Management of severe traumatic brain injury in pediatric patients: an evidence-based approach.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. The decision-making process in the management of severe TBI must be based on the best available evidence to minimize the occurrence of secondary brain injuries. However, healthcare approaches to managing TBI patients exhibit considerable variation. METHODS: Over an 18-month period, a multidisciplinary panel consisting of medical doctors, physiotherapists, nutritional therapists, and nurses performed a comprehensive review on various subtopics concerning TBI. The panel identified primary questions to be addressed using the Population, Intervention, Control, and Outcome (PICO) format and applied the Evidence to Decision (EtD) framework criteria for evaluating interventions. Subsequently, the panel formulated recommendations for the management of severe TBI in children. RESULTS: Fourteen evidence-based recommendations have been devised for the management of severe TBI in children, covering nine topics, including imaging studies, neuromonitoring, prophylactic anticonvulsant use, hyperosmolar therapy, sedation and analgesia, mechanical ventilation strategies, nutritional therapy, blood transfusion, and decompressive craniectomy. For each topic, the panel provided clinical recommendations and identified research priorities. CONCLUSIONS: This review offers evidence-based strategies aimed to guide practitioners in the care of children who suffer from severe TBI.

Colloids for the Initial Management of Severe Sepsis and Septic Shock in Pediatric Patients: A Systematic Review.

AIM: The goal of this study was to perform a systematic review of the literature assessing the use of colloids for the initial treatment of severe sepsis and septic shock in pediatric patients. DESIGN: The PICO [Patient, Intervention, Comparison, Outcome] method was used for the selection of studies, and the Cochrane Bias Tool was used to analyze the quality of the selected studies. DATA SEARCH: Relevant studies were sought using the following databases: EMBASE (1980 to March 2014), PubMed (1970 to March 2014), Cochrane (1980 to March 2014), Web of Science, and Scopus. Searches used the following key words: isotonic solution, crystalloid, saline solution, colloid, resuscitation, fluid therapy, sepsis and septic shock, starch, and gelatin. The filters children and clinical trial were used when possible. REVIEW METHOD: Study selection was performed by 1 examiner. The selected articles were analyzed by 2 examiners who validated the articles according to the Cochrane Bias Tool. Discrepancies were resolved by consensus or by a third examiner. RESULT: A total of 110 articles were selected based on the key words. Of these, 99 were excluded because they assessed postoperative follow-up, burn cases, cardiac surgery, or nutritional therapy or were review articles, guidelines, or editorials. One study was included after an analysis of previous reviews. A total of 12 articles were selected for analysis because they were reports of clinical trials conducted with prospective cohorts and they analyzed the use of crystalloids and colloids or colloids only in the initial treatment of severe sepsis or septic shock in children and adolescents. The total number of patients was 4375, and they ranged in age from 2 months to 15 years, with most patients between 5 and 15 years. Five studies assessed patients diagnosed with malaria, 5 assessed patients with dengue shock syndrome, 1 studied febrile diseases, and 1 examined the progression of patients with septic shock caused by various causes. CONCLUSIONS: The studies analyzed did not find evidence to suggest that the use of colloids is superior to crystalloids. In some studies, the fluid volume needed to achieve initial stabilization was smaller in the group given colloids. Crystalloids are the preferred therapeutic option because of their effectiveness, low cost, and wide availability. Colloids may be the first choice in cases of malaria when the central nervous system is affected.

Technical performance of a lateral flow immunoassay for detection of anti-SARS-CoV-2 IgG in the outpatient follow-up of non-severe cases and at different times after vaccination: comparison with enzyme and chemiluminescent immunoassays.

This study assessed the technical performance of a rapid lateral flow immunochromatographic assay (LFIA) for the detection of anti-SARS-CoV-2 IgG and compared LFIA results with chemiluminescent immunoassay (CLIA) results and an in-house enzyme immunoassay (EIA). To this end, a total of 216 whole blood or serum samples from three groups were analyzed: the first group was composed of 68 true negative cases corresponding to blood bank donors, healthy young volunteers, and eight pediatric patients diagnosed with other coronavirus infections. The serum samples from these participants were obtained and stored in a pre-COVID-19 period, thus they were not expected to have COVID-19. In the second group of true positive cases, we chose to replace natural cases of COVID-19 by 96 participants who were expected to have produced anti-SARS-CoV-2 IgG antibodies 30-60 days after the vaccine booster dose. The serum samples were collected on the same day that LFIA were tested either by EIA or CLIA. The third study group was composed of 52 participants (12 adults and 40 children) who did or did not have anti-SARS-CoV-2 IgG antibodies due to specific clinical scenarios. The 12 adults had been vaccinated more than seven months before LFIA testing, and the 40 children had non-severe COVID-19 diagnosed using RT-PCR during the acute phase of infection. They were referred for outpatient follow-up and during this period the serum samples were collected and tested by CLIA and LFIA. All tests were performed by the same healthcare operator and there was no variation of LFIA results when tests were performed on finger prick whole blood or serum samples, so that results were grouped for analysis. LFIA's sensitivity in detecting anti-SARS-CoV-2 IgG antibodies was 90%, specificity 97.6%, efficiency 93%, PPV 98.3%, NPV 86.6%, and likelihood ratio for a positive or a negative result were 37.5 and 0.01 respectively. There was a good agreement (Kappa index of 0.677) between LFIA results and serological (EIA or CLIA) results. In conclusion, LFIA analyzed in this study showed a good technical performance and agreement with reference serological assays (EIA or CLIA), therefore it can be recommended for use in the outpatient follow-up of non-severe cases of COVID-19 and to assess anti-SARS-CoV-2 IgG antibody production induced by vaccination and the antibodies decrease over time. However, LFIAs should be confirmed by using reference serological assays whenever possible.

Influenza B infection and Kawasaki disease in an adolescent during the COVID-19 pandemic: a case report. / Infecção por Influenza B e doença de Kawasaki em adolescente durante a pandemia da COVID-19: relato de caso.

We report a case of Influenza B infection and Kawasaki disease in an adolescent, diagnosed during the COVID-19 pandemic. An asthmatic female adolescent presented with fever and flu-like symptoms for 7 days and was admitted with acute respiratory failure requiring mechanical ventilation. She progressed with hemodynamic instability responsive to vasoactive drugs. Antibiotic therapy and support measures were introduced, showing progressive hemodynamics and respiratory improvement, however with persistent fever and increased inflammatory markers. During the hospitalization, she developed bilateral non-purulent conjunctivitis, hand and feet desquamation, strawberry tongue, and cervical adenopathy, and was diagnosed with Kawasaki disease. She was prescribed intravenous immunoglobulin and, due to the refractory clinical conditions, corticosteroid therapy was added; 24 hours later, the patient was afebrile. No coronary changes were found. A full viral panel including COVID-19 C-reactive protein and serology could only isolate the Influenza B virus. During the hospitalization, she was diagnosed with pulmonary thromboembolism; coagulopathies were investigated, and she was diagnosed with heterozygous factor V Leiden mutation. There is a potential association between Kawasaki disease and infection with Influenza B or with other viruses such as coronavirus. Therefore, this association should be considered in pediatric patients, adolescents included, with prolonged febrile conditions.

Apresentação de um caso de infecção por Influenza B e doença de Kawasaki em adolescente ocorrido durante a pandemia da COVID-19. Adolescente asmática evoluiu com febre e síndrome gripal por 7 dias e deu entrada com quadro de insuficiência respiratória aguda, necessitando de intubação orotraqueal. Evoluiu também com instabilidade hemodinâmica respondedora ao uso de droga vasoativa. Foram introduzidas antibioticoterapia e medidas de suporte. Apresentou melhora hemodinâmica e respiratória progressiva, porém mantinha febre e alteração de provas inflamatórias. Durante internação, evoluiu com conjuntivite não purulenta bilateral, descamação de mão e pés, língua em framboesa e linfonodomegalia cervical, recebendo diagnóstico de doença de Kawasaki. Recebeu gamaglobulina e, por conta de quadro clínico refratário, foi administrado também corticoide, evoluindo afebril 24 horas após. Não apresentou alterações coronarianas. O único agente isolado foi Influenza B, mesmo realizando painel viral e investigação para COVID-19 com reação em cadeia da polimerase e sorologia. Durante internação, apresentou tromboembolismo pulmonar, e, em investigação de coagulopatias, foi diagnosticada com mutação em heterozigose de fator V de Leiden. Há uma potencial associação entre doença de Kawasaki e infecção por Influenza B ou outros vírus, como o coronavírus e, por isso, esses diagnósticos devem ser investigados nos pacientes pediátricos, incluindo adolescentes, com quadros febris prolongados.

The Heart of Pediatric Patients with COVID-19: New Insights from a Systematic Echocardiographic Study in a Tertiary Hospital in Brazil. / O Coração de Pacientes Pediátricos com COVID-19: Novos Insights a Partir de um Estudo Ecocardiográfico Sistemático em um Hospital Terciário no Brasil.

BACKGROUND: COVID-19 pandemic represents a huge burden to the health system in the world. Although pediatric COVID-19 patients have been relatively spared compared with adults, recent reports showed an increasing number of critically ill patients with multisystemic inflammatory syndrome in children (MIS-c), with marked cardiovascular impairment. Nevertheless, little is known about the relationship between cardiac abnormalities and inflammatory and coagulation biomarkers. OBJECTIVES: to investigate echocardiographic abnormalities in pediatric patients with COVID-19 admitted to tertiary hospital. METHODS: this was a retrospective longitudinal study, based on the review of medical records and echocardiograms of patients (0-19 years) admitted to a tertiary hospital between March 30 and June 30, 2020. For statistical analysis, the significance level was set at 5% (p < 0.05). RESULTS: Forty-eight patients were enrolled, 73% with preexisting diseases, 20 (41.7%) with MIS-c. Median age was 7.5 (0-18.6) years; 27 (56.2%) were male. Median duration of hospitalization was 15.4 (2-92) days and seven (14.6%) patients died. A total of 70 echocardiograms were performed; 66.7% patients were scanned only once and 33.3% multiple times. Twenty-three (48%) patients showed echocardiographic abnormalities: eight (16.6%) left ventricle (LV) systolic dysfunction, six (12.5%) right ventricle (RV) systolic dysfunction and 12 (25%) coronary dilatation (Z-score>+2.5). Echocardiographic abnormalities were significantly associated with MIS-c, admission to the pediatric intensive care unit, multiple organ dysfunction, ventilatory/vasoactive support, and death (p<0.05). Significantly higher d-dimer (ng/mL) levels were detected in patients with LV dysfunction [16733(4157-115668) vs. 2406.5(190-95040)], RV dysfunction [25769(3422-115668) vs. 2803.5(190-95040)] and coronary artery dilation [9652.5(921-115668) vs. 2724(190- 95040)] (p<0.05). CONCLUSION: Echocardiographic abnormalities in COVID-19 pediatric patients were frequent and associated with worse clinical outcomes. Exacerbation of the inflammation and coagulation pathways may play an important role in cardiovascular injury in those patients.

FUNDAMENTO: A pandemia da COVID-19 representa uma enorme carga para o sistema de saúde do mundo. Apesar de pacientes pediátricos terem sido relativamente poupados em comparação a adultos, estudos recentes mostraram um número crescente de pacientes críticos com Síndrome Inflamatória Multisistêmica Pediátrica (SIM-P) com disfunção cardiovascular importante. No entanto, pouco se conhece a respeito da relação entre anormalidades cardíacas e biomarcadores inflamatórios e de coagulação. OBJETIVOS: Investigar anormalidades ecocardiográficas em pacientes pediátricos com COVID-19 admitidos em um hospital terciário. MÉTODOS: Este foi um estudo longitudinal retrospectivo, baseado na revisão de prontuários médicos e ecocardiogramas de pacientes (0-19 anos) admitidos em um hospital terciário entre 30 de março e 30 de junho de 2020. Para a análise estatística, o nível de significância foi estabelecido em 5% (p<0,05). RESULTADOS: Foram incluídos 48 pacientes, 73% com doenças pré-existentes, 20 (41,7%) com SIM-P. A idade mediana foi 7,5 (0-18,6) anos; 27 (56,2%) eram do sexo masculino. A duração mediana de internação foi 15,4 (2-92) dias e sete (14,6%) pacientes morreram. Um total de 70 ecocardiografias foram realizadas, 66,7% submeteram-se ao exame somente uma vez, e 33,3% várias vezes. Vinte e três (48%) pacientes apresentaram anormalidades no ecocardiograma: oito (16.6%) disfunção sistólica do ventrículo esquerdo, seis (12.5%) disfunção sistólica do ventrículo direito, e 12 (25%) dilatação da artéria coronária (Z-score>+2,5). Anormalidades ecocardiográficas foram significativamente associadas com SIM-P, admissão na unidade de terapia intensiva pediátrica, suporte ventilatório/vasoativo, e morte ( p <0,05). Níveis significativamente mais altos de d-dímero (ng/mL) foram detectados em pacientes com disfunção ventricular esquerda [16733(4157-115668) vs. 2406.5(190-95040)], disfunção ventricular direita [25769(3422-115668) vs. 2803.5(190-95040)] e dilatação da artéria coronária [9652.5(921-115668) vs. 2724(190- 95040)] (p<0,05). CONCLUSÃO: Anormalidades ecocardiográficas eram frequentes nos pacientes pediátricos com COVID-19 e associadas com piores desfechos clínicos. Exacerbação das vias de inflamação e coagulação pode exercer um importante papel na lesão cardiovascular nesses pacientes.

An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C.

BACKGROUND: COVID-19 in children is usually mild or asymptomatic, but severe and fatal paediatric cases have been described. The pathology of COVID-19 in children is not known; the proposed pathogenesis for severe cases includes immune-mediated mechanisms or the direct effect of SARS-CoV-2 on tissues. We describe the autopsy findings in five cases of paediatric COVID-19 and provide mechanistic insight into the mechanisms involved in the pathogenesis of the disease. METHODS: Children and adolescents who died with COVID-19 between March 18 and August 15, 2020 were autopsied with a minimally invasive method. Tissue samples from all vital organs were analysed by histology, electron microscopy (EM), reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). FINDINGS: Five patients were included, one male and four female, aged 7 months to 15 years. Two patients had severe diseases before SARS-CoV-2 infection: adrenal carcinoma and Edwards syndrome. Three patients were previously healthy and had multisystem inflammatory syndrome in children (MIS-C) with distinct clinical presentations: myocarditis, colitis, and acute encephalopathy with status epilepticus. Autopsy findings varied amongst patients and included mild to severe COVID-19 pneumonia, pulmonary microthrombosis, cerebral oedema with reactive gliosis, myocarditis, intestinal inflammation, and haemophagocytosis. SARS-CoV-2 was detected in all patients in lungs, heart and kidneys by at least one method (RT-PCR, IHC or EM), and in endothelial cells from heart and brain in two patients with MIS-C (IHC). In addition, we show for the first time the presence of SARS-CoV-2 in the brain tissue of a child with MIS-C with acute encephalopathy, and in the intestinal tissue of a child with acute colitis. Interpretation: SARS-CoV-2 can infect several cell and tissue types in paediatric patients, and the target organ for the clinical manifestation varies amongst individuals. Two major patterns of severe COVID-19 were observed: a primarily pulmonary disease, with severe acute respiratory disease and diffuse alveolar damage, or a multisystem inflammatory syndrome with the involvement of several organs. The presence of SARS-CoV-2 in several organs, associated with cellular ultrastructural changes, reinforces the hypothesis that a direct effect of SARS-CoV-2 on tissues is involved in the pathogenesis of MIS-C. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Bill and Melinda Gates Foundation.

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital.

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

Beyond ventilatory support: challenges in general practice and in the treatment of critically Ill children and adolescents with SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2 infection) is a new challenge for all countries, and children are predisposed to acquire this disease. Some studies have demonstrated more severe diseases in adults, but critically ill pediatric patients have been described in all ages. Pulmonary involvement is the major feature, and ventilatory support is common in critical cases. Nevertheless, other very important therapeutic approaches must be considered. In this article, we reviewed extensively all recent medical literature to point out the main clinical attitudes to support these pediatric patients during their period in respiratory support. Radiologic findings, fluid therapy, hemodynamic support, use of inotropic/vasopressors, nutritional therapy, antiviral therapy, corticosteroids, antithrombotic therapy, and immunoglobulins are analyzed to guide all professionals during hospitalization. We emphasize the importance of a multi-professional approach for adequate recovery.

Update on the diagnosis and management of COVID-19 in pediatric patients.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became a pandemic in March 2020, affecting millions of people worldwide. However, COVID-19 in pediatric patients represents 1-5% of all cases, and the risk for developing severe disease and critical illness is much lower in children with COVID-19 than in adults. Multisystem inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection. This review presents an update on the diagnostic methods for COVID-19, including reverse-transcriptase polymerase chain reaction (RT-PCR) tests, serology tests, and imaging, and summarizes the current recommendations for the management of the disease. Particular emphasis is placed on respiratory support, which includes noninvasive ventilation and invasive mechanical ventilation strategies according to lung compliance and pattern of lung injury. Pharmacological treatment, including pathogen-targeted drugs and host-directed therapies, has been addressed. The diagnostic criteria and management of MIS-C are also summarized.

Prolonged suppression of monocytic human leukocyte antigen-DR expression correlates with mortality in pediatric septic patients in a pediatric tertiary Intensive Care Unit.

INTRODUCTION: Immunoparalysis is a syndrome with no clinical symptoms that occurs in some septic patients. Monocytic human leukocyte antigen-DR (mHLA-DR) expression has been used to identify patients in immunoparalysis and prolonged periods of reduced mHLA-DR expression have been correlated with a poor prognosis in sepsis. However, there is a lack of studies investigating mHLA-DR expression in pediatric septic patients. AIM: To determine if mHLA-DR expression correlates with mortality in pediatric septic patients using the QuantiBRITE Anti HLA-DR/Anti-Monocyte,a Bechton Dickinson novel reagent that standardizes flow cytometry values. METHODS: We determined mHLA-DR expression in 30 patients with severe sepsis or septic shock admitted to the pediatric intensive care unit at Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil, between January 2013 and February 2015. mHLA-DR expression was quantified between days 3 to 5 and 5 to 7 after the onset of sepsis and the ΔmHLA-DR (mHLA-DR2 - mHLA-DR1) was calculated. We also measured mHLA-DR levels in 21 healthy control patients. RESULTS: Mean mHLA-DR expression was significantly lower in septic patients than in controls (P = .0001). Mortality was 46% in patients with negative ΔHLA-DR or <1000 mAb/cell and 7% in patients with positive ΔHLA-DR or >1000 mAb/cell. Mean ΔmHLA-DR levels were significantly different between survivors and non-survivors (P = .023). CONCLUSION: ΔHLA-DR correlates with mortality in pediatric patients with septic shock or severe sepsis. This is the first study to have used the QuantiBRITE Anti HLA-DR/Anti-Monocyte reagent to quantify monocyte HLA-DR expression in pediatric septic patients.

O coração de pacientes pediátricos com COVID-19: novos insights a partir de um estudo ecocardiográfico sistemático em um Hospital Terciário no Brasil / The heart of pediatric patients with COVID-19: new insights from a systematic chocardiographic study in a Tertiary Hospital in Brazil

Resumo Fundamento A pandemia da COVID-19 representa uma enorme carga para o sistema de saúde do mundo. Apesar de pacientes pediátricos terem sido relativamente poupados em comparação a adultos, estudos recentes mostraram um número crescente de pacientes críticos com Síndrome Inflamatória Multisistêmica Pediátrica (SIM-P) com disfunção cardiovascular importante. No entanto, pouco se conhece a respeito da relação entre anormalidades cardíacas e biomarcadores inflamatórios e de coagulação. Objetivos Investigar anormalidades ecocardiográficas em pacientes pediátricos com COVID-19 admitidos em um hospital terciário. Métodos Este foi um estudo longitudinal retrospectivo, baseado na revisão de prontuários médicos e ecocardiogramas de pacientes (0-19 anos) admitidos em um hospital terciário entre 30 de março e 30 de junho de 2020. Para a análise estatística, o nível de significância foi estabelecido em 5% (p<0,05). Resultados Foram incluídos 48 pacientes, 73% com doenças pré-existentes, 20 (41,7%) com SIM-P. A idade mediana foi 7,5 (0-18,6) anos; 27 (56,2%) eram do sexo masculino. A duração mediana de internação foi 15,4 (2-92) dias e sete (14,6%) pacientes morreram. Um total de 70 ecocardiografias foram realizadas, 66,7% submeteram-se ao exame somente uma vez, e 33,3% várias vezes. Vinte e três (48%) pacientes apresentaram anormalidades no ecocardiograma: oito (16.6%) disfunção sistólica do ventrículo esquerdo, seis (12.5%) disfunção sistólica do ventrículo direito, e 12 (25%) dilatação da artéria coronária (Z-score>+2,5). Anormalidades ecocardiográficas foram significativamente associadas com SIM-P, admissão na unidade de terapia intensiva pediátrica, suporte ventilatório/vasoativo, e morte ( p <0,05). Níveis significativamente mais altos de d-dímero (ng/mL) foram detectados em pacientes com disfunção ventricular esquerda [16733(4157-115668) vs. 2406.5(190-95040)], disfunção ventricular direita [25769(3422-115668) vs. 2803.5(190-95040)] e dilatação da artéria coronária [9652.5(921-115668) vs. 2724(190- 95040)] (p<0,05). Conclusão Anormalidades ecocardiográficas eram frequentes nos pacientes pediátricos com COVID-19 e associadas com piores desfechos clínicos. Exacerbação das vias de inflamação e coagulação pode exercer um importante papel na lesão cardiovascular nesses pacientes.

Abstract Background COVID-19 pandemic represents a huge burden to the health system in the world. Although pediatric COVID-19 patients have been relatively spared compared with adults, recent reports showed an increasing number of critically ill patients with multisystemic inflammatory syndrome in children (MIS-c), with marked cardiovascular impairment. Nevertheless, little is known about the relationship between cardiac abnormalities and inflammatory and coagulation biomarkers. Objectives to investigate echocardiographic abnormalities in pediatric patients with COVID-19 admitted to tertiary hospital. Methods this was a retrospective longitudinal study, based on the review of medical records and echocardiograms of patients (0-19 years) admitted to a tertiary hospital between March 30 and June 30, 2020. For statistical analysis, the significance level was set at 5% (p < 0.05). Results Forty-eight patients were enrolled, 73% with preexisting diseases, 20 (41.7%) with MIS-c. Median age was 7.5 (0-18.6) years; 27 (56.2%) were male. Median duration of hospitalization was 15.4 (2-92) days and seven (14.6%) patients died. A total of 70 echocardiograms were performed; 66.7% patients were scanned only once and 33.3% multiple times. Twenty-three (48%) patients showed echocardiographic abnormalities: eight (16.6%) left ventricle (LV) systolic dysfunction, six (12.5%) right ventricle (RV) systolic dysfunction and 12 (25%) coronary dilatation (Z-score>+2.5). Echocardiographic abnormalities were significantly associated with MIS-c, admission to the pediatric intensive care unit, multiple organ dysfunction, ventilatory/vasoactive support, and death (p<0.05). Significantly higher d-dimer (ng/mL) levels were detected in patients with LV dysfunction [16733(4157-115668) vs. 2406.5(190-95040)], RV dysfunction [25769(3422-115668) vs. 2803.5(190-95040)] and coronary artery dilation [9652.5(921-115668) vs. 2724(190- 95040)] (p<0.05). Conclusion Echocardiographic abnormalities in COVID-19 pediatric patients were frequent and associated with worse clinical outcomes. Exacerbation of the inflammation and coagulation pathways may play an important role in cardiovascular injury in those patients.

An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C

Background: COVID-19 in children is usually mild or asymptomatic, but severe and fatal paediatric cases have been described. The pathology of COVID-19 in children is not known; the proposed pathogenesis for severe cases includes immune-mediated mechanisms or the direct effect of SARS-CoV-2 on tissues. We describe the autopsy findings in five cases of paediatric COVID-19 and provide mechanistic insight into the mechanisms involved in the pathogenesis of the disease. Methods: Children and adolescents who died with COVID-19 between March 18 and August 15, 2020 were autopsied with a minimally invasive method. Tissue samples from all vital organs were analysed by histology, electron microscopy (EM), reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Findings: Five patients were included, one male and four female, aged 7 months to 15 years. Two patients had severe diseases before SARS-CoV-2 infection: adrenal carcinoma and Edwards syndrome. Three patients were previously healthy and had multisystem inflammatory syndrome in children (MIS-C) with distinct clinical presentations: myocarditis, colitis, and acute encephalopathy with status epilepticus. Autopsy findings varied amongst patients and included mild to severe COVID-19 pneumonia, pulmonary microthrombosis, cerebral oedema with reactive gliosis, myocarditis, intestinal inflammation, and haemophagocytosis. SARSCoV- 2 was detected in all patients in lungs, heart and kidneys by at least one method (RT-PCR, IHC or EM), and in endothelial cells from heart and brain in two patients with MIS-C (IHC). In addition, we show for the first time the presence of SARS-CoV-2 in the brain tissue of a child with MIS-C with acute encephalopathy, and in the intestinal tissue of a child with acute colitis. Interpretation: SARS-CoV-2 can infect several cell and tissue types in paediatric patients, and the target organ for the...(AU)

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

Beyond ventilatory support: challenges in general practice and in the treatment of critically Ill children and adolescents with SARS-CoV-2 infection

SUMMARY Severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2 infection) is a new challenge for all countries, and children are predisposed to acquire this disease. Some studies have demonstrated more severe diseases in adults, but critically ill pediatric patients have been described in all ages. Pulmonary involvement is the major feature, and ventilatory support is common in critical cases. Nevertheless, other very important therapeutic approaches must be considered. In this article, we reviewed extensively all recent medical literature to point out the main clinical attitudes to support these pediatric patients during their period in respiratory support. Radiologic findings, fluid therapy, hemodynamic support, use of inotropic/vasopressors, nutritional therapy, antiviral therapy, corticosteroids, antithrombotic therapy, and immunoglobulins are analyzed to guide all professionals during hospitalization. We emphasize the importance of a multi-professional approach for adequate recovery.

RESUMO A síndrome respiratória aguda grave (SRAG) pelo novo coronavirus (SARS-CoV-2) é um novo desafio para todos os países e crianças estão predispostas a adquirir a doença. Alguns estudos demonstraram quadros mais graves em adultos, mas crianças criticamente doentes foram descritas em todas as idades. O envolvimento pulmonar é a principal característica e a necessidade de suporte ventilatório é comum nos casos mais graves. Entretanto, outras abordagens terapêuticas importantes devem ser consideradas. Nesse artigo revisamos extensamente a literature médica até o momento a fim de citar os principais recursos terapêuticos para o manejo dos pacientes pediátricos durante o período de suporte ventilatório. Achados radiológicos, terapia fluídica, terapia antiviral, o uso de corticosteroides, terapia antitrombótica e o uso de imunoglobulinas foram analisados a fim de guiar os profissionais durante o período de hospitalização desses pacientes. Nós reforçamos a importância de uma abordagem multiprofissional para recuperação adequada.

Update on the diagnosis and management of COVID-19 in pediatric patients

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became a pandemic in March 2020, affecting millions of people worldwide. However, COVID-19 in pediatric patients represents 1-5% of all cases, and the risk for developing severe disease and critical illness is much lower in children with COVID-19 than in adults. Multisystem inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection. This review presents an update on the diagnostic methods for COVID-19, including reverse-transcriptase polymerase chain reaction (RT-PCR) tests, serology tests, and imaging, and summarizes the current recommendations for the management of the disease. Particular emphasis is placed on respiratory support, which includes noninvasive ventilation and invasive mechanical ventilation strategies according to lung compliance and pattern of lung injury. Pharmacological treatment, including pathogen-targeted drugs and host-directed therapies, has been addressed. The diagnostic criteria and management of MIS-C are also summarized.

Fulminant myocarditis associated with the H1N1 influenza virus: case report and literature review.

A case of fulminant myocarditis associated with the H1N1 influenza virus. This case report describes the patient's clinical course and emphasizes the importance of bedside echocardiography as an aid in the early diagnosis and management of children with severe myocardial dysfunction. It also discusses aspects relevant to the treatment and prognosis of fulminant myocarditis. The patient was a female, 4 years and 8 months old, previously healthy and with a history of flu symptoms in the past two weeks. The patient was admitted to the emergency room with signs of hemodynamic instability, requiring ventilatory support and vasoactive drugs. The laboratory tests, chest X-ray and echocardiogram suggested the presence of myocarditis. The test for H1N1 in nasopharyngeal secretions was positive. The patient evolved to refractory cardiogenic shock despite the clinical measures applied and died 48 hours after admission to the intensive care unit. The H1N1 influenza virus is an etiological agent associated with acute myocarditis, but there are few reported cases of fulminant myocarditis caused by the H1N1 virus. The identification of signs and symptoms suggestive of fulminant progression should be immediate, and bedside echocardiography is a useful tool for the early detection of myocardial dysfunction and for therapeutic guidance. The use of immunosuppressive therapy and antiviral therapy in acute myocarditis of viral etiology is controversial; hence,the treatment is based on hemodynamic and ventilatory support. The use of hemodynamic support by extracorporeal membrane oxygenation emerges as a promising treatment.

Miocardite fulminante associada ao vírus influenza H1N1: relato de caso e revisão de literatura / Fulminant myocarditis associated with the H1N1 influenza virus: case report and literature review

Caso de miocardite fulminante associada ao vírus influenza H1N1, em que foi descrita a evolução clínica do paciente e enfatizada a importância do ecocardiograma à beira do leito como auxílio no diagnóstico precoce e manejo de crianças com disfunção miocárdica grave, além de terem sido discutidos aspectos relevantes relacionados à terapêutica e ao prognóstico da miocardite fulminante. Trata-se de paciente do sexo feminino, 4 anos e 8 meses, previamente hígida, com história de quadro gripal há 2 semanas. Admitida no pronto-socorro com sinais de instabilidade hemodinâmica, necessitando de suporte ventilatório e drogas vasoativas. Exames laboratoriais, radiografia de tórax e ecocardiograma sugestivos de miocardite. Pesquisa positiva para H1N1 em secreção de nasofaringe. Evoluiu com choque cardiogênico refratário a despeito das medidas clínicas, indo a óbito em 48 horas após admissão na unidade de terapia intensiva. O vírus influenza H1N1 é agente etiológico associado a quadros de miocardite aguda, porém poucos são os casos relatados de miocardite fulminante pelo vírus H1N1. A identificação de sinais e sintomas sugestivos de evolução fulminante deve ser imediata e o ecocardiograma à beira do leito é uma ferramenta útil para detecção precoce de disfunção miocárdica e orientação terapêutica. O uso de terapia imunossupressora, em casos de miocardite fulminante de etiologia viral, é controverso, bem como o de terapia antiviral, de tal forma que o tratamento baseia-se em suporte hemodinâmico e ventilatório. O uso de suporte hemodinâmico, por meio de oxigenação por membrana extracorpórea, aparece como terapia promissora.

A case of fulminant myocarditis associated with the H1N1 influenza virus. This case report describes the patient's clinical course and emphasizes the importance of bedside echocardiography as an aid in the early diagnosis and management of children with severe myocardial dysfunction. It also discusses aspects relevant to the treatment and prognosis of fulminant myocarditis. The patient was a female, 4 years and 8 months old, previously healthy and with a history of flu symptoms in the past two weeks. The patient was admitted to the emergency room with signs of hemodynamic instability, requiring ventilatory support and vasoactive drugs. The laboratory tests, chest X-ray and echocardiogram suggested the presence of myocarditis. The test for H1N1 in nasopharyngeal secretions was positive. The patient evolved to refractory cardiogenic shock despite the clinical measures applied and died 48 hours after admission to the intensive care unit. The H1N1 influenza virus is an etiological agent associated with acute myocarditis, but there are few reported cases of fulminant myocarditis caused by the H1N1 virus. The identification of signs and symptoms suggestive of fulminant progression should be immediate, and bedside echocardiography is a useful tool for the early detection of myocardial dysfunction and for therapeutic guidance. The use of immunosuppressive therapy and antiviral therapy in acute myocarditis of viral etiology is controversial; hence, the treatment is based on hemodynamic and ventilatory support. The use of hemodynamic support by extracorporeal membrane oxygenation emerges as a promising treatment.