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Abstract(s)
Introdução: O curso clínico da infeção por SARS-CoV-2 na população pediátrica é
geralmente benigno, com infeção assintomática ou doença ligeira na esmagadora
maioria das crianças. Porém, em abril 2020 surgiram relatos de casos de um estado
hiperinflamatório sistémico tardio em crianças previamente infetadas com SARS-CoV2. Esta entidade veio a ser denominada pela Organização Mundial de Saúde como
Síndrome Inflamatória Multissistémica em Crianças associada a COVID-19 (MIS-C). A
MIS-C constitui uma rara, mas grave complicação, que geralmente ocorre até 6 semanas
após a infeção por SARS-CoV-2, contudo, não existe ainda uma abordagem diagnóstica
e terapêutica consensual entre as autoridades internacionais de saúde.
Objetivos: A presente revisão pretende investigar e comparar, em função dos seus
principais resultados, as opções terapêuticas de primeira linha atualmente mais usadas:
imunoglobulina, glucocorticoides, ou a sua combinação.
Materiais e Métodos: Esta revisão sistemática seguiu as recomendações PRISMA 2020.
Foi realizada uma pesquisa inicial de bases de dados até 1 de dezembro de 2022, que
incluiu EBSCOhost, Cochrane e PubMed. Os algoritmos utilizados foram construídos
estrategicamente com recurso a termos MeSH. Consideraram-se elegíveis ensaios
clínicos randomizados, estudos de caso-controlo e de coorte, cuja amostra incluísse
pacientes diagnosticados com MIS-C de acordo com os critérios da Organização Mundial
de Saúde, Centro de Controle e Prevenção de Doenças e Royal College of Pediatrics and
Child Health e tratados com os fármacos em questão. Após uma primeira fase de seleção
com base em título e resumo de cada um dos resultados da pesquisa, foram lidos os
restantes artigos na íntegra e excluídos ou incluídos consoante a sua correspondência
aos critérios de elegibilidade. A qualidade de evidência e risco de viés dos estudos
incluídos foram avaliadas através da escala Newcastle Ottawa e a ferramenta ROBINS-I,
respetivamente. Por fim, os resultados de cada artigo foram sintetizados em tabelas, de
forma a comparar as diferenças significativas que se revelaram entre cada grupo de
tratamento.
Resultados: De 445 artigos científicos encontrados, foram incluídos dez estudos de
coorte, com uma amostra total de 1316 pacientes. A maioria dos estudos foram
classificados como sendo de “boa qualidade” na escala de Newcastle Ottawa. As medidas
de outcome analisadas foram a normalização da temperatura e outros parâmetros
inflamatórios, a taxa de falência de tratamento com necessidade de recurso a uma segunda linha terapêutica, a evolução da função cardiovascular e respiratória, assim
como a duração de internamento. A terapêutica de primeira linha com imunoglobulina
isolada foi comparada em sete dos dez estudos com um grupo tratado com a associação
de imunoglobulina e glucocorticoides e noutros três estudos com glucocorticoides
isolados. Apenas um estudo fez a comparação entre o tratamento com apenas
glucocorticoides e o tratamento com a associação de imunoglobulina e glucocorticoides.
Nenhum estudo reportou resultados significativamente melhores nos pacientes tratados
com imunoglobulina intravenosa isoladamente. Pelo contrário, cinco artigos concluíram
que o tratamento combinado, quando comparado com imunoglobulina isolada resultou
numa mais célere recuperação da função cardiovascular e/ou normalização
significativamente mais rápida da febre e outros parâmetros inflamatórios. Também os
três estudos que compararam a opção por imunoglobulina isolada com a opção por
glucocorticoides isolados demonstraram vantagens significativas na opção por
glucocorticoides.
Conclusão: A maioria dos artigos analisados sugere que o tratamento em primeira linha
da MIS-C com imunoglobulina isolada tem resultados significativamente inferiores que
o tratamento com glucocorticoides tanto associados a imunoglobulina, como em
monoterapia. No entanto, importa sublinhar o facto de todos os estudos incluídos serem
de caráter observacional não randomizados, pelo que, urge a realização de ensaios
clínicos randomizados que permitiam tirar conclusões mais definitivas.
Introduction: The clinical course of SARS-CoV-2 infection in the pediatric population was initially thought to be benign, with asymptomatic infection or mild disease in the overwhelming majority of children. However, in April 2020 case reports emerged, describing a late systemic hyperinflammatory state in children previously infected with SARS-CoV-2. This entity came to be named by the World Health Organization as Multisystemic Inflammatory Syndrome in Children associated with COVID-19 (MIS-C). MIS-C is a rare but serious complication, which usually occurs up to 6 weeks after SARSCoV-2 infection, however, there is still no consensus on the best diagnostic and therapeutic approach among international health authorities. Objectives: This review intends to investigate and compare the results of the first line treatment options that are currently most used: immunoglobulin, glucocorticoids, or their combination. Materials and Methods: This systematic review followed the PRISMA 2020 guidelines. An initial search was performed up to December 1st, 2022, on databases including EBSCOhost, Cochrane, and PubMed. The algorithms used were strategically constructed using MeSH terms. Randomized clinical trials, case-control and cohort studies, whose sample included patients diagnosed with MIS-C according to the World Health Organization, Centers for Disease Control and Prevention or Royal College of Pediatrics and Child Health criteria and treated with the drugs in question, were considered eligible. After a first phase of selection based on the title and abstract of each record, the remaining articles were read in full and excluded or included according to their correspondence to the eligibility criteria. The quality of evidence and risk of bias of the included studies were assessed using the Newcastle Ottawa scale and the ROBINS-I tool, respectively. Finally, the results of each article were summarized in tables allowing for a better comparison of significant differences that were found between each treatment group. Results: Of 445 search results, ten cohort studies were included, with a total sample of 1316 patients. Most studies were rated as being of “good quality” on the Newcastle Ottawa scale. The outcome measures analysed were time to resolution of fever and other inflammatory parameters, rate of treatment failure requiring a second line of therapy, evolution of cardiovascular and respiratory function, as well as the length of hospital stay. First-line therapy with immunoglobulin alone was compared in seven of the ten studies against treatment with a combination of immunoglobulin and glucocorticoids and in another three studies against treatment with glucocorticoids alone. Only one study compared treatment with only glucocorticoids to treatment with an association of immunoglobulin and glucocorticoids. No studies reported significantly better outcomes in patients treated with intravenous immunoglobulin alone. On the contrary, five articles concluded that the combined treatment, when compared with isolated immunoglobulin, resulted in a faster recovery of cardiovascular function and/or a significantly faster normalization of fever and other inflammatory parameters. Similarly, the three studies that compared the option of isolated immunoglobulin against isolated glucocorticoids showed significant advantages in choosing the latter one. Conclusion: Most of the analysed articles suggest that first-line treatment of MIS-C with isolated immunoglobulin has significantly inferior outcomes when compared to the treatment with glucocorticoids both associated with immunoglobulin and in monotherapy. However, it is important to note that all the studies included were observational and non-randomized, making it urgent for randomized clinical trials to be conducted and published, which will allow more definitive conclusions to be drawn.
Introduction: The clinical course of SARS-CoV-2 infection in the pediatric population was initially thought to be benign, with asymptomatic infection or mild disease in the overwhelming majority of children. However, in April 2020 case reports emerged, describing a late systemic hyperinflammatory state in children previously infected with SARS-CoV-2. This entity came to be named by the World Health Organization as Multisystemic Inflammatory Syndrome in Children associated with COVID-19 (MIS-C). MIS-C is a rare but serious complication, which usually occurs up to 6 weeks after SARSCoV-2 infection, however, there is still no consensus on the best diagnostic and therapeutic approach among international health authorities. Objectives: This review intends to investigate and compare the results of the first line treatment options that are currently most used: immunoglobulin, glucocorticoids, or their combination. Materials and Methods: This systematic review followed the PRISMA 2020 guidelines. An initial search was performed up to December 1st, 2022, on databases including EBSCOhost, Cochrane, and PubMed. The algorithms used were strategically constructed using MeSH terms. Randomized clinical trials, case-control and cohort studies, whose sample included patients diagnosed with MIS-C according to the World Health Organization, Centers for Disease Control and Prevention or Royal College of Pediatrics and Child Health criteria and treated with the drugs in question, were considered eligible. After a first phase of selection based on the title and abstract of each record, the remaining articles were read in full and excluded or included according to their correspondence to the eligibility criteria. The quality of evidence and risk of bias of the included studies were assessed using the Newcastle Ottawa scale and the ROBINS-I tool, respectively. Finally, the results of each article were summarized in tables allowing for a better comparison of significant differences that were found between each treatment group. Results: Of 445 search results, ten cohort studies were included, with a total sample of 1316 patients. Most studies were rated as being of “good quality” on the Newcastle Ottawa scale. The outcome measures analysed were time to resolution of fever and other inflammatory parameters, rate of treatment failure requiring a second line of therapy, evolution of cardiovascular and respiratory function, as well as the length of hospital stay. First-line therapy with immunoglobulin alone was compared in seven of the ten studies against treatment with a combination of immunoglobulin and glucocorticoids and in another three studies against treatment with glucocorticoids alone. Only one study compared treatment with only glucocorticoids to treatment with an association of immunoglobulin and glucocorticoids. No studies reported significantly better outcomes in patients treated with intravenous immunoglobulin alone. On the contrary, five articles concluded that the combined treatment, when compared with isolated immunoglobulin, resulted in a faster recovery of cardiovascular function and/or a significantly faster normalization of fever and other inflammatory parameters. Similarly, the three studies that compared the option of isolated immunoglobulin against isolated glucocorticoids showed significant advantages in choosing the latter one. Conclusion: Most of the analysed articles suggest that first-line treatment of MIS-C with isolated immunoglobulin has significantly inferior outcomes when compared to the treatment with glucocorticoids both associated with immunoglobulin and in monotherapy. However, it is important to note that all the studies included were observational and non-randomized, making it urgent for randomized clinical trials to be conducted and published, which will allow more definitive conclusions to be drawn.
Description
Keywords
Glucocorticoides Imunoglobulina Mis-C Sars-Cov-2 Tratamento