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An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C.
Duarte-Neto, Amaro Nunes; Caldini, Elia Garcia; Gomes-Gouvêa, Michele Soares; Kanamura, Cristina Takami; de Almeida Monteiro, Renata Aparecida; Ferranti, Juliana Ferreira; Ventura, Andrea Maria Cordeiro; Regalio, Fabiane Aliotti; Fiorenzano, Daniela Matos; Gibelli, Maria Augusta Bento Cicaroni; Carvalho, Werther Brunow de; Leal, Gabriela Nunes; Pinho, João Renato Rebello; Delgado, Artur Figueiredo; Carneiro-Sampaio, Magda; Mauad, Thais; Ferraz da Silva, Luiz Fernando; Saldiva, Paulo Hilario Nascimento; Dolhnikoff, Marisa.
  • Duarte-Neto AN; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.
  • Caldini EG; Instituto Adolfo Lutz. Av. Dr. Arnaldo, 351, 01246-000 São Paulo, SP, Brasil.
  • Gomes-Gouvêa MS; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.
  • Kanamura CT; 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.
  • de Almeida Monteiro RA; Instituto Adolfo Lutz. Av. Dr. Arnaldo, 351, 01246-000 São Paulo, SP, Brasil.
  • Ferranti JF; Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo. Av. Dr. Arnaldo, 455, 01246-903 São Paulo, SP, Brasil.
  • Ventura AMC; 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.
  • Regalio FA; 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.
  • Fiorenzano DM; 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.
  • 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; 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.
  • Delgado AF; 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.
  • 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; 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.
  • 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.
  • 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; Serviço de Verificação de Óbitos da Capital, Universidade de São Paulo. Av Dr Enéas de Carvalho Aguiar, 250, 05403-000 São Paulo, SP, Brasil.
EClinicalMedicine ; 35: 100850, 2021 May.
Article in English | MEDLINE | ID: covidwho-1201119
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.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: EClinicalMedicine Year: 2021 Document Type: Article Affiliation country: J.eclinm.2021.100850

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: EClinicalMedicine Year: 2021 Document Type: Article Affiliation country: J.eclinm.2021.100850