Multicenter study of the natural history and therapeutic responses of patients with chikungunya, focusing on acute and chronic musculoskeletal manifestations - a study protocol from the clinical and applied research in Chikungunya (REPLICK network).

BACKGROUND: Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. METHODS: The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science - comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. DISCUSSION: Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines.

Uma análise dos principais diagnósticos de Sars-cov-2 disponíveis no Brasil: uma revisão de literatura / Diagnosis and main types of coronavirus in humans: a narrative review / Diagnóstico y principales tipos de coronavirus en humanos: una revisión narrativa

Introdução: Com a emergência do SARS-CoV-2 foi disponibilizado uma grande quantidade de ferramentas de diagnóstico. Neste contexto, a falta de vacina, de tratamento e o grande número de casos graves e morte, possibilitou a aprovação emergencial de diversos testes, que ainda necessitam de estudos populacionais para seu registro definitivo. Objetivo: Realizar uma revisão de literatura para avaliar as metodologias de diagnóstico disponíveis no Brasil, de acordo com a realidade local de saúde, explorando o momento epidemiológico a complexidade do teste e a finalidade da sua aplicação. Metodologia: Trata-se de um estudo bibliográfico, descritivo do tipo revisão de literatura. Foram utilizadas as seguintes bases de dados científicos para buscas: PUBMED, MEDLINE, LILACS E COCHRANE LIBRARY, através de descritores selecionados na plataforma DECS. Resultados: O cenário de diversos ensaios, baseados em diferentes metodologias, como os testes baseados em RNA viral, em detecção de antígenos virais ou de anticorpos, associados ao conhecimento da história natural do vírus, possibilita uma análise crítica do melhor diagnóstico de acordo com a clínica do paciente, os epidemiológicos, o objetivo do diagnóstico e a acurácia do ensaio. Atualmente, há mudança no padrão imunológico da população e a descrição de tipos e subtipos de SARS-CoV-2 com mudanças gênicas, que podem levar a mudanças na acurácia diagnóstica ou a re-emergência em surtos de doença grave. Conclusão: Ainda é incerto o caminho evolutivo da história natural da Covid-19 e os ensaios diagnósticos estão em diferentes estágios de desenvolvimento, validação e produção e cada tipo de teste tem suas próprias vantagens e desvantagens distintas inerentes a plataforma tecnológica de origem e uma combinação de tipos de testes usados em momentos diferentes pode ser útil para a condução clínica dos pacientes e no controle da pandemia por SARS-CoV-2.

Introduction: With the emergence of SARS-CoV-2, a large number of diagnostic tools were made available. In this context, the lack of vaccine, treatment and the large number of severe cases and death, allowed the emergency approval of several tests, which still require population studies for their definitive registration. Objective: To carry out a literature review to evaluate the diagnostic methodologies available in Brazil, according to the local health reality, exploring the epidemiological moment, the complexity of the test and the purpose of its application. Methodology: This is a bibliographic, descriptive study of the literature review type. The following scientific databases were used for searches: PUBMED, MEDLINE, LILACS AND COCHRANE LIBRARY, through selected descriptors on the DECS platform. Results: The scenario of several tests, based on different methodologies, such as tests based on viral RNA, on detection of viral antigens or antibodies, associated with knowledge of the natural history of the virus, allows a critical analysis of the best diagnosis according to the patient's clinical, epidemiological, diagnostic objective and assay accuracy. Currently, there is a change in the immune pattern of the population and the description of types and subtypes of SARS-CoV-2 with genetic changes, which can lead to changes in diagnostic accuracy or the re-emergence in outbreaks of severe disease. Conclusion: The evolutionary path of the natural history of Covid-19 is still uncertain and diagnostic assays are at different stages of development, validation and production and each type of test has its own distinct advantages and disadvantages inherent in the technology platform of origin and a combination of types of tests used at different times can be useful for the clinical management of patients and in the control of the SARS-CoV-2 pandemic.

Introducción: Con la aparición del SARS-CoV-2, se dispuso de un gran número de herramientas diagnósticas. En este contexto, la falta de vacuna, tratamiento y el gran número de casos graves y muerte, permitieron la aprobación de urgencia de varias pruebas, que aún requieren estudios poblacionales para su registro definitivo. Objetivo: Realizar una revisión bibliográfica para evaluar las metodologías diagnósticas disponibles en Brasil, de acuerdo con la realidad sanitaria local, explorando el momento epidemiológico, la complejidad de la prueba y la finalidad de su aplicación. Metodología: Se trata de un estudio bibliográfico, descriptivo, del tipo revisión de literatura. Para las búsquedas se utilizaron las siguientes bases de datos científicas PUBMED, MEDLINE, LILACS Y COCHRANE LIBRARY, a través de descriptores seleccionados en la plataforma DECS. Resultados: El escenario de varias pruebas, basadas en diferentes metodologías, como pruebas basadas en el ARN viral, en la detección de antígenos virales o anticuerpos, asociado al conocimiento de la historia natural del virus, permite un análisis crítico del mejor diagnóstico de acuerdo con la clínica del paciente, epidemiológica, objetivo diagnóstico y precisión de la prueba. Actualmente, hay un cambio en el patrón inmunológico de la población y la descripción de tipos y subtipos de SARS-CoV-2 con cambios genéticos, que pueden conducir a cambios en la precisión diagnóstica o la reaparición en brotes de enfermedad grave. Conclusiones: El camino evolutivo de la historia natural del Covid-19 es aún incierto y los ensayos de diagnóstico se encuentran en diferentes etapas de desarrollo, validación y producción y cada tipo de prueba tiene sus propias ventajas y desventajas distintas inherentes a la plataforma tecnológica de origen y una combinación de tipos de pruebas utilizadas en diferentes momentos puede ser útil para el manejo clínico de los pacientes y en el control de la pandemia de SARS- CoV-2.

Avaliação da gravidade (pim ii), funcionalidade (fss) e de desconforto respiratório (bsa) nos impactos e desfechos da internação hospitalar em utip / Assessment of severity (pim ii), functionality (fss) and of respiratory distress (bsa) in the impacts and outcomes of hospital admission in utip / Valoración de la gravedad (pim ii), funcionalidad (fss) y de la dificultad respiratoria (bsa) en los impactos y resultados del ingreso hospitalario en utip

Objetivo: identificar o perfil de admissões e o impacto nos desfechos de crianças internadas em uma terapia intensiva pediátrica e comparar os escores de gravidade, funcionalidade e de desconforto respiratório avaliados respectivamente pelas escalas (PIM II, FSS e BSA). Métodos: Estudo de caráter descritivo, retrospectivo, quantitativo de amostragem censitária. Ferramentas de avaliação: Pediatric Index of Mortality - PIM II, Functional Status Scoret -FSS, Boletim de Silverman-Andersen -BSA e avaliação de prontuários médicos e assistenciais. Resultados: 257 crianças menores de 12 anos foram incluídas no estudo durante todo o ano de 2019. A maioria 56% (n 143) eram menores de um ano e masculino 64 % (n 164) por causas respiratórias 60,05 % (n 155). A mortalidade foi de 9,8% (n 25), e a quantidade média de dias de ventilação mecânica foi de 4,57 dias ± 1,31. A idade não influenciou na quantidade de dias de ventilação mecânica (p<0.05), e o BSA avaliado isoladamente, não se associou a necessidade imediata de intubação (p<0.05), os pacientes do desfecho óbito ficaram em média 8,88 e ±13,04 dias internados, e no desfecho alta 4,73 ±6,63 dias. O PIM II pode ser utilizado para o risco de óbito (p <0,05) e valores maiores ou iguais a 21,58 % foram associados a óbitos e menores ou iguais a 6,65 % foram associados à alta. A FSS dos 257 pacientes na admissão foram: normal (147), disfunção leve (37), moderada (47) e grave (26); na alta hospitalar a FSS foi: normal (178), leve (21), moderada (25) e grave (8) mostrando que grau de funcionalidade normal e leve na admissão esta significativamente associado com a alta hospitalar (p< 0,001). Conclusão: O escore de gravidade PIM II foram compatíveis com os desfechos óbito ou alta, as variações no escore BSA para necessidade de ventilação mecânica não estão associados com a idade e com grau do escore. A funcionalidade mais adequada na admissão está associada ao desfecho alta, e os pacientes em sua maioria saem funcionais.

Objective: To identify the profile of admissions and the impact on outcomes of children admitted to a pediatric intensive care unit and to compare severity, functionality and respiratory distress scores assessed respectively by the scales (PIM II, FSS and BSA). Methods: This was a descriptive, retrospective, quantitative study with census sampling. Assessment tools: Pediatric Index of Mortality - PIM II, Functional Status Scoret -FSS, Silverman-Andersen Bulletin -BSA and assessment of medical and health care records. Results: 257 children under the age of 12 years were included in the study throughout 2019. The majority 56% (n 143) were under one year and male 64 % (n 164) from respiratory causes 60.05 % (n 155). Mortality was 9.8% (n 25), and the average amount of days on mechanical ventilation was 4.57 days ± 1.31. Age had no influence on the number of days of mechanical ventilation (p<0.05), and the BSA assessed alone was not associated with the immediate need for intubation (p<0.05), the patients in the outcome death were hospitalized for an average of 8.88 ±13.04 days, and in the discharge outcome 4.73 ±6.63 days. The PIM II can be used for the risk of death (p <0.05) and values greater than or equal to 21.58 % were associated with death and less than or equal to 6.65 % were associated with discharge. The FSS of the 257 patients at admission were: normal (147), mild (37), moderate (47) and severe (26) dysfunction; at hospital discharge the FSS was: normal (178), mild (21), moderate (25) and severe (8) showing that the degree of normal and mild functionality at admission was significantly associated with hospital discharge (p < 0.001). Conclusion: The PIM II severity scores were compatible with the outcomes death or discharge, the variations in BSA score for mechanical ventilation need were not associated with age and score level. The most adequate functionality at admission is associated with the outcome discharge, and most patients leave the hospital functional.

Objetivo: Identificar el perfil de ingreso y el impacto en los resultados de los niños ingresados en una unidad de cuidados intensivos pediátricos y comparar las puntuaciones de gravedad, funcionalidad y distrés respiratorio evaluadas respectivamente por las escalas (PIM II, FSS y BSA). Métodos: Se trató de un estudio descriptivo, retros- pectivo y cuantitativo con muestreo censal. Instrumentos de evaluación: Índice de Mor- talidad Pediátrica - PIM II, Functional Status Scoret -FSS, Boletín de Silverman-Ander- sen -BSA y evaluación de historias clínicas y asistenciales. Resultados: 257 niños meno- res de 12 años fueron incluidos en el estudio a lo largo de 2019. La mayoría 56% (n 143) eran menores de un año y varones 64% (n 164) de causas respiratorias 60,05% (n 155). La mortalidad fue del 9,8% (n 25) y la media de días con ventilación mecánica fue de 4,57 días ± 1,31. La edad no influyó en el número de días de ventilación mecánica (p<0,05), y el BSA evaluado por sí solo no se asoció con la necesidad inmediata de intu- bación (p<0,05), los pacientes en el resultado muerte estuvieron hospitalizados una media de 8,88 ±13,04 días, y en el resultado alta 4,73 ±6,63 días. El PIM II se puede utilizar para el riesgo de muerte (p <0,05) y los valores mayores o iguales a 21,58 % se asociaron con la muerte y menores o iguales a 6,65 % se asociaron con el alta. La SFS de los 257 pacientes al ingreso fue: normal (147), disfunción leve (37), moderada (47) y grave (26); al alta hospitalaria la SFS fue: normal (178), leve (21), moderada (25) y grave (8) mos- trando que el grado de funcionalidad normal y leve al ingreso se asoció significativamente con el alta hospitalaria (p < 0,001). Conclusiones: Las puntuaciones de gravedad del PIM II fueron compatibles con los resultados muerte o alta hospitalaria, las variaciones en la puntuación del BSA para la necesidad de ventilación mecánica no se asociaron con la edad y el nivel de puntuación. La funcionalidad más adecuada al ingreso se asocia con el resultado alta, y la mayoría de los pacientes salen del hospital funcionales.

Serum biomarkers associated with SARS-CoV-2 severity.

Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.