Background Noroviruses are an important viral cause of chronic diarrhea in immunocompromised individuals. Methods We collected norovirus-positive stool samples (n = 448) from immunocompromised patients (n = 88) at the National Institutes of Health (NIH) Clinical Research Center from 2010 to 2022. We assessed norovirus molecular epidemiology and infectivity in human intestinal enteroid (HIE) monolayers and clinical characteristics of the cohort. Results Noroviruses were genetically diverse: both genogroup I (GI.2, GI.5 and GI.6) and genogroup II (GII.1-GII.4, GII.6, GII.7, GII.12, GII.14, and GII.17) genotypes were detected, with GII.4 variants (Osaka, Apeldoorn, Den Haag, New Orleans, and Sydney) predominant (51/88 [57.9%]). Viruses belonging to the GII.4 Sydney variant group that replicated in HIEs (n = 9) showed a higher fold-increase in RNA genome copies compared to others that replicated. Chronic norovirus infection was documented in thirty-nine patients with shedding levels ranging from 104 to 1011 genome copies/g of stool. The majority (32/39 [82%]) had clinical evidence of an inborn error of immunity (13 identified monogenic diseases), most with combined immunodeficiency (15 of 32) or common variable immunodeficiency (11 of 32). Conclusions Genetically and biologically diverse noroviruses established chronic infection in NIH patients with both inborn and acquired immunologic defects.

中文翻译：

---

美国国立卫生研究院临床研究中心十年慢性诺如病毒感染监测：临床特征、分子流行病学和复制


背景 诺如病毒是免疫功能低下个体慢性腹泻的重要病毒原因。方法 我们收集了 2010 年至 2022 年在美国国立卫生研究院 （NIH） 临床研究中心免疫功能低下患者 （n = 448） 的诺如病毒阳性粪便样本 （n = 88）。我们评估了人肠道样肠杆菌 （HIE） 单层中的诺如病毒分子流行病学和感染性以及队列的临床特征。结果 诺如病毒基因多样：基因群 I （GI.2、GI.5 和 GI.6） 和基因群 II （GII.1-GII.4、GII.6、GII.7、GII.12、GII.14 和 GII.17） 基因型均存在，其中 GII.4 变异 （大阪、阿珀尔多伦、海牙、新奥尔良和悉尼） 占主导地位 （51/88 [57.9%]）。属于 GII.4 Sydney 变体组的病毒在 HIEs 中复制 （n = 9） 显示出与其他复制的病毒相比，RNA 基因组拷贝数的倍数增加更高。39 例患者记录了慢性诺如病毒感染，脱落水平从 104 到 1011 个基因组拷贝/g 粪便不等。大多数 （32/39 [82%]）有先天性免疫缺陷的临床证据 （13 种已确定的单基因疾病），大多数患有联合免疫缺陷 （32 例中的 15 例） 或普通变异型免疫缺陷 （32 例中的 11 例）。结论 遗传学和生物学多样性的诺如病毒在先天性和获得性免疫缺陷的 NIH 患者中确立了慢性感染。