Pediatric patients with COVID-19 admitted to intensive care units in Brazil: a prospective multicenter study / Pacientes pediátricos com COVID-19 admitidos em Unidades de Terapia Intensiva no Brasil: um estudo prospectivo multicêntrico

Abstract Objective: To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID-19. Method: Prospective, multicenter, observational study, in 19 pediatric intensive care units. Patients aged 1 month to 19 years admitted consecutively (March-May 2020) were included. Demographic, clinical-epidemiological features, treatment, and outcomes were collected. Subgroups were compared according to comorbidities, age < 1 year, and need for invasive mechanical ventilation. A multivariable logistic regression model was used for predictors of severity. Results: Seventy-nine patients were included (ten with multisystemic inflammatory syndrome). Median age 4 years; 54% male (multisystemic inflammatory syndrome, 80%); 41% had comorbidities (multisystemic inflammatory syndrome, 20%). Fever (76%), cough (51%), and tachypnea (50%) were common in both groups. Severe symptoms, gastrointestinal symptoms, and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome. Interstitial lung infiltrates were common in both groups, but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group (43% vs. 14%). Invasive mechanical ventilation was used in 18% (median 7.5 days); antibiotics, oseltamivir, and corticosteroids were used in 76%, 43%, and 23%, respectively, but not hydroxychloroquine. The median pediatric intensive care unit length-of-stay was five days; there were two deaths (3%) in the non- multisystemic inflammatory syndrome group. Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation (OR 5.5; 95% CI, 1.43-21.12; p = 0.01). Conclusions: In Brazilian pediatric intensive care units, COVID-19 had low mortality, age less than 1 year was not associated with a worse prognosis, and patients with multisystemic inflammatory syndrome had more severe symptoms, higher inflammatory biomarkers, and a greater predominance of males, but only comorbidities and chronic diseases were independent predictors of severity.

Resumo Objetivo: Descrever as características clínicas de crianças e adolescentes internados em unidade de terapia intensiva com COVID-19 confirmada. Método: Estudo prospectivo, multicêntrico, observacional, em 19 unidades de terapia intensiva pediátrica. Foram incluídos pacientes entre um mês e 19 anos, admitidos consecutivamente (março a maio de 2020). As características demográficas, clínico-epidemiológicas, o tratamento e os resultados foram coletados. Os subgrupos foram comparados de acordo com as comorbidades, idade < 1 ano e necessidade de ventilação mecânica invasiva. Um modelo de regressão logística multivariável foi utilizado para preditores de gravidade. Resultados: Setenta e nove pacientes foram incluídos (10 com síndrome inflamatória multi-ssistêmica). Mediana de idade, quatro anos; 54% eram do sexo masculino (síndrome inflamatória multissistêmica, 80%); 41% tinham comorbidades (síndrome inflamatória multissistêmica, 20%). Febre (76%), tosse (51%) e taquipneia (50%) foram comuns nos dois grupos. Sintomas graves egastrointestinais e marcadores inflamatórios mais elevados foram mais frequentes na presença de síndrome inflamatória multissistêmica. Infiltrados intersticiais pulmonares foram comuns em ambos os grupos, mas o derrame pleural foi mais prevalente no grupo com síndrome inflamatória multissistêmica (43% vs. 14%). A ventilação mecânica invasiva foi utilizada em 18% (mediana 7,5 dias); antibióticos, oseltamivir e corticosteroides foram utilizados em 76%, 43% e 23%, respectivamente, mas não a hidroxicloroquina. A mediana do tempo de permanência na unidade de terapia intensiva pediátrica foi de 5 dias; duas mortes ocorreram (3%) no grupo não- síndrome inflamatória multissistêmica. Os pacientes com comorbidades eram mais velhos, e as comorbidades foram independentemente associadas à necessidade de ventilação mecânica invasiva(OR 5,5; IC95%, 1,43-21,12; P 0,01). Conclusões: Nas unidades de terapia intensiva pediátrica brasileiras, a COVID-19 apresentou baixa mortalidade, a idade inferior a um ano não foi associada a um pior prognóstico, os pacientes com síndrome inflamatória multissistêmica apresentaram sintomas mais graves, biomarcadores inflamatórios mais elevados e uma grande predominância no sexo masculino, mas apenas a presença de comorbidades e doenças crônicas foi um preditor independente de gravidade.

Pediatric patients with COVID-19 admitted to intensive care units in Brazil: a prospective multicenter study.

OBJECTIVE: To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID-19. METHOD: Prospective, multicenter, observational study, in 19 pediatric intensive care units. Patients aged 1 month to 19 years admitted consecutively (March-May 2020) were included. Demographic, clinical-epidemiological features, treatment, and outcomes were collected. Subgroups were compared according to comorbidities, age < 1 year, and need for invasive mechanical ventilation. A multivariable logistic regression model was used for predictors of severity. RESULTS: Seventy-nine patients were included (ten with multisystemic inflammatory syndrome). Median age 4 years; 54% male (multisystemic inflammatory syndrome, 80%); 41% had comorbidities (multisystemic inflammatory syndrome, 20%). Fever (76%), cough (51%), and tachypnea (50%) were common in both groups. Severe symptoms, gastrointestinal symptoms, and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome. Interstitial lung infiltrates were common in both groups, but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group (43% vs. 14%). Invasive mechanical ventilation was used in 18% (median 7.5 days); antibiotics, oseltamivir, and corticosteroids were used in 76%, 43%, and 23%, respectively, but not hydroxychloroquine. The median pediatric intensive care unit length-of-stay was five days; there were two deaths (3%) in the non- multisystemic inflammatory syndrome group. Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation (OR 5.5; 95% CI, 1.43-21.12; p = 0.01). CONCLUSIONS: In Brazilian pediatric intensive care units, COVID-19 had low mortality, age less than 1 year was not associated with a worse prognosis, and patients with multisystemic inflammatory syndrome had more severe symptoms, higher inflammatory biomarkers, and a greater predominance of males, but only comorbidities and chronic diseases were independent predictors of severity.

Rio Birth Cohort Study on Environmental Exposure and Childhood Development - PIPA Project.

Background/Objective: As a developing country, Brazil presents a wide range of environmental risks that can constitute hazards to child health. The country also presents different socio-economic-cultural conditions that could be responsible for determining different vulnerability and susceptibility levels for the population, which can potentiate the effects of the environmental pollutants. The Rio Birth Cohort Study (PIPA project) is a prospective maternal-infant health study, hosted in the city of Rio de Janeiro (Southeastern Brazil), designed to investigate separate and combined effects of environmental chemical pollutants, as well as the interactions between these exposures and sociocultural environment and epigenetic patterns. This paper presents the learned lessons and strategies to address the shortcomings detected from this pilot study. Methods: The study population will be all children born at the Federal University of Rio de Janeiro Maternity Hospital from July 1st, 2020 to June 30th, 2021. The estimated population is of 2,500 children. The study will collect social, demographic, and health information from pregnant women and their children up to four years of age. Biological samples from both mothers and newborns will be collected to assess metal, pesticide and plasticizer exposure. All newborns will have their landmarks of physical, neurological, psychological, and cognitive development recorded at specific ages. Findings: A pilot study was carried out between September 2017 and August 2018, totaling 142 enrolled pregnant women, leading to 135 (95%) births and the collection of umbilical cord (126-93%,) and mother (139-98%) blood samples, as well as both mother (142-100%) and newborn (54-40%) urine samples and newborn meconium samples (117-86.7%). Conclusions: The study proposes a comprehensive assessment of pre- and postnatal exposure to environmental chemicals at multiple time points in a population living in a highly urbanized developing country. As far as we know, this is the only birth cohort in Brazil specifically designed for this purpose.

Lethality by pneumonia and factors associated to death / Letalidade por pneumonia e fatores associados ao óbito

OBJECTIVE: To describe the case-fatality rate (CFR) and risk factors of death in children with community-acquired acute pneumonia (CAP) in a pediatric university hospital. METHOD: A longitudinal study was developed with prospective data collected from 1996 to 2011. Patients aged 1 month to 12 years were included in the study. Those who left the hospital against medical orders and those transferred to ICU or other units were excluded. Demographic andclinical-etiological characteristics and the initial treatment were studied. Variables associated to death were determined by bivariate and multivariate analysis using logistic regression. RESULTS: A total of 871 patients were selected, of whom 11 were excluded; thus 860 children were included in the study. There were 26 deaths, with a CFR of 3%; in 58.7% of these, penicillin G was the initial treatment. Pneumococcus was the most common pathogen (50.4%). From 1996 to 2000, there were 24 deaths (93%), with a CFR of 5.8% (24/413). From 2001 to 2011, the age group of hospitalized patients was older (p = 0.03), and the number of deaths (p = 0.02) and the percentage of disease severity were lower (p = 0.06). Only disease severity remained associated to death in the multivariate analysis (OR = 3.2; 95%CI: 1.2-8.9; p = 0.02). CONCLUSION: When the 1996-2000 and 2001-2011 periods were compared, a significant reduction in CFR was observed in the latter, as well as a change in the clinical profile of the pediatric in patients at the institute. These findings may be related to the improvement in the socio-economical status of the population. Penicillin use did not influence CFR. .

OBJETIVO: Descrever a taxa de letalidade (TL) e os fatores de risco de óbito em crianças com pneumonia grave adquirida na comunidade (CAP) em um hospital universitário pediátrico. MÉTODO: Foi desenvolvido um estudo longitudinal com dados prospectivos coletados de 1996 a2011. Foram incluídos no estudo pacientes com idade entre 1 mês e 12 anos de idade. Foram excluídos aqueles que deixaram o hospital desconsiderando as recomendações médicas e aqueles transferidos para UTI ou outras unidades. Foram estudadas as características demográficas, clínicas e etiológicas e o tratamento inicial. As variáveis associadas a óbito foram determinadas por análise bivariada e multivariada utilizando regressão logística. RESULTADOS: Foi selecionado um total de 871 pacientes, dos quais 11 foram excluídos; assim, foram incluídas no estudo 860 crianças. Houve 26 óbitos, com uma TL de 3%; em 58,7% desses, penicilina G foi o tratamento inicial. Pneumococo foi o patógeno mais comum (50,4%). De 1996 a 2000, houve 24 óbitos (93%), com uma TL de 5,8% (24/413). De 2001 a 2011, a faixa etária de pacientes internados foi mais velha (p = 0,03) e o número de óbitos (p = 0,02) e o percentual de gravidade das doenças foram menores (p = 0,06). Apenas a gravidade das doenças continuou associada a óbito na análise multivariada (RC = 3,2; IC de 95%: 1,2-8,9; p = 0,02). CONCLUSÃO: Quando os períodos de 1996-2000 e 2001-2011 foram comparados, foi observada uma redução significativa na TL no último período, bem como uma alteração no perfil clínico dos pacientes hospitalizados no instituto. Esses achados podem estar relacionados à melhora na situação socioeconômica da população. O uso de penicilina não influenciou a TL. .

Lethality by pneumonia and factors associated to death.

OBJECTIVE: To describe the case-fatality rate (CFR) and risk factors of death in children with community-acquired acute pneumonia (CAP) in a pediatric university hospital. METHOD: A longitudinal study was developed with prospective data collected from 1996 to 2011. Patients aged 1 month to 12 years were included in the study. Those who left the hospital against medical orders and those transferred to ICU or other units were excluded. Demographic and clinical-etiological characteristics and the initial treatment were studied. Variables associated to death were determined by bivariate and multivariate analysis using logistic regression. RESULTS: A total of 871 patients were selected, of whom 11 were excluded; thus 860 children were included in the study. There were 26 deaths, with a CFR of 3%; in 58.7% of these, penicillin G was the initial treatment. Pneumococcus was the most common pathogen (50.4%). From 1996 to 2000, there were 24 deaths (93%), with a CFR of 5.8% (24/413). From 2001 to 2011, the age group of hospitalized patients was older (p = 0.03), and the number of deaths (p = 0.02) and the percentage of disease severity were lower (p = 0.06). Only disease severity remained associated to death in the multivariate analysis (OR = 3.2; 95%CI: 1.2-8.9; p = 0.02). CONCLUSION: When the 1996-2000 and 2001-2011 periods were compared, a significant reduction in CFR was observed in the latter, as well as a change in the clinical profile of the pediatric inpatients at the institute. These findings may be related to the improvement in the socio-economical status of the population. Penicillin use did not influence CFR.

Quality of life and its domains in leprosy patients after neurolysis: a study using WHOQOL-BREF.

Surgical nerve decompression in leprosy is indicated to prevent or treat nerve damage, and to improve sensory motor function and quality of life (QoL). The purpose of this study was to describe QoL of leprosy patients after surgical nerve decompression. Participants who underwent neurolysis in the last 5 years were recruited. The assessment consisted of collecting demographic and clinical information, QoL and its domain scores. Descriptive statistical analysis of demographic and clinical data was presented. Included 33 patients (43 +/- 11.0 years) who had neurolysis with a total of 61 nerves operated. The results of WHOQOL-bref showed that overall QoL mean was 11.2 (+/- 3.63) and domains scored as follow: physical (11.0 +/- 3.56), environment (11.47 +/- 2.11), psychological (13.29 +/- 2.79) and social relations (15.03 +/- 3.66). Measures of QoL should become part of the standard battery of tools used to assess health and well-being and it may contribute to identifying patients' needs in rehabilitation.

Chronic pain in leprosy: new aspects to be considered.

Leprosy is still considered to be endemic in several developing countries, such as India and Brazil. Infection with Mycobacterium leprae leads to chronic granulomatous inflammation in skin and peripheral nerves that can lead to sensory, motor and autonomic impairments. Since the disease causes severe sensory loss, little attention has been given to pain in leprosy. However, chronic pain in leprosy is being increasingly recognized as an important late complication of leprosy. This article discusses the assessment of pain in leprosy and suggests factors that can contribute to the chronicity. We also consider pain as a multiple system output, bringing the possibility of new treatment options for chronic pain in leprosy.

Immunoreactivity of five antigens of Mycobacterium tuberculosis in patients attending a public health care facility in an area with high endemicity for TB.

The objective of this study was to evaluate people attending a primary health clinic in Rio de Janeiro, Brazil for immunoreactivity to five Mycobacterium tuberculosis antigens, as these antigens are markers of immune response and factors associated with active TB. The serum antibody titers of different categories of patients (defined by microbiological and radiological characteristics and by response to therapy on follow-up) to 38 kDa, 16 kDa, MPT64, ESAT-6 and MT10.3 antigens were determined blind with ELISA. Positive tests to each antigen were defined with ROC analysis. OR were calculated for factors associated with humoral response in patients with active TB. A total of 201 patients underwent serological testing. Patients with confirmed active TB responded more frequently to MPT64 (44%), 16 kDa (37.7%) and 38 kDa (36.1%). ESAT-6 and MT10.3 were also able to distinguish people in TB groups from controls. TB infected subjects responded less frequently to ESAT-6 and MT10.3 (3.7% and 11%, respectively). Sensitivity and specificity to all antigens combined were 58.4% and 60.7%, respectively. Reactivity to 38 kDa and to MPT64 was more likely among alcohol users OR 2.61 (95%CI;1.05-6.94) and OR 3.27 (95%CI;1.33-8.15), respectively. 16 kDa antigen elicited a more protective response among smokers, OR 0.29 (95%CI; 0.10-0.83). It was concluded that reactivity to all antigens tested represented markers of active disease. ESAT-6 and MT10.3 could not be identified as markers of TB infection in this community. Sensitivity was higher to all antigens combined, but at a cost of lower specificity. Interestingly, among factors associated with positive immunoreactivity, alcohol use and smoking seem to polarize the humoral response in different directions. This finding deserves further investigation.

Predictive model for the diagnosis of tuberculous pleural effusion.

This study developed a predictive model to identify pleural tuberculosis. A consecutive cases study of patients investigating the cause of pleural effusion, in an area of high prevalence of tuberculosis (Rio de Janeiro, Brazil). Clinical and laboratory variables were compared among patients with tuberculosis (TB) and without tuberculosis (NTB), individually and using logistic regression. The performance was described as diagnostic accuracy, compared to a gold standard in a masked way. We have studied 104 TB patients, 41 with malignant, 29 transudates, 28 parapneumonic, 13 with miscellaneous diseases. After identification of individual discrimination power aided by clinical, radiological and laboratory variables, the following ones were included in a multivariate analysis: ADA, total leukocytes, percentile of lymphocytes, protein, lactate dehydrogenase, duration of disease, age and gender. A logistic regression model to predict pleural tuberculosis including the five first variables showed the best performance. A receiver operating characteristic curve identified the best cutoff at 0.7, resulting in a sensitivity and specificity of more then 95%. The predictive model improved the specificity of ADA alone, keeping its sensitivity. This model seems helpful when a microbiological or histological diagnosis of pleural tuberculosis could not be established. External validation of these results is necessary before recommendation for routine application.

Predictive model for the diagnosis of tuberculous pleural effusion

This study developed a predictive model to identify pleural tuberculosis. A consecutive cases study of patients investigating the cause of pleural effusion, in an area of high prevalence of tuberculosis (Rio de Janeiro, Brazil). Clinical and laboratory variables were compared among patients with tuberculosis (TB) and without tuberculosis (NTB), individually and using logistic regression. The performance was described as diagnostic accuracy, compared to a gold standard in a masked way. We have studied 104 TB patients, 41 with malignant, 29 transudates, 28 parapneumonic, 13 with miscellaneous diseases. After identification of individual discrimination power aided by clinical, radiological and laboratory variables, the following ones were included in a multivariate analysis: ADA, total leukocytes, percentile of lymphocytes, protein, lactate dehydrogenase, duration of disease, age and gender. A logistic regression model to predict pleural tuberculosis including the five first variables showed the best performance. A receiver operating characteristic curve identified the best cutoff at 0.7, resulting in a sensitivity and specificity of more then 95 percent. The predictive model improved the specificity of ADA alone, keeping its sensitivity. This model seems helpful when a microbiological or histological diagnosis of pleural tuberculosis could not be established. External validation of these results is necessary before recommendation for routine application.

Tuberculin skin test conversion among medical students at a teaching hospital in Rio de Janeiro, Brazil.

OBJECTIVE: To describe the cumulative incidence of and risk factors for tuberculosis (TB) infection among medical students. DESIGN: In 1999, a cohort study of medical students with negative results (induration < 10 mm) on tuberculin skin test (TST) was performed. Students who had undergone two-step testing in 1998 were retested. SETTINGS: University and teaching hospital and referral center for TB and acquired immunodeficiency syndrome, and the Health Sciences Building of the Medical School of the Federal University of Rio de Janeiro, Brazil. PARTICIPANTS: A sample of 618 consecutive medical students with negative TST results who had been tested 12 months before were approached. Information about sociodemographic characteristics, bacille Calmette-Guérin vaccination history, and potential exposures to TB was obtained using a standardized questionnaire. Four hundred fourteen (67%) students completed the study. Students were at two different levels of their training programs (juniors = no contact with patients; seniors = intensive contact with patients). RESULTS: Of 414 participants, 16 (3.9%; 95% confidence interval, 1.06% to 12.1%) had converted to a positive reaction after 1 year. In a multivariate logistic regression analysis, higher level of clinical training was confirmed to be an independent factor associated with TST conversion (odds ratio, 4.77; 95% confidence interval, 1.01 to 22.46; P= .048). CONCLUSION: Senior medical students are at increased risk of Mycobacterium tuberculosis infection in this setting. Therefore, a program of routine tuberculin skin testing and specific TB infection control guidelines are needed for this population.