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SARS-CoV-2 excretion and genetic evolution in nasopharyngeal and stool samples from primary immunodeficiency and
Haifa Khemiri1,2, Ilhem Ben Fraj3, Alessio Lorusso4
1Laboratory 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. haifa.khemiri@pasteur.utm.tn.
Insights
Primary Immunodeficiency disorders (PID) lead to prolonged SARS-CoV-2 excretion in children. Antibody and combined deficiencies showed the longest viral shedding, highlighting the need for specialized care in these patients.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Primary Immunodeficiency disorders (PID) increase the risk of severe COVID-19 and prolonged SARS-CoV-2 infection.
- This study compares viral excretion duration and genetic evolution in pediatric PID patients versus immunocompetent (IC) children.
Purpose of the Study:
- To investigate the duration of SARS-CoV-2 excretion in pediatric PID patients.
- To analyze the genetic evolution of SARS-CoV-2 in pediatric PID patients.
- To compare viral shedding and evolution between PID and IC pediatric patients.
Main Methods:
- Collected nasopharyngeal and stool samples from five PID and ten IC children.
- Utilized RT-qPCR for RNA detection and whole-genome sequencing (NexSeq 1000).
- Analyzed data using nextflow/viralrecon, GraphPad Prism v10, and BEAST software for phylodynamic analysis.
Main Results:
- Viral RNA detected up to 14 days in IC children (nasopharyngeal) and up to 28 days in PID patients.
- PID patients exhibited prolonged shedding (average 15 days nasopharyngeal, up to 28 days stool).
- Delta (AY.122) and Omicron (BA.1.1) variants found in PID patients; specific amino acid changes (A2821V, R550H) noted.
Conclusions:
- Prolonged SARS-CoV-2 RNA excretion observed in PID patients, particularly those with antibody and combined deficiencies.
- One PID patient experienced complications and a fatal outcome.
- Specialized care is crucial for managing PID patients with COVID-19.
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.
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