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Case report: hepatitis in a child infected with SARS-CoV-2 presenting toll-like receptor 7 Gln11Leu single nucleotide polymorphism
Virology Journal ( IF 4.8 ) Pub Date : 2021-09-05 , DOI: 10.1186/s12985-021-01656-3
Natália Lima Pessoa 1, 2 , Aline Almeida Bentes 3, 4 , Andrea Lucchesi de Carvalho 4 , Thaís Bárbara de Souza Silva 2 , Pedro Augusto Alves 2 , Erik Vinicius de Sousa Reis 2 , Tayse Andrade Rodrigues 1, 5 , Erna Geessien Kroon 1 , Marco Antônio Campos 2
Affiliation  

Covid-19 has the respiratory tract as the main target of infection, and patients present mainly dyspnea, pneumonia, dry cough, and fever. Nevertheless, organs outside the respiratory tract had been reported in recent studies, including the gastrointestinal tract and liver. The host innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through their pattern recognition receptor (PRRs). Toll-like receptor 7 (TLR-7) is a pattern recognition receptor recognizing ssRNA (SARS-CoV-2 is an ssRNA). Polymorphisms are characterized by two or more alternative forms of a distinct phenotype in the same population. Polymorphisms in tlrs genes can negatively influence the immune response to infectious diseases. There are several references in the literature to non-synonymous single nucleotide (rs) polymorphisms related to several genes. Some of them are important for the innate immunity, as rs 179008 (tlr-7), rs3775291 (tlr3), rs8177374 (tir domain-containing adaptor protein, tirap), rs1024611 (monocyte chemoattractant protein-1, mcp-1) and rs61942233 (2′-5′-oligoadenylate synthase-3, oas-3). We identified a 5-year-old-male child with gastrointestinal symptoms and fever presenting acholic stool and jaundice, who was positive for SARS-CoV-2 IgM, IgA, and IgG and presenting the Gln11Leu rs 179008 in tlr-7. The child presented high levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, C-reactive protein, D-dimer, gamma-glutamyl transferase, alkaline phosphatase, and was negative for serological tests for hepatitis A, B, C, E, HIV 1 and 2, herpes virus, cytomegalovirus, Epstein–Barr virus, and negative for RTqPCR for Influenza A and B, RSV and SARS-CoV-2. We also investigated other SNPs in the tlr-3 (rs3775291), tirap (rs8177374), mcp-1 (rs1024611), and oas-3 (rs61942233) genes, and no mutation was detected. After an interview with the child's caregivers, any possible accidental ingestion of drugs or hepatotoxic substances was ruled out. To our knowledge, this is the first report of a SARS-CoV-2 caused hepatitis in a male child that has the tlr-7 Gln11Leu rs 179008, which could impair an efficient initial immune response. The knowledge of the patient's immune deficiency could improve the treatment to correct this deficiency with specific medications.

中文翻译:

病例报告:感染 SARS-CoV-2 的儿童肝炎呈现 toll 样受体 7 Gln11Leu 单核苷酸多态性

Covid-19以呼吸道为主要感染对象,患者主要表现为呼吸困难、肺炎、干咳、发热等。然而,最近的研究报告了呼吸道以外的器官,包括胃肠道和肝脏。宿主先天免疫系统通过其模式识别受体 (PRR) 识别病原体相关分子模式 (PAMP)。Toll 样受体 7 (TLR-7) 是一种模式识别受体,可识别 ssRNA(SARS-CoV-2 是一种 ssRNA)。多态性的特征在于同一群体中不同表型的两种或多种替代形式。tlrs 基因的多态性会对传染病的免疫反应产生负面影响。文献中有几个关于与几个基因相关的非同义单核苷酸 (rs) 多态性的参考文献。其中一些对先天免疫很重要,如 rs 179008 (tlr-7)、rs3775291 (tlr3)、rs8177374(含 tir 结构域的衔接蛋白,tirap)、rs1024611(单核细胞趋化蛋白-1,mcp-1)和 rs61942233 (2'-5'-寡腺苷酸合酶 3,oas-3)。我们确定了一名 5 岁男孩,有胃肠道症状和发烧,表现为无胆便和黄疸,其 SARS-CoV-2 IgM、IgA 和 IgG 呈阳性,并在 tlr-7 中呈现 Gln11Leu rs 179008。该儿童出现高水平的天冬氨酸氨基转移酶、丙氨酸氨基转移酶、胆红素、C-反应蛋白、D-二聚体、γ-谷氨酰转移酶、碱性磷酸酶,甲型、乙型、丙型、戊型、HIV 1 和2、疱疹病毒、巨细胞病毒、爱泼斯坦-巴尔病毒,对甲型和乙型流感、RSV 和 SARS-CoV-2 的 RTqPCR 呈阴性。我们还研究了 tlr-3 (rs3775291)、tirap (rs8177374)、mcp-1 (rs1024611) 和 oas-3 (rs61942233) 基因中的其他 SNP,未检测到突变。在与孩子的看护人面谈后,排除了任何可能的意外摄入药物或肝毒性物质。据我们所知,这是第一份关于 SARS-CoV-2 导致男孩患有 tlr-7 Gln11Leu rs 179008 肝炎的报告,这可能会损害有效的初始免疫反应。了解患者的免疫缺陷可以改善治疗,以使用特定药物纠正这种缺陷。排除了任何可能的意外摄入药物或肝毒性物质。据我们所知,这是第一份关于 SARS-CoV-2 导致男孩患有 tlr-7 Gln11Leu rs 179008 肝炎的报告,这可能会损害有效的初始免疫反应。了解患者的免疫缺陷可以改善治疗,以使用特定药物纠正这种缺陷。排除了任何可能的意外摄入药物或肝毒性物质。据我们所知,这是第一份关于 SARS-CoV-2 导致男孩患有 tlr-7 Gln11Leu rs 179008 肝炎的报告,这可能会损害有效的初始免疫反应。了解患者的免疫缺陷可以改善治疗,以使用特定药物纠正这种缺陷。
更新日期:2021-09-06
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