학술논문
An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C.
Document Type
Academic Journal
Author
Duarte-Neto AN; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.; Instituto Adolfo Lutz. Av. Dr. Arnaldo, 351, 01246-000 São Paulo, SP, Brasil.; Caldini EG; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.; Gomes-Gouvêa MS; Departamento de Gastroenterologia, LIM 07, Faculdade de Medicina da Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 500, 05403-000 São Paulo, SP, Brasil.; Kanamura CT; Instituto Adolfo Lutz. Av. Dr. Arnaldo, 351, 01246-000 São Paulo, SP, Brasil.; de Almeida Monteiro RA; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.; Ferranti JF; Instituto da Criança, Departamento de Pediatria, Faculdade de Medicina da Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 647, 05403-000 São Paulo, SP, Brasil.; Ventura AMC; Unidade de Terapia Intensiva Pediátrica, Departamento de Pediatria, Hospital Universitário da Universidade de São Paulo. Av. Prof. Lineu Prestes, 2565, 05508-000 São Paulo, SP, Brasil.; Regalio FA; Divisão de Anestesia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Av. Dr Enéas de Carvalho Aguiar, 255, 01246-000 São Paulo, SP, Brasil.; Fiorenzano DM; Instituto da Criança, Departamento de Pediatria, Faculdade de Medicina da Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 647, 05403-000 São Paulo, SP, Brasil.; Gibelli MABC; Instituto da Criança, Departamento de Pediatria, Faculdade de Medicina da Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 647, 05403-000 São Paulo, SP, Brasil.; Carvalho WB; Instituto da Criança, Departamento de Pediatria, Faculdade de Medicina da Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 647, 05403-000 São Paulo, SP, Brasil.; Leal GN; Instituto da Criança, Departamento de Pediatria, Faculdade de Medicina da Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 647, 05403-000 São Paulo, SP, Brasil.; Pinho JRR; Departamento de Gastroenterologia, LIM 07, Faculdade de Medicina da Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 500, 05403-000 São Paulo, SP, Brasil.; Delgado AF; Instituto da Criança, Departamento de Pediatria, Faculdade de Medicina da Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 647, 05403-000 São Paulo, SP, Brasil.; Carneiro-Sampaio M; Instituto da Criança, Departamento de Pediatria, Faculdade de Medicina da Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 647, 05403-000 São Paulo, SP, Brasil.; Mauad T; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.; Ferraz da Silva LF; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.; Serviço de Verificação de Óbitos da Capital, Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 250, 05403-000 São Paulo, SP, Brasil.; Saldiva PHN; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.; Dolhnikoff M; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.
Source
Publisher: The Lancet Country of Publication: England NLM ID: 101733727 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2589-5370 (Electronic) Linking ISSN: 25895370 NLM ISO Abbreviation: EClinicalMedicine Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
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.
Competing Interests: We declare no competing interests.
(© 2021 The Author(s).)
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.
Competing Interests: We declare no competing interests.
(© 2021 The Author(s).)