Biomarcadores da tempestade de citocinas como sinalizadores de casos graves e fatais da COVID-19: revisão sistemática e metanálise
Data
2024-02-08
Orientadores
Trevisani, Virgínia Fernandes Moça 
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Contexto: Em março de 2020, a Organização Mundial de Saúde declarou uma pandemia devido à doença causada pelo novo coronavírus, a COVID-19. Um subgrupo de pacientes com COVID-19 pode ter uma síndrome inflamatória sistêmica, denominada síndrome da tempestade de citocinas, com amplificação da resposta imune e desregulação dos mecanismos supressores da cascata inflamatória. Objetivos: Identificar biomarcadores da síndrome da tempestade de citocinas associados a casos graves e fatais da COVID-19. Métodos: Uma busca com descritores e sinônimos padronizados foi realizada em 28 de novembro de 2020 no MEDLINE, EMBASE, Biblioteca Cochrane Central, Clinical-Trials.gov, LILACS e The World Health Organization International Clinical Trials Registry Platform, para identificar estudos de interesse. Pesquisas na literatura cinzenta e técnicas de snowballing também foram utilizadas para localizar trabalhos ainda não publicados e citações relacionadas. Dois revisores examinaram independentemente os títulos e resumos recuperados, selecionaram estudos elegíveis para inclusão, extraíram dados dos estudos incluídos e avaliaram o risco de viés usando a Escala de Newcastle-Ottawa modificada. Os estudos elegíveis foram aqueles que incluíram níveis séricos de interleucina-6 e outros parâmetros laboratoriais de pacientes admitidos para internação hospitalar por COVID-19. Os valores de interleucina-6, ferritina, hemoglobina, leucócitos, neutrófilos, linfócitos, plaquetas, proteína C reativa, procalcitonina, desidrogenase láctica, aspartato aminotransferase, creatinina e dímero-D foram extraídos dos estudos. Avaliou-se a certeza da evidência utilizando a abordagem GRADE para alguns desfechos priorizados. Metanálises de efeito randômico foram realizadas usando os dados laboratoriais, para estimar as diferenças de médias com intervalo de confiança de 95%. O software R foi utilizado para os cálculos. Resultados: A busca nas bases de dados resultou em 9.620 registros; 40 estudos (contendo um total de 9.542 pacientes) foram incluídos na análise final. Vinte e um estudos (n = 4.313 pacientes) avaliaram dados laboratoriais associados à gravidade da COVID-19; dezoito estudos (n = 4.681 pacientes) avaliaram dados laboratoriais associados ao desfecho de mortalidade, e um estudo (n = 548 pacientes) avaliou biomarcadores associados a casos graves e fatais da COVID-19. Níveis elevados de interleucina-6, ferritina, dímero-D, aspartato aminotransferase, proteína C reativa, desidrogenase láctica, procalcitonina e creatinina, além de linfopenia, trombocitopenia, leucocitose e neutrofilia foram associados a casos graves e fatais da COVID-19. Conclusões: Esta revisão aponta que os níveis séricos de interleucina-6, ferritina, leucócitos, neutrófilos, linfócitos, plaquetas, proteína C reativa, procalcitonina, desidrogenase láctica, aspartato aminotransferase, creatinina e dímero-D são importantes biomarcadores da síndrome da tempestade de citocinas na COVID-19. A determinação precoce de níveis elevados de interleucina-6 e ferritina séricas em pacientes internados por COVID-19 deve ser considerada como sinal de alerta de hiperinflamação sistêmica e mau prognóstico.
Background: In March 2020, the World Health Organization declared a pandemic due to the disease caused by the new coronavirus, COVID-19. A subset of COVID-19 patients may experience cytokine storm syndrome, an inflammatory condition that amplifies the immune response and disrupts mechanisms that regulate inflammation. Objective: To identify biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods: A search with standardized descriptors and synonyms was performed on November 28th, 2020, of the MEDLINE, EMBASE, The Cochrane Library, Clinical-Trials.gov, LILACS, and The World Health Organization International Clinical Trials Registry Platform to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. The studies that were considered eligible were those that included laboratory parameters such as serum interleukin-6 levels, from patients who have been diagnosed with COVID-19. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, cretinine, and D-dimer, were extracted from the studies. We rated the certainty of evidence using the GRADE approach for some prioritized outcomes. Meta-analyses of random effect were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. The R software was used for all calculations. Results: The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313 patients) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681 patients) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed biomarkers related to severe and fatal COVID-19 cases. Elevated levels of certain biomarkers, including interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-reactive protein, procalcitonin, lactate dehydrogenase, creatinine, neutrophils, and leucocytes, and decreased levels of lymphocytes and platelets were found to be associated with severe and fatal COVID-19 cases. Conclusions: This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-reactive protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of the cytokine storm syndrome. Early detection of high serum interleukin-6 and hyperferritinemia in hospitalized COVID-19 patients is crucial. These levels may signal systemic hyperinflammation and predict a poor prognosis.
Background: In March 2020, the World Health Organization declared a pandemic due to the disease caused by the new coronavirus, COVID-19. A subset of COVID-19 patients may experience cytokine storm syndrome, an inflammatory condition that amplifies the immune response and disrupts mechanisms that regulate inflammation. Objective: To identify biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods: A search with standardized descriptors and synonyms was performed on November 28th, 2020, of the MEDLINE, EMBASE, The Cochrane Library, Clinical-Trials.gov, LILACS, and The World Health Organization International Clinical Trials Registry Platform to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. The studies that were considered eligible were those that included laboratory parameters such as serum interleukin-6 levels, from patients who have been diagnosed with COVID-19. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, cretinine, and D-dimer, were extracted from the studies. We rated the certainty of evidence using the GRADE approach for some prioritized outcomes. Meta-analyses of random effect were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. The R software was used for all calculations. Results: The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313 patients) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681 patients) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed biomarkers related to severe and fatal COVID-19 cases. Elevated levels of certain biomarkers, including interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-reactive protein, procalcitonin, lactate dehydrogenase, creatinine, neutrophils, and leucocytes, and decreased levels of lymphocytes and platelets were found to be associated with severe and fatal COVID-19 cases. Conclusions: This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-reactive protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of the cytokine storm syndrome. Early detection of high serum interleukin-6 and hyperferritinemia in hospitalized COVID-19 patients is crucial. These levels may signal systemic hyperinflammation and predict a poor prognosis.
Descrição
Citação
MELO, Ana Karla Guedes de. Biomarcadores da tempestade de citocinas como sinalizadores de casos graves e fatais da COVID-19: revisão sistemática e metanálise. 2024. 135 f. Tese (Doutorado em Saúde Baseada em Evidências) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2024.