 95%: 0,02 - 0,96; valor de p 0,045) en un modelo multivariado que incluía la edad, el sexo, el IMC y la afectación pulmonar en la TC.Conclusiones: Un patrón radiológico de neumonía organizativa es altamente prevalen-te en pacientes con COVID-19 grave/crítico y se asocia con mejores resultados clínico

Introduction: COVID-19 pneumonia can present with two distinct radiologic patterns: diffuse alveolar damage or organizing pneumonia. These patterns have been linked to different outcomes in non-COVID-19 settings. We sought to assess the prevalence of organizing pneumonia radiologic pattern and its association with clinical outcomes. Methods: We performed a retrospective cohort study including adult patients hospita- lized for severe/critical COVID-19 who underwent chest computed tomography within 21 days of diagnosis. Radiologic patterns were reviewed and classified by two expert radiologists. Results: Among 80 patients included, 89% (n=71) presented a pattern consistent with organizing pneumonia. The main radiologic findings were multilobar (98.7%) and bilateral (97.6%) distribution with ground glass opacities (97.6%). Intensive care admission was required for 44% (n=33) of subjects, of which 24% (n=19) received mechanical ventilation. The presence of organizing pneumonia was independently associated with a decreased odds of mechanical ventilation or death (Odds ratio 0.14; 95% confidence interval 0.02 - 0.96; p value 0.045) in a multivariate model including age, gender, BMI and lung involvement on CT. Conclusion: A radiologic pattern of organizing pneumonia is highly prevalent in patients with severe/critical COVID-19 and is associated with improved clinical outcomes.

Factores pronósticos de mortalidad a 30 días en neumonía por SARS-CoV-2 / Prognostic Factors for 30-day Mortality in SARS-CoV-2 Pneumonia

Introducción: SARS-CoV-2 ha causado millones de muertes a nivel global desde su primer caso reportado en China. En Guatemala existen pocos estudios que describan los factores pronósticos. Nuestro objetivo fue determinar los factores asociados de mortalidad a 30 días en pacientes con neumonía (Nm) por SARS-CoV-2 y construir un modelo predictor. Material y Métodos: Estudio retrospectivo en 144 sujetos en el Hospital Roosevelt de marzo a diciembre 2020 con criterios de Nm por SARS-CoV-2. Se revisó el expediente médico para datos clínicos y de laboratorio desde ingreso hasta alta hospitalaria o muerte. Resultados: Se evaluaron 105 hombres y 39 mujeres con media de edad 53 años. El 47% tenía comorbilidades como diabetes mellitus 2 e hipertensión arterial sistémica. Promedio de días de hospitalización: 13. Cuadros leves a moderados de Síndrome de Distrés Respiratorio Agudo (SDRA): 92%. Se indicó ventilación mecánica invasiva (VMI) a 46 pacientes. La mortalidad general fue 35%. Factores asociados a mortalidad a 30 días: edad ≥50 años, inicio de síntomas ≥7 días, SDRA severo, radio NL >4,4, recibir VMI, alteración en LDH y procalcitonina. Nuestro modelo mostró que los mejores predictores de mortalidad eran alteración en procalcitonina (OR: 4,45), recibir VMI (OR: 112) y días de estancia hospitalaria (OR: 1,12) con precisión de 91,5% y área bajo la curva de 94,4%. Conclusiones: Los factores pronósticos de mortalidad en pacientes guatemaltecos con Nm por SARS-CoV-2 son múltiples e incluyen rasgos demográficos, clínicos y serológicos; identificarlos y contar con un modelo pronóstico ayudará a brindar atención médica de precisión.

Introduction: SARS-CoV-2 has caused millions of deaths globally since its first case was reported in China. In Guatemala, few studies describe prognostic factors. Our objective was to determine the factors associated with 30 day mortality in patients with Pneumonia (Nm) due to SARS-CoV-2 and to build a predictor model. Material and Methods: Retrospective study in 144 subjects at Roosevelt Hospital from March to December 2020 with Nm criteria for SARS-CoV-2. The medical record was rviewed, obtaining clinical and laboratory data from admission to hospital discharge or death. Results: 105 men and 39 women with an average age of 53 years were evaluated. 47% had comorbidities, with type 2 diabetes mellitus and systemic arterial hypertension being common. The average number of days of hospitalization was 13. 92% had mild to moderate acute respiratory distress syndrome (ARDS). Invasive mechanical ventila-tion (IMV) was indicated for 46 patients. Overall mortality was 35%. The factors asso-ciated with 30-day mortality were age ≥50 years, the onset of symptoms ≥7 days, severe ARDS, N/L ratio >4.4, receiving IMV, alterations in LDH, and procalcitonin. Our model showed that the best predictors of mortality were altered procalcitonin (OR: 4.45), receiving IMV (OR: 112), and days of hospital stay (OR: 1.12) with precision of 91.5% and area under the curve of 94.4%. Conclusions: The prognostic factors of mortality in Guatemalan patients with Nm due to SARS-CoV-2 are multiple and include demographic, clinical and serological features; identifying them and having a prognostic model will help provide precision medical care.

Respuesta inmunitaria al SARS-CoV-2 previa a la vacunación en personal de salud de Alto Paraná, Paraguay, un estudio seroepidemiológico / Immune response to SARS-CoV-2 prior to vaccination among healthcare workers from Alto Paraná, Paraguay, a seroepidemiological study

INTRODUCCIÓN: La comprensión del comportamiento de la respuesta humoral en COVID-19 continúa siendo un desafío para la producción de vacunas que proporcionen inmunidad más duradera. OBJETIVO: Describir la respuesta humoral natural inducida por SARS- CoV-2 en personal de salud con base en el perfil epidemiológico y clínico. MATERIALES Y MÉTODOS: Estudio transversal en personal de salud de hospitales públicos de referencia del Departamento de Alto Paraná, Paraguay. Se incluyeron 962 participantes, mediante muestreo no probabilístico de tipo consecutivo, aplicación de cuestionario y toma de muestras sanguíneas. Se buscaron anticuerpos por ensayo inmunocromatográfico para detección de IgM e IgG contra SARS- CoV-2 y por el método ELISA de captura de IgG específicos contra la proteína spike (SARS-CoV-2) y se evaluaron factores asociados a la seropositividad. RESULTADOS: La seroprevalencia global fue 36,5% (IC 95%: 33,4 - 39,5); 59,3% (n: 571) de los encuestados refirió haber tenido síntomas compatibles al COVID-19 entre el inicio de la pandemia y la fecha de toma de muestra, de estos 44% (n: 251) resultó seropositivo; 10,4% (n: 100) manifestó no haber tenido síntomas en el periodo estudiado, pero tuvo un resultado positivo. Los factores asociados a la seropositividad fueron: presencia de síntomas (p 90 días). CONCLUSIONES: Las características clínicas fueron mayormente asociadas con la seropositividad y la seropreva- lencia en los sintomáticos varió de acuerdo con el tiempo transcurrido desde el inicio de los síntomas y la serología.

BACKGROUND: Understanding the behavior of humoral response in COVID-19 continues to be a challenge to produce vaccines that provide long-lasting immunity. AIM: To describe the natural humoral response induced by SARS-CoV-2 among healthcare workers based on epidemiological and clinical profiles. METHODS: Cross-sectional study in healthcare workers from public hospitals in the Department of Alto Paraná, Paraguay, 962 participants were recruited through consecutive sampling, using a questionnaire and blood sampling. Antibodies were determined by immunochromatography assay for detection of IgM and IgG and by SARS-CoV-2 IgG anti-spike capture ELISA method and factors associated with seropositivity were evaluated. RESULTS: The overall seropositivity was 36.5% (95% CI: 33.4 - 39.5); 59.3% (n: 571) of respondents reported symptoms compatible with COVID-19 since the start of the pandemic and the date of blood draw, 44% (n: 251) of them tested positive; 10.4% (n: 100) who reported no history of symptoms tested positive. The factors associated with seropositivity were the presence of symptoms (p 90 days). CONCLUSIONS: Clinical characteristics were mostly associated with seropositivity and sero prevalence in symptomatic participants varied according to the time elapsed from the onset of symptoms to serology.

Impacto de la pandemia por SARS-CoV-2 en el índice de masa corporal de niños asistidos en la Ciudad Autónoma de Buenos Aires / Impact of the SARS-CoV-2 pandemic on the body mass index of children seen in the City of Buenos Aires

Introducción. El sobrepeso y la obesidad infantil constituyen un problema de salud pública. El inicio de la pandemia por COVID-19 pudo haber favorecido esta patología. El puntaje Z del índice de masa corporal (Z-IMC) es un indicador aceptado para su diagnóstico y seguimiento. Objetivo. Evaluar si la prevalencia de sobrepeso y obesidad, y el Z-IMC en niños de 2 a 5 años aumentó durante la pandemia. Población y métodos. Estudio de cohorte retrospectiva. Se incluyeron pacientes asistidos en efectores públicos de salud del Gobierno de la Ciudad Autónoma de Buenos Aires (GCABA), de 2 a 5 años de edad, con registro de peso y talla en dos consultas, antes y después de haber comenzado el aislamiento social preventivo y obligatorio (ASPO). Se registró estado nutricional (Z-IMC) y variación del Z-IMC entre ambas consultas. Resultados. Se evaluaron 3866 sujetos, edad promedio 3,4 ± 0,8 años; el 48,1 % fueron mujeres. El intervalo promedio entre consultas fue 14,3 ± 2,5 meses. La prevalencia de sobrepeso/obesidad aumentó del 12,6 % (IC95% 11,6-13,6) al 20,9 % (IC95% 19,6-22-2); p <0,001, al igual que el Z-IMC (0,4 ± 1,1 vs. 0,8 ± 1,3; p <0,001). Conclusión. La prevalencia de sobrepeso y obesidad, y el Z-IMC en niños de 2 a 5 años aumentó significativamente durante la pandemia.

Introduction. Childhood overweight and obesity are a public health problem. The onset of the COVID-19 pandemic may have contributed to this condition. The body mass index (BMI) Z-score has been accepted as an indicator for overweight and obesity diagnosis and follow-up. Objective. To assess whether the prevalence of overweight and obesity and the BMI Z-score in children aged 2 to 5 years increased during the pandemic. Population and methods. Retrospective, cohort study. Patients included were those seen at public health care facilities in the City of Buenos Aires (CABA), who were aged 2 to 5 years, had weight and height values recorded at 2 different visits, before and after the establishment of the preventive and mandatory social isolation policy. Patients' nutritional status (BMI Z-score) and the variation in this indicator between both visits were recorded. Results. A total of 3866 subjects were assessed; their average age was 3.4 ± 0.8 years; 48.1% were girls. The average interval between both visits was 14.3 ± 2.5 months. The prevalence of overweight/ obesity increased from 12.6% (95% CI: 11.6­13.6) to 20.9% (95% CI: 19.6­22.2), p < 0.001, and so did the BMI Z-score (0.4 ± 1.1 versus 0.8 ± 1.3, p < 0.001). Conclusion. The prevalence of overweight and obesity and the BMI Z-score in children aged 2 to 5 years increased significantly during the pandemic.

Impacto de la edad, las comorbilidades y las complicaciones en pacientes con COVID-19 con síndrome de dificultad respiratoria aguda en la ventilación mecánica invasiva. Estudio multicéntrico observacional / Impact of Age, Comorbidities and Complications in COVID-19 Patients with Acute Respiratory Distress Syndrome on Invasive Mechanical Ventilation. An Observational Multicenter Study

Objetivos: Millones de pacientes con COVID-19 fueron internados en terapia intensiva en el mundo, la mitad desarrollaron síndrome de dificultad respiratoria aguda (SDRA) y recibieron ventilación mecánica invasiva (VMI), con una mortalidad del 50%. Analiza-mos cómo edad, comorbilidades y complicaciones, en pacientes con COVID-19 y SDRA que recibieron VMI, se asociaron con el riesgo de morir durante su hospitalización.Métodos: Estudio de cohorte observacional, retrospectivo y multicéntrico realizado en 5 hospitales (tres privados y dos públicos universitarios) de Argentina y Chile, durante el segundo semestre de 2020.Se incluyeron pacientes >18 años con infección por SARS-CoV-2 confirmada RT-PCR, que desarrollaron SDRA y fueron asistidos con VMI durante >48 horas, durante el se-gundo semestre de 2020. Se analizaron los antecedentes, las comorbilidades más fre-cuentes (obesidad, diabetes e hipertensión), y las complicaciones shock, insuficiencia renal aguda (IRA) y neumonía asociada a la ventilación mecánica (NAV), por un lado, y las alteraciones de parámetros clínicos y de laboratorio registrados.Resultados: El 69% era varón. La incidencia de comorbilidades difirió para los diferentes grupos de edad. La mortalidad aumentó significativamente con la edad (p<0,00001). Las comorbilidades, hipertensión y diabetes, y las complicaciones de IRA y shock se asociaron significativamente con la mortalidad. En el análisis multivariado, sólo la edad mayor de 60 años, la IRA y el shock permanecieron asociados con la mortalidad. Conclusiones: El SDRA en COVID-19 es más común entre los mayores. Solo la edad >60 años, el shock y la IRA se asociaron a la mortalidad en el análisis multivariado.

Objectives: Millions of patients with COVID-19 were admitted to intensive care world-wide, half developed acute respiratory distress syndrome (ARDS) and received invasive mechanical ventilation (IMV), with a mortality of 50%. We analyzed how age, comor-bidities and complications in patients with COVID-19 and ARDS who received IMV were associated with the risk of dying during their hospitalization.Methods: Observational, retrospective and multicenter cohort study carried out in 5 hospitals (three private and two public university hospitals) in Argentina and Chile, during the second half of 2020.Patients >18 years of age with SARS-CoV-2 infection confirmed by RT-PCR, who devel-oped ARDS and were assisted with IMV for >48 hours, during the second half of 2020, were included. History, the most frequent comorbidities (obesity, diabetes and hyper-tension) and the complications of shock, acute renal failure (AKI) and pneumonia as-sociated with mechanical ventilation (VAP), on the one hand, and the alterations of re-corded clinical and laboratory parameters, were analyzed.Results: 69% were men. The incidence of comorbidities differed for different age groups. Mortality increased significantly with age (p<0.00001). Comorbidities, hyper-tension and diabetes, and complications of ARF and shock were significantly associat-ed with mortality. In the multivariate analysis, only age over 60 years, ARF and shock remained associated with mortality.Conclusions: ARDS in COVID-19 is more common among the elderly. Only age >60 years, shock and ARF were associated with mortality in the multivariate analysis

Descripción de las intervenciones broncoscópicas en estenosis traqueales posterior a infección por COVID-19 / Description of Bronchoscopic Interventions in Post-COVID Tracheal Stenosis

Introducción: La infección por SARS-CoV-2 puede presentar síndrome de distrés res-piratorio agudo con requerimiento de ventilación mecánica prolongada y retraso en la realización de traqueostomía. Esto trae como consecuencia un incremento en casos de estenosis traqueal y la necesidad de métodos menos invasivos para su abordaje. Métodos: Estudio descriptivo de corte transversal, desde marzo 2020 hasta diciem-bre 2021 en el Hospital Universitario Nacional de Colombia, en adultos con estenosis traqueal postintubación asociado SARS-CoV-2. Se realizó análisis univariado entre los grupos con infección o no por SARS-CoV-2 como control, y reintervención, grado de estenosis, uso de inyección intramucosa con dexametasona intratraqueal o múltiples estenosis como desenlaces de importancia. Se usó test exacto de Fisher, t Student y Man-Whitney según la naturaleza de variables. Se consideró p estadísticamente significativo menor a 0.05.Resultados: Se identificaron 26 pacientes, 20 tenían COVID-19 y 6 no. Se encontraron diferencias en edad (p=0,002), epilepsia (p=0,007) y estenosis múltiple (p= 0,04). En 85% de los casos se utilizó láser blue más dilatación con balón pulmonar, en 35% inyección intramucosa con dexametasona intratraqueal y reintervención en 35%, sin diferencias significativas entre grupos. Conclusiones: Se observó un incremento tres veces mayor de pacientes con estenosis múltiple en el grupo de infección por COVID-19, así mismo se encontró que el método más utilizado en este grupo para la recanalización fue el uso de láser blue más dilatación con balón pulmonar y la innovación en el uso de inyección intramucosa.

Introduction: SARS-CoV-2 infection can lead to acute respiratory distress syndrome with a prolonged need for mechanical ventilation and delayed tracheostomy, resulting in an increase in cases of tracheal stenosis and the necessity for less invasive approaches.Methods: A descriptive cross-sectional study was conducted from March 2020 to December 2021 at the Hospital Universitario Nacional de Colombia, focusing on adults with post-intubation tracheal stenosis associated with SARS-CoV-2. Univariate analysis was performed between groups with or without SARS-CoV-2 infection as a control, considering reintervention, degree of stenosis, use of intratracheal steroids, or multiple stenoses as important outcomes. Fisher's exact test, Student's t-test, and Mann-Whit-ney test were employed based on the nature of variables. A p-value less than 0.05 was considered statistically significant.Results: A total of 26 patients were included, with 20 having COVID-19 and 6 without. Significant differences were found in age (p=0.002), epilepsy (p=0.007), and multiple stenosis (p=0.04). In 85% of cases, laser blue plus balloon pulmonary dilation was used, intratracheal dexamethasone in 35%, and reintervention in 35%, with no significant differences between groups.Conclusions: A threefold increase in subglottic stenosis was observed during the SARS-CoV-2 pandemic, with more instances of multiple stenosis and predominantly the use of laser blue plus balloon pulmonary dilation as a successful recanalization technique. There was a higher use of intratracheal dexamethasone in this group compared to oth-er pathologies causing tracheal stenosis.

Exceso de mortalidad durante la pandemia de COVID-19 en Ecuador. Análisis espacio temporal del exceso de mortalidad durante la pandemia de COVID-19 en Ecuador / Excess Mortality during the COVID- 19 Pandemic in Ecuador. Spatiotemporal Analysis of Excess Mortality During the Covid-19 Pandemic in Ecuador

Introducción: La pandemia de COVID-19 causó una elevada mortalidad en el mundo y en el Ecuador. Esta investigación se propuso analizar el exceso de mortalidad debido a la pandemia de COVID-19 en Ecuador. Método: Estudio observacional, longitudinal, cuantitativo y descriptivo. Clasificado como estudio ecológico en el campo de la epidemiología. Este estudio se centra en la medición del exceso de mortalidad durante los años 2020, 2021 y 2022, tomando como período base el promedio de defunciones ocurridas en el intervalo de 2015 a 2019. Resultados: Ecuador, en el período de enero 2020 a octubre 2022, acumuló un exceso total de muertes de 98.915. En el año 2020, el exceso de mortalidad fue mayor a 46.374, siendo el mes de abril el valor más alto de 15.484. En el año 2021, el exceso de muertes fue de 35.859, siendo abril el mes con mayor exceso de 7.330. Y el año 2022 el exceso de mortalidad fue de 16.682, el mes con mayor exceso fue enero con 4.204. Conclusión: Se evidenció un subregistro de defunciones, así como variaciones temporales y geográficas en el exceso de mortalidad. La provincia con mayor número de fallecidos y exceso de mortalidad fue Guayas seguida de Pichincha. Los resultados proporcionan un análisis del panorama durante la emergencia sanitaria, destacando la importancia de evaluar la capacidad de respuesta de los sistemas de salud en momentos de crisis y la necesidad imperativa de implementar medidas correctivas para el futuro.

Introduction: The COVID-19 pandemic caused a significant mortality in the world and in Ecuador. This research aimed to analyze the excess mortality due to the COVID-19 pandemic in Ecuador. Method: An observational, longitudinal, quantitative and descriptive study, classified as an ecological study in the field of epidemiology. This study focuses on measuring excess mortality during the years 2020, 2021 and 2022, using the average number of deaths that occurred in the period from 2015 to 2019 as the baseline. Results: From January 2020 to October 2022, Ecuador accumulated a total excess of deaths of 98,915. In 2020, the excess mortality was higher at 46,374, with the highest value occurring in April at 15,484. In 2021, the excess deaths amounted to 35,859, with April having the highest excess of 7,330. In 2022, the excess mortality was 16,682, with January recording the highest excess at 4,204. Conclusion: Evidence of underreporting of deaths, as well as temporal and geographi-cal variations in excess mortality, was observed. The province with the highest number of deaths and excess mortality was Guayas, followed by Pichincha. The results provide an analysis of the situation during the health emergency, emphasizing the importance of evaluating the healthcare system's capacity to respond during times of crisis and the imperative need to implement corrective measures for the future.

Reavaliação do nirmatrelvir/ritonavir para o tratamento de pacientes com COVID-19 não hospitalizados e com alto risco de doença grave / Revalidation of nirmatrelvir/ritonavir for the treatment of patients with COVID-19 who are not hospitalized and with a high risk of serious illness

INTRODUÇÃO: Pacientes com fatores de risco como idade avançada, imunodepressão, obesidade e doenças cardiovasculares têm risco aumentado de internação, intubação e morte. De acordo com dados brasileiros, o risco de morte por covid-19 aumenta com o número de fatores de risco que o paciente apresenta, sendo igual a 17% em pacientes com 2 fatores de risco e 76% na presença de 8 fatores de risco. Além disso, mesmo aqueles pacientes que sobrevivem a uma internação em terapia intensiva frequentemente enfrentam sequelas e representam alto custo para o sistema público. O medicamento nirmatrelvir associado ao ritonavir têm o objetivo de prevenir internações, complicações e morte. Ele é indicado para pacientes com Covid-19 leve a moderada, não hospitalizados, até 5 dias do início dos sintomas. Apesar dos avanços da vacinação no Brasil, evidências sobre a falha vacinal em idosos e imunodeprimidos destacam a importância da disponibilidade de alternativas terapêuticas para essas populações. O presente relatório teve por objetivo avaliar evidências sobre a efetividade do tratamento em pacientes vacinados com alto risco de agravamento da doença. PERGUNTA: O medicamento nirmatrelvir/ritonavir é eficaz, seguro e custo-efetivo para pacientes com covid19 leve a moderada não hospitalizados vacinados que apresentam alto risco de agravamento da doença? EVIDÊNCIAS CLÍNICAS: Resultados obtidos a partir de estudos observacionais de mundo real confirmaram os resultados do ensaio clínico do medicamento nirmatrelvir/ritonavir, demonstrando que o tratamento de pacientes de grupos de risco é capaz de reduzir o risco de desfechos desfavoráveis como internação e óbito entre cerca de 50% e 70%, inclusive entre pacientes previamente vacinados. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: A análise de impacto orçamentário do relatório de recomendação do nirmatrelvir/ritonavir foi atualizada considerando-se o cenário atual da pandemia no Brasil. De acordo com a nova análise, o uso do nirmatrelvir/ritonavir por pacientes com idade ≥ 65 anos e imunossuprimidos com idade ≥ 18 anos, resultaria em uma economia de recursos de R$ 408.957.111,38 em 5 anos. Ressalta-se, no entanto, que devido à dinâmica de difícil previsão da pandemia, este montante está sujeito à incerteza. Considerando-se a análise realizada anteriormente no relatório de recomendação, pode-se concluir que o montante economizado se reduz proporcionalmente à redução do número de casos da doença na população alvo. CONSIDERAÇÕES FINAIS: De acordo com as evidências atualmente disponíveis, o uso do nirmatrelvir/ritonavir é efetivo e seguro para pacientes com covid-19 leve a moderada não hospitalizados vacinados que apresentam alto risco de agravamento da doença. O impacto orçamentário está sujeito a incertezas já que o número de casos da doença no horizonte temporal da análise é de difícil previsão. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Diante do exposto, os membros do Comitê de Medicamentos da Conitec, em sua 16ª Reunião Extraordinária, realizada no dia 1º de novembro de 2023, deliberaram que a matéria fosse disponibilizada em Consulta Pública com recomendação preliminar favorável à incorporação no SUS do nirmatrelvir/ritonavir para o tratamento de pacientes com Covid-19 não hospitalizados com idade a partir de 65 anos ou pacientes imunossuprimidos a partir de 18 anos de idade. Os membros do Comitê concordaram na manutenção da indicação de uso, não havendo ampliação do público-alvo, justificada pela restrição orçamentária, considerando que há incremento de custo da aquisição da tecnologia, ainda que haja economia de recursos ao serem evitadas internações e óbitos. CONSULTA PÚBLICA: Das nove contribuições recebidas, cinco contribuições foram de cunho técnico-científico e quatro contribuições de experiência ou opinião. Todas as contribuições concordaram com a recomendação preliminar da Conitec de incorporar o nirmatrelvir/ritonavir. Duas contribuições técnico-científicassugeriram ampliação da população elegível ao tratamento com o medicamento com a inclusão de indicação para pacientes com taxa de filtração glomerular menor que 30 ml/min/1,73m2 e de pacientes adultos com asma grave independentemente da faixa etária. Uma contribuição técnico-científica enviada pela empresa fabricante do medicamento expressou sua concordância com e solicitou a inclusão de informaçõea adicionais no relatório. As contribuições de experiência ou opinião ressaltaram a eficácia e segurança do medicamento para a população alvo. RECOMEDAÇÃO FINAL DA CONITEC: Diante do exposto, os membros do Comitê de Medicamentos, presentes na 126ª Reunião Ordinária da Conitec, realizada no dia 01 de fevereiro de 2024, deliberaram, por unanimidade, após reavaliação, manter a incorporação do nirmatrelvir/ritonavir, no SUS, para o tratamento da Covid-19 nos seguintes grupos de pacientes com sintomas leves a moderados, que não requerem oxigênio suplementar, independentemente do status vacinal: a) imunocomprometidos com idade ≥ 18 anos; b) com idade ≥ 65 anos. Foi assinado o registro de deliberação nº 874/2024. DECISÃO: manter a incorporação, no âmbito do Sistema Único de Saúde - SUS, de nirmatrelvir/ritonavir para o tratamento da Covid-19 para pacientes com sintomas leves a moderados, que não requerem oxigênio suplementar, independentemente do status vacinal e com idade igual ou superior a 65 anos ou imunocomprometidos com idade igual ou superior a 18 anos, publicada no Diário Oficial da União nº 46, seção 1, página 54, em 07 de março de 2024.

Famotidina en el tratamiento de pacientes hospitalizados con COVID-19. Revisión sistemática y metaanálisis / Famotidine in the treatment of hospitalized patients with COVID-19. Systematic review and meta-analysis

Introducción: El síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2), de alta morbimortalidad, carece a la fecha de preparar esta revisión, de una terapia específica altamente eficaz. Famotidina se ha postulado como una opción terapéutica viable, basado en trabajos de cohorte retrospectiva y modelos computacionales guiados por inteligencia artificial. Objetivo: Recopilar la mejor evidencia científica disponible para determinar la efectividad y eficacia de famotidina en el tratamiento de pacientes hospitalizados con COVID-19, para reducir el riesgo de progresión de la enfermedad, intubación, muerte y tiempo de estancia hospitalaria. Material y Métodos: Se realizó una búsqueda en PubMed, EBSCO, Scopus, Web of Science y Cochrane Central, de artículos originales que reporten las variables de interés asociadas al uso de famotidina en pacientes hospitalizados con COVID- 19. Los investigadores independientemente evaluaron y seleccionaron los estudios, se extrajeron los datos expuestos para las asociaciones de interés y se procesaron con el software Revman 5.3. Resultados: En la búsqueda se obtuvo un total de 126 artículos potenciales para la revisión, de los cuales 14 fueron seleccionados para el análisis. En el metaanálisis se incluyeron un total de 47.044 pacientes, de los cuales 6.647 fueron los usuarios de famotidina. El riesgo de intubación se vio reducido en el grupo no expuesto a famotidina, aunque sin significancia estadística, (RR 1,43 IC95% 0,42-4,83), en cuanto a la mortalidad no se evidenció reducción significativa en el grupo de famotidina (RR 0,95 IC 95% 0,70-1,29). Se observó reducción en el tiempo de estancia hospitalaria (DM -1,60 -2,89, -0,31) y finalmente se mostró que no hay presencia de asociación entre el uso de famotidina y el desenlace compuesto de reducción del riesgo de ingreso a UCI, intubación y muerte (RR 1,03 IC 95% 0,46-2,34). Conclusión: Famotidina no presenta efectividad ni eficacia en la reducción de riesgo de intubación o ingreso a UCI ni de mortalidad en pacientes hospitalizados por COVID-19. La eficacia en la reducción de la estancia hospitalaria no es consistente y se necesitan más ensayos clínicos con buena calidad metodológica para definirla.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with high morbidity and mortality, lacks, at the time of preparing this review, a highly effective specific therapy. Famotidine has been postulated as a viable therapeutic option, based on retrospective cohort investigations and computational models guided by artificial intelligence. Aim: The objective of this study was to compile the best scientific evidence available to determine the effectiveness and efficacy of famotidine in the treatment of hospitalized patients with COVID-19, to reduce the risk of disease progression, intubation, death, and time to hospital stay. Methods: A search was carried out in PubMed, EBSCO, Scopus, Web of Science, and Central Cochrane, for original articles that report the variables of interest associated with the use of famotidine in hospitalized patients with COVID-19. The investigators independently evaluated and selected the studies, the exposed data for the associations of interest were extracted and processed with Revman 5.3 software. Results: The search yielded a total of 126 potential articles for the review, of which 14 were selected for analysis. A total of 47,044 patients were included in the meta-analysis of which 6,647 were famotidine users. The risk of intubation was reduced in the group not exposed to famotidine, although without statistical significance (RR 1.43 IC95% 0.42 - 4.83), regarding mortality there was no significant reduction in the famotidine group (RR 0.95 IC 95 % 0.70-1.29). A reduction in the length of hospital stay was observed (MD -1.60 -2.89, -0.31) and finally it was shown that there is no association between the use of famotidine and the composite outcome of reduced risk of ICU admission, intubation and death. (RR 1.03 95% CI 0.46-2.34). Conclusion: Famotidine does not show effectiveness or efficacy in reducing the risk of intubation or ICU admission or mortality in patients hospitalized for COVID-19. The efficacy in reducing hospital stay is not consistent and more clinical trials with good methodological quality are needed to define it.

Produção de anticorpos e citocinas em resposta ao SARS-CoV-2: comparação entre imunidade vacinal e híbrida / Antibody and cytokine production in response to SARS-CoV-2: vaccine versus hybrid immunity comparison

A resposta imunológica pelo SARS-CoV-2 após protocolos vacinais e infecção natural é pouco compreendida. Comparando indivíduos vacinados com esquema heterólogo que receberam um reforço vacinal (imunidade vacinal) com aqueles que apresentaram episódio leve de COVID-19 (imunidade híbrida) no mesmo período, verificamos níveis semelhantes de anticorpos contra SARS-CoV-2. Em culturas de células mononucleares, o estímulo com o antígeno viral induziu produção de citocinas pró-inflamatórias nos dois grupos, entretanto, os níveis de IL-17 foram menores em indivíduos com imunidade vacinal. Nossos resultados sugerem que o reforço vacinal teve efeitos semelhantes à infecção natural pelo SARS-CoV-2 na resposta imunológica de indivíduos previamente vacinados. (AU)

The immune response generated by SARS-CoV-2 vaccination protocols and natural infection remains incompletely understood. We compared individuals who received a heterologous vaccination scheme with a booster shot (vaccine immunity) to those who experienced a mild COVID-19 episode (hybrid immunity) during the same timeframe. Our findings revealed similar levels of SARS-CoV-2 antibodies in both groups. Stimulation by viral antigen in mononuclear cell cultures induced pro-inflammatory cytokines in both groups, while individuals with vaccine immunity exhibited lower IL-17. These results suggest that a vaccine booster can induce an immune response in previously vaccinated individuals comparable to that elicited by natural SARS-CoV-2 infection. (AU)

Corneal transplantation and concomitant SARS-CoV-2 infection: a case report / Transplante de córnea e infecção concomitante por SARS-CoV-2: relato de caso

ABSTRACT This report was aimed at presenting a case of neurotrophic keratitis and concomitant SARS-CoV-2 infection in a patient who has recently undergone a corneal DALK transplant. One month after corneal transplantation with adequate corneal epithelialization, the patient presented neurotrophic keratitis with a torpid course of the corneal transplant coinciding with a SARS-CoV-2 infection, with an excessive host immune response. In addition, the patient presented a re-positivization of nasopharyngeal polymerase chain reaction of SARS-CoV-2 with past disease after starting treatment with autologous serum eye drops. The implications at the ophthalmological level of SARS-CoV-2 infection may be clarified as the time the illness progresses and we learn more about how it acts. In this case, the disparity of signs and symptoms, the antecedent of corneal surgery, and the possibility of a herpetic infection as a cause of the primary leukoma suggested neurotrophic keratitis. Nonetheless, the involvement of systemic SARS-CoV-2 infection in the process, triggering an excessive host immune response at the corneal level with an increase in inflammatory cytokines must be taken into account. No relationship was found between treatment with autologous serum and re-positivization of nasopharyngeal polymerase chain reaction, presenting the patient a favorable response to treatment.

RESUMO O objetivo deste relato foi apresentar um caso de ceratite neurotrófica e infecção concomitante por SARS-CoV-2 em paciente submetido recentemente a transplante de córnea DALK. Um mês após o transplante de córnea com adequada epitelização da córnea, o paciente apresentou ceratite neurotrófica com curso tórpido do transplante de córnea, coincidindo com infecção por SARS-CoV-2, com resposta imune excessiva do hospedeiro. Além disso, o paciente apresentou repositivização da reação em cadeia da polimerase nasofaríngeo de SARS-CoV-2, com doença pregressa após iniciar tratamento com colírio de soro autólogo. As implicações a nível oftalmológico da infecção por SARS-CoV-2, podem ser esclarecidas à medida que a doença progride e aprendemos mais sobre sua forma de atuação. Neste caso, a disparidade de sinais e sintomas, o antecedente de cirurgia de córnea e a possibilidade de infecção herpética como causa do leucoma primário sugeriram ceratite neurotrófica. No entanto, deve-se levar em consideração o envolvimento da infecção sistêmica por SARS-CoV-2 no processo, desencadeando uma resposta imune excessiva do hospedeiro no nível da córnea, com aumento de citocinas inflamatórias. Não foi encontrada relação entre o tratamento com soro autólogo e a repositivização da reação em cadeia da polimerase nasofaríngea, apresentando ao paciente uma resposta favorável ao tratamento.

Avanços no entendimento da patogenia da Covid-19: uma revisão / Advances in understanding Covid-19 pathogenesis: a review / Avances en la comprensión de la patogenia de la Covid-19: una revisión

Introdução: O SARS-CoV-2, causador da pandemia por Doença por Coronavirus 2019 (COVID-19) gerou desafios à saúde pública, principalmente pelo conhecimento escasso de sua patogênese, e de estratégias terapêuticas e preventivas eficazes. Diversas lacunas de conhecimento sobre a doença envolvem a contribuição de fatores de risco, as doenças concomitantes, os fatores genéticos e imunogenéticos, no direcionamento da resposta imune, bem como a hiperinflamação, a imunidade antiviral e os alelos dos antígenos leucocitários humanos (HLAs) dos pacientes, que estão relacionados ao desfecho da doença. Objetivo: Esta revisão integrativa objetivou aprofundar os conhecimentos sobre os mecanismos de imunidade relacionada aos fatores de risco, da hiperinflamação e da tempestade de citocinas decorrente da infecção por SARS-CoV-2, bem como os avanços de associação dos HLAs nos agravos da doença. Metodologia: A revisão integrativa foi realizada utilizando os descritores nas bases de dados PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, Portal periódicos CAPES e Open Journal System, sem limites de janela cronológica. Resultados: Os efeitos da pandemia e os esforços na busca do conhecimento sobre a patogênese da COVID-19 resultaram em avanço no combate da doença. Conseguiu-se relacionar fatores de risco como obesidade, hipertensão, diabetes, doenças renais crônicas, idade, gênero, e outras condições predisponentes ao agravo da doença. Sob o aspecto da patogênese, também houveram progressos no entendimento dos mecanismos celulares e humorais em resposta à doença, bem como conseguiu vincular a resposta da hiperinflamação e o perfil dos HLAs dos pacientes à evolução da doença ao óbito ou à convalescência. Conclusão: Os esforços científicos conjuntos e os avanços na compreensão dos mecanismos da doença conseguiram estabelecer estratégias de combate a COVID-19, resultando no fim da pandemia, porém ainda há avanços que devem ser alcançados para o combate das sequelas dos pacientes convalescentes e para minimização da COVID longa e seus prejuízos.

Introduction: SARS-CoV-2, which causes the Coronavirus Disease 2019 (COVID-19) pandemic, has generated challenges to public health, mainly due to the limited knowledge of its pathogenesis and effective therapeutic and preventive strategies. Several gaps in knowledge about the disease involve the contribution of risk factors, concomitant diseases, genetic and immunogenetic factors, in directing the immune response, as well as hyperinflammation, antiviral immunity and human leukocyte antigen (HLAs) alleles of patients, which are related to the outcome of the disease. Aim: This integrative review aimed to deepen knowledge about the mechanisms of immunity related to risk factors, hyperinflammation and the cytokine storm resulting from SARS-CoV-2 infection, as well as advances in the association of HLAs in diseases. Methodology: The integrative review was carried out using the descriptors in the databases PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, CAPES periodical portal and Open Journal System, without chronological window limits. Results: The effects of the pandemic and efforts to seek knowledge about the pathogenesis of COVID-19 resulted in progress in combating the disease. It was possible to relate risk factors such as obesity, hypertension, diabetes, chronic kidney disease, age, gender, and other conditions predisposing to the worsening of the disease. From the aspect of pathogenesis, progress has also been made in understanding the cellular and humoral mechanisms in response to the disease, as well as linking the hyperinflammation response and the patients' HLA profile to the progression of the disease to death or convalescence. Conclusion: Joint scientific efforts and advances in understanding the mechanisms of the disease managed to establish strategies to combat COVID-19, resulting in the end of the pandemic, but there are still advances that must be achieved to combat the sequelae of convalescent patients and to minimize of long COVID and its losses.

Introducción: El SARS-CoV-2, causante de la pandemia de la Enfermedad del Coronavirus 2019 (COVID-19), ha generado desafíos a la salud pública, principalmente por el limitado conocimiento de su patogénesis y estrategias terapéuticas y preventivas efectivas. Varios vacíos en el conocimiento sobre la enfermedad involucran la contribución de factores de riesgo, enfermedades concomitantes, factores genéticos e inmunogenéticos, en la dirección de la respuesta inmune, así como la hiperinflamación, la inmunidad antiviral y los alelos del antígeno leucocitario humano (HLA) de los pacientes, que están relacionados con el resultado de la enfermedad. Objetivo: Esta revisión integradora tuvo como objetivo profundizar el conocimiento sobre los mecanismos de inmunidad relacionados con los factores de riesgo, la hiperinflamación y la tormenta de citocinas resultante de la infección por SARS-CoV-2, así como los avances en la asociación de los HLA en las complicaciones de la enfermedad. Metodología: La revisión integradora se realizó utilizando los descriptores de las bases de datos PubMed, SCIELO, CINAHL, SCOPUS, Web of Science, MedNar, portal periódico CAPES y Open Journal System, sin límites de ventana cronológica. Resultados: Los efectos de la pandemia y los esfuerzos por buscar conocimiento sobre la patogénesis de la COVID-19 resultaron en avances en el combate de la enfermedad. Se logró relacionar factores de riesgo como obesidad, hipertensión, diabetes, enfermedad renal crónica, edad, sexo y otras condiciones que predisponen al agravamiento de la enfermedad. Desde el punto de vista de la patogénesis, también se ha avanzado en la comprensión de los mecanismos celulares y humorales de respuesta a la enfermedad, así como en la vinculación de la respuesta de hiperinflamación y el perfil HLA de los pacientes con la progresión de la enfermedad hasta la muerte o la convalecencia. Conclusión: Los esfuerzos científicos conjuntos y los avances en la comprensión de los mecanismos de la enfermedad lograron establecer estrategias para combatir el COVID-19, teniendo como resultado el fin de la pandemia, pero aún quedan avances que se deben lograr para combatir las secuelas de los pacientes convalecientes y para Minimizar el COVID prolongado y sus pérdidas.

Inefficacious drugs against covid-19: analysis of sales, tweets, and search engines / Medicamentos ineficazes contra covid-19: análise de vendas, tweets e mecanismos de busca

ABSTRACT OBJECTIVE Assess the correlation between the sales of two drugs with no proven efficacy against covid-19, ivermectin and chloroquine, and other relevant variables, such as Google® searches, number of tweets related to these drugs, number of cases and deaths resulting from covid-19. METHODS The methodology adopted in this study has four stages: data collection, data processing, exploratory data analysis, and correlation analysis. Spearman's method was used to obtain cross-correlations between each pair of variables. RESULTS The results show similar behaviors between variables. Peaks occurred in the same or near periods. The exploratory data analysis showed shortage of chloroquine in the period corresponding to the beginning of advertising for the application of these drugs against covid-19. Both drugs showed a high and statistically significant correlation with the other variables. Also, some of them showed a higher correlation with drug sales when we employed a one-month lag. In the case of chloroquine, this was observed for the number of deaths. In the case of ivermectin, this was observed for the number of tweets, cases, and deaths. CONCLUSIONS The results contribute to decision making in crisis management by governments, industries, and stores. In times of crisis, as observed during the covid-19 pandemic, some variables can help sales forecasting, especially Google® and tweets, which provide a real-time analysis of the situation. Monitoring social media platforms and search engines would allow the determination of drug use by the population and better prediction of potential peaks in the demand for these drugs.

RESUMO OBJETIVO Investigar a correlação entre as vendas de dois medicamentos sem eficácia comprovada no tratamento de covid-19, ivermectina e cloroquina, e outras variáveis relevantes: pesquisas no Google®, número de tweets relacionados aos medicamentos, casos e óbitos decorrentes da covid-19. MÉTODOS A metodologia adotada neste estudo se divide em quatro partes: coleta de dados; processamento dos dados; análise exploratória; e análise de correlação. Foi utilizado o método de Spearman para obter as correlações cruzadas entre cada par de variáveis. RESULTADOS Os resultados mostram similaridade entre os comportamentos das variáveis. Os picos ocorreram em períodos iguais ou próximos. A análise exploratória dos dados apontou que houve falta de cloroquina no período correspondente ao início das divulgações sobre a aplicação desses medicamentos para o tratamento da covid-19. Ambos os medicamentos apresentaram correlação alta e estatisticamente significativa com as demais variáveis analisadas. Também foi observado que algumas delas apresentaram maior correlação com as vendas de medicamentos quando assumiram defasagem temporal de um mês. No caso da cloroquina, isso ocorreu com a variável óbitos. No caso da ivermectina, ocorreu com as variáveis número de tweets, casos e óbitos. CONCLUSÕES Os resultados observados contribuem para a tomada de decisão durante a gestão de crises por parte de governo, indústrias e comércios. Em momentos de crises, como observado durante a pandemia, as variáveis mostraram que são capazes de auxiliar na previsão de vendas, em especial o Google® e os tweets, que proporcionam uma análise em tempo real da situação. Acompanhar as redes sociais e mecanismos de busca permitiria detecção de uso pela população e melhor previsão de potenciais picos de demanda desses medicamentos.

Capacidad de procesamiento de los nanofiltros empleados en la purificación de la proteína recombinante del dominio de unión al receptor del coronavirus tipo 2 del síndrome respiratorio agudo severo / Processability of nanofilters used in the purification of the recombinant receptor-binding domain protein of severe acute respiratory syndrome type 2 coronavirus

En el Centro de Inmunología Molecular se producen el ingrediente farmacéutico activo y la materia prima biológica empleados para la formulación de las vacunas SOBERANAS®. El antígeno de estas vacunas es la proteína del dominio de unión al receptor del coronavirus tipo 2 del síndrome respiratorio agudo severo. La producción de esta proteína recombinante se basa en el cultivo de células de ovario de hámster chino en biorreactores tipo tanque agitado. El proceso tecnológico a escala industrial consta de varias etapas: preparación de medios de cultivo y soluciones, fermentación, clarificación de sobrenadante y purificación. En los procesos biotecnológicos derivados de líneas celulares de origen animal, la contaminación viral endógena o adventicia constituye un riesgo potencial. Por tal motivo, en el proceso de purificación se emplea un paso específico para la remoción viral mediante la nanofiltración. Los nanofiltros empleados son materiales desechables que influyen significativamente en el costo del proceso. Actualmente se desconoce la capacidad de procesamiento de los nanofiltros en el proceso de purificación en cuestión, siendo el objetivo de la presente investigación con vistas a reducir los costos de producción. Se determinó la capacidad de procesamiento de los filtros Virosart CPV, siendo de 239,74 g/m2 (71,67 por ciento de saturación) y 1.259 g/m2 (67,82 por ciento de saturación) para la especie dímero y la mezcla, respectivamente. Se determinó la disminución del costo de producción de la etapa de nanofiltración, que representa una disminución del 54,85 por ciento del costo de filtración de la especie dímero y un 25 por ciento de la mezcla(AU)

The active pharmaceutical ingredient and the biological raw material, used for the formulation of the SOBERANA® vaccines, are produced at the Molecular Immunology Center. The antigen of these vaccines is the receptor-binding domain protein of the severe acute respiratory syndrome type 2 coronavirus. The production of this recombinant protein is based on the culture of Chinese hamster ovary cells in stirred tank bioreactors. The technological process on an industrial scale consists of several stages: preparation of culture media and solutions, fermentation, clarification of supernatant and purification. In biotechnological processes derived from cell lines of animal origin, endogenous or adventitious viral contamination is a potential risk. For this reason, a specific step for viral removal by nanofiltration is used in the purification process. The nanofilters used are disposable materials that significantly influence the cost of the process. The processing capacity of the nanofilters in the purification process in question is currently unknown, being the objective of the present investigation with a view to reducing production costs. The processing capacity of the Virosart CPV filters was determined to be 239.74 g/m2 (71.67percent saturation) and 1,259 g/m2 (67.82percent saturation) for the dimer species and the mixture, respectively. The decrease in the production cost of the nanofiltration stage was determined, representing a 54.85percent decrease in the filtration cost for the dimer species and a 25percent decrease for the mixture(AU)

Boletim epidemiológico / Epidemiological bulletin

Abrange diversos tópicos relacionados à vigilância genômica do SARS-CoV-2, destacando a estratégia liderada pela Organização Mundial de Saúde e sua implementação descentralizada no Brasil, bem como o impacto epidemiológico das variantes identificadas. Além disso, comemora-se os 50 anos do Programa Nacional de Imunizações do Brasil, ressaltando sua importância na proteção da saúde da população através da vacinação. O texto também discute perspectivas futuras, incluindo o fortalecimento e expansão da vigilância genômica para outras doenças de interesse epidemiológico local. Na segunda parte, são mencionadas referências científicas relevantes sobre a COVID-19, incluindo artigos de periódicos renomados e estudos sobre a classificação da variante Omicron e suas subvariantes.

Covers various topics related to genomic surveillance of SARS-CoV-2, highlighting the strategy led by the World Health Organization and its decentralized implementation in Brazil, as well as the epidemiological impact of the identified variants. Additionally, the 50th anniversary of Brazil's National Immunization Program is celebrated, emphasizing its importance in protecting the population's health through vaccination. The text also discusses future perspectives, including strengthening and expanding genomic surveillance for other locally epidemiologically significant diseases. The second part mentions relevant scientific references on COVID-19, including articles from renowned journals and studies on the classification of the Omicron variant and its subvariants.

Aborda varios temas relacionados con la vigilancia genómica del SARS-CoV-2, destacando la estrategia liderada por la Organización Mundial de la Salud y su implementación descentralizada en Brasil, así como el impacto epidemiológico de las variantes identificadas. Además, se celebra el 50 aniversario del Programa Nacional de Inmunizaciones de Brasil, enfatizando su importancia en la protección de la salud de la población a través de la vacunación. El texto también discute perspectivas futuras, incluyendo el fortalecimiento y la expansión de la vigilancia genómica para otras enfermedades de interés epidemiológico local. En la segunda parte, se mencionan referencias científicas relevantes sobre COVID-19, incluyendo artículos de revistas de renombre y estudios sobre la clasificación de la variante Omicron y sus subvariantes.

The impact of the SARS-CoV-2 pandemic on tuberculosis notifications and deaths in the state of São Paulo, Brazil: a cross-sectional study

Background The state of São Paulo reports the highest number of tuberculosis cases in Brazil. We aimed to analyze the SARS-CoV-2 pandemic's impact on tuberculosis notifications and identify factors associated with reduced notifications and tuberculosis deaths in 2020­2021. Methods This retrospective cross-sectional study analyzed data from 126,649 patients with tuberculosis notified in São Paulo from 2016 to 2021. Interrupted time series analysis assessed the pandemic's impact on notifications. Descriptive statistics and logistic regressions identified factors associated with decreased tuberculosis notifications and deaths during the pandemic (2020­2021) compared to the pre-pandemic period (2019). Findings Tuberculosis notifications decreased by 10% and 8% in 2020 and 2021, espectively, with declines 2­3 times higher among individuals with no education or deprived of liberty. Contrastingly, tuberculosis notifications increased 68% among corrections workers in 2021. Diagnostics and contact tracing were compromised. Individuals with HIV, drug addiction, or deprived of liberty had lower odds of notification during the pandemic. Black and Pardo individuals or those with diabetes, treatment interruption history, or treatment changes post-adverse events had higher odds of notification. However, adverse events and tuberculosis-diabetes cases have been increasing since 2016. During the pandemic, tuberculosis-related deaths rose 5.0%­12.7%. Risk factors for mortality remained similar to 2019, with Pardo ethnicity, drug addiction and re-treatment post-adverse events emerging as risk factors in 2020/2021. Interpretation The pandemic affected tuberculosis notifications and deaths differently among populations, exacerbating inequalities. Treatment interruption, loss of follow-up, and challenges in accessing healthcare led to increased mortality. (AU)

Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells

BACKGROUND: Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. RESULTS: Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-ß, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. CONCLUSIONS: Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.

Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos / Seroprevalence of SARS-CoV-2 antibodies in patients with immune-mediated inflammatory diseases treated with biological and synthetic targeted therapies

INTRODUCCIÓN: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. OBJETIVO: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. MÉTODOS: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. RESULTADOS: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). CONCLUSIONES: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

BACKGROUND: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. AIM: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. METHODS: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. RESULTS: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). CONCLUSIONS: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.