原发性免疫缺陷和免疫功能正常儿科患者鼻咽及粪便样本中新冠病毒的排泄及基因进化
SARS-CoV-2 excretion and genetic evolution in nasopharyngeal and stool samples from primary immunodeficiency and immunocompetent pediatric patients.
作者信息
Khemiri Haifa, Ben Fraj Ilhem, Lorusso Alessio, Mekki Najla, Mangone Iolanda, Gdoura Mariem, Di Pasqual Adriano, Cammà Cesare, Di Lollo Valeria, Cherni Asma, Touzi Henda, Sadraoui Amel, Meddeb Zina, Hogga Nahed, Ben Mustapha Imen, Barbouche Mohamed-Ridha, Ouederni Monia, Triki Henda, Haddad-Boubaker Sondes
机构信息
Laboratory of Clinical Virology, WHO Regional Reference Laboratory for Poliomyelitis and Measles for in the Eastern Mediterranean Region, Institut Pasteur de Tunis, University of Tunis El Manar, 13 place Pasteur, BP74 1002 le Belvédère, Tunis, Tunisia.
Research Laboratory "Viruses, Vectors and Hosts" (LR20IPT02), Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia.
出版信息
Virol J. 2025 Jan 13;22(1):9. doi: 10.1186/s12985-025-02628-7.
BACKGROUND
Primary Immunodeficiency disorders (PID) can increase the risk of severe COVID-19 and prolonged infection. This study investigates the duration of SARS-CoV-2 excretion and the genetic evolution of the virus in pediatric PID patients as compared to immunocompetent (IC) patients.
MATERIALS AND METHODS
A total of 40 nasopharyngeal and 24 stool samples were obtained from five PID and ten IC children. RNA detection was performed using RT-qPCR, and whole-genome sequencing was conducted with the NexSeq 1000 platform. Data analysis used the nextflow/viralrecon pipeline. Hotspot amino acid frequencies were investigated using GraphPad Prism v10. Phylodynamic analysis was conducted with BEAST software.
RESULTS
In IC children, the viral excretion period lasted up to 14 days in nasopharyngeal swabs, with an average duration of 7 days, and ranged from 7 to 14 days in stool samples. In PID patients, the viral RNA was detected in nasopharyngeal for periods between 7 and 28 days, with an average duration of 15 days, and up to 28 days in stool samples. Two SARS-CoV-2 variants were detected in PID patients: Delta (AY.122) and Omicron (BA.1.1). Patients with antibody and combined deficiencies, exhibited the most prolonged shedding periods in both nasopharyngeal and stool samples and one patient presented complications and fatal outcome. Specific Hotspot amino acid changes were detected in PID: A2821V and R550H (ORF1ab).
CONCLUSION
Our findings underscore the prolonged excretion of SARS-CoV-2 RNA in patients with antibody and combined deficiencies. Thus, specialized care is essential for effectively managing PID patients.
背景
原发性免疫缺陷病（PID）会增加患重症 COVID-19 和长期感染的风险。本研究调查了与免疫功能正常（IC）的患者相比，儿童 PID 患者中 SARS-CoV-2 排泄持续时间及病毒的基因进化情况。
材料与方法
从 5 名 PID 儿童和 10 名 IC 儿童中总共获取了 40 份鼻咽样本和 24 份粪便样本。使用 RT-qPCR 进行 RNA 检测，并使用 NexSeq 1000 平台进行全基因组测序。数据分析采用 nextflow/viralrecon 流程。使用 GraphPad Prism v10 研究热点氨基酸频率。用 BEAST 软件进行系统发育动力学分析。
结果
在 IC 儿童中，鼻咽拭子中病毒排泄期最长可达 14 天，平均持续时间为 7 天，粪便样本中为 7 至 14 天。在 PID 患者中，鼻咽中病毒 RNA 检测到的时间为 7 至 28 天，平均持续时间为 15 天，粪便样本中最长可达 28 天。在 PID 患者中检测到两种 SARS-CoV-2 变体：Delta（AY.122）和 Omicron（BA.1.1）。抗体和联合免疫缺陷患者在鼻咽和粪便样本中的病毒脱落期最长，1 例患者出现并发症并死亡。在 PID 患者中检测到特定的热点氨基酸变化：A2821V 和 R550H（ORF1ab）。
结论
我们的研究结果强调了抗体和联合免疫缺陷患者中 SARS-CoV-2 RNA 的排泄时间延长。因此，对 PID 患者进行有效管理，专业护理至关重要。
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