An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C.
An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C.
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DOI：
10.1016/j.eclinm.2021.100850
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发表时间：
2021-05
影响因子：
15.1
通讯作者：
Dolhnikoff M
中科院分区：
文献类型：
--
作者：
Duarte-Neto AN;Caldini EG;Gomes-Gouvêa MS;Kanamura CT;de Almeida Monteiro RA;Ferranti JF;Ventura AMC;Regalio FA;Fiorenzano DM;Gibelli MABC;Carvalho WB;Leal GN;Pinho JRR;Delgado AF;Carneiro-Sampaio M;Mauad T;Ferraz da Silva LF;Saldiva PHN;Dolhnikoff M
儿童中的COVID-19通常是轻微或无症状的，但也有严重和致命的儿科病例。COVID-19在儿童中的病理尚不清楚；严重病例的发病机制包括免疫介导机制或SARS-CoV-2对组织的直接作用。我们描述了5例小儿COVID-19的尸检结果，并提供了有关该疾病发病机制的机制见解。对2020年3月18日至8月15日期间因新冠肺炎死亡的儿童和青少年进行了微创尸检。采用组织学、电子显微镜（EM）、逆转录聚合酶链反应（RT-PCR）和免疫组织化学（IHC）对所有重要器官的组织样本进行分析。5例患者，男1例，女4例，年龄7个月至15岁。2例患者在感染SARS-CoV-2前有严重疾病：肾上腺癌和爱德华兹综合征。3例患者既往健康，患有儿童多系统炎症综合征（MIS-C），具有不同的临床表现：心肌炎、结肠炎和急性脑病伴癫痫持续状态。患者的尸检结果各不相同，包括轻度至重度COVID-19肺炎、肺微血栓形成、脑水肿伴反应性胶质增生、心肌炎、肠道炎症和噬血细胞症。通过至少一种方法（RT-PCR、免疫组化或EM）在所有患者的肺、心脏和肾脏中检测到SARS-CoV-2，并在2例MIS-C（免疫组化）患者的心脏和大脑内皮细胞中检测到SARS-CoV-2。此外，我们首次发现SARS-CoV-2存在于患有急性脑病的misc儿童的脑组织和患有急性结肠炎的儿童的肠道组织中。解释：SARS-CoV-2可感染儿科患者的多种细胞和组织类型，临床表现的靶器官因人而异。观察到两种主要的COVID-19模式：主要是肺部疾病，伴有严重急性呼吸系统疾病和弥漫性肺泡损伤，或多系统炎症综合征，累及多个器官。SARS-CoV-2在多个器官中的存在，并与细胞超微结构变化相关，强化了SARS-CoV-2对组织的直接影响参与MIS-C发病机制的假设。圣保罗州教育基金会、巴西国家环境保护协会Científico e Tecnológico、比尔及梅林达·盖茨基金会。
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. 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). 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. Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Bill and Melinda Gates Foundation.
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DOI：
10.1016/s1474-4422(20)30308-2
发表时间：
2020-11
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Matschke J;Lütgehetmann M;Hagel C;Sperhake JP;Schröder AS;Edler C;Mushumba H;Fitzek A;Allweiss L;Dandri M;Dottermusch M;Heinemann A;Pfefferle S;Schwabenland M;Sumner Magruder D;Bonn S;Prinz M;Gerloff C;Püschel K;Krasemann S;Aepfelbacher M;Glatzel M
通讯作者：
Glatzel M
影响因子：
6.9
作者：
Chan, K-H;Sridhar, S.;Yuen, K-Y
通讯作者：
Yuen, K-Y
影响因子：
36.4
作者：
Goetzinger, Florian;Santiago-Garcia, Begona;Tebruegge, Marc
通讯作者：
Tebruegge, Marc
影响因子：
7.3
作者：
Hamming, I;Timens, W;van Goor, H
通讯作者：
van Goor, H
影响因子：
8.1
作者：
Grimaud, Marion;Starck, Julie;Oualha, Mehdi
通讯作者：
Oualha, Mehdi