SARS-CoV-2 infection of the central nervous system in a 14-month-old child: A case report of a complete autopsy.

Abstract Background Neurological and other systemic complications occur in adults with severe COVID-19. Here we describe SARS-CoV-2 infection complicated by neuroinvasion in the post-mortem tissues of a child. Methods We performed a complete autopsy of a 14-month-old child who died of COVID-19 pneumonitis. Histological sections of multiple organs were stained with haematoxylin and eosin. Luxol fast blue staining for myelin and immunohistochemistry were performed in selected areas of the brain. The presence of SARS-CoV-2 was investigated by immunostaining with anti-spike protein antibody and by RT-qPCR. Findings Lesions included microthrombosis, pulmonary congestion, interstitial oedema, lymphocytic infiltrates, bronchiolar injury, collapsed alveolar spaces, cortical atrophy, and severe neuronal loss. SARS-CoV-2 staining was observed along the apical region of the choroid plexus (ChP) epithelium and in ependymal cells of the lateral ventricle, but was restricted to ChP capillaries and vessels in some regions. SARS-CoV-2 infection of brain tissue was confirmed by RT-qPCR in fragments of the ChP, lateral ventricle, and cortex. Interpretation Our results show multisystemic histopathological alterations caused by SARS-CoV-2 infection and contribute to knowledge regarding the course of fatal COVID-19 in children. Furthermore, our findings of ChP infection and viral neurotropism suggest that SARS-CoV-2 may invade the central nervous system by blood-cerebrospinal fluid barrier disruption. Funding Carlos Chagas Filho Foundation for Supporting Research in the State of Rio de Janeiro (FAPERJ); the National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES), in addition to intramural grants from D'Or Institute for Research and Education. Editor's Note This translation in Portuguese was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. Resumo Complicacoes sistemicas e neurologicas foram descritas em adultos com COVID-19 grave. Neste trabalho, descrevemos a infeccao por SARS-CoV-2, incluindo sua neuroinvasao, nos tecidos post-mortem de uma crianca. Metodos Realizamos a autopsia completa de uma crianca de 14 meses que morreu de pneumonite por COVID-19. Cortes histologicos de multiplos orgaos foram corados com Hematoxilina e Eosina. A coloracao de Luxol Fast Blue para mielina e imuno-histoquimica foram realizadas em areas selecionadas do cerebro. A presenca de SARS-CoV-2 foi investigada por imunomarcacao com anticorpo anti-proteina spike e por RT-qPCR. Achados As lesoes incluiram microtrombose, congestao pulmonar, edema intersticial, infiltrados linfociticos, lesao bronquiolar, colapso dos espacos alveolares, atrofia cortical e perda neuronal grave. A presenca de SARS-CoV-2 foi observada ao longo da regiao apical do epitelio do plexo coroide (PC) e nas celulas ependimarias do ventriculo lateral, mas ficou restrita aos capilares e vasos do PC em outras regioes. A infeccao do tecido cerebral por SARS-CoV-2 foi confirmada por RT-qPCR em fragmentos do PC, ventriculo lateral e cortex cerebral. Interpretacao Nossos resultados mostram alteracoes histopatologicas multissistemicas causadas pela infeccao por SARS-CoV-2 e contribuem para ampliar o conhecimento sobre a evolucao da COVID-19 fatal em criancas. Alem disso, nossos achados sobre a infeccao no PC e neurotropismo viral sugerem que o SARS-CoV-2 pode invadir o sistema nervoso central pela ruptura da barreira sangue-liquido cefalorraquidiano. Financiamento Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) e Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), alem de financiamento intramural do Instituto D'Or de Pesquisa e Educacao.