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Cultivate Primary Nasal Epithelial Cells from Children and Reprogram into Induced Pluripotent Stem Cells
Published on: March 10, 2016
Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells
Yanshan Zhu1, Keng Yih Chew1, Melanie Wu1
1School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
Insights
Children
Area of Science:
- Virology
- Pediatric Infectious Diseases
- Immunology
Background:
- Children generally exhibit milder Coronavirus Disease 2019 (COVID-19) symptoms and lower susceptibility to SARS-CoV-2 infection compared to adults.
- Emergence of SARS-CoV-2 variants of concern (VOCs) correlates with increased pediatric infections, prompting investigation into underlying causes.
Purpose of the Study:
- To investigate differences in SARS-CoV-2 replication and antiviral responses in pediatric versus adult nasal epithelial cells (NECs).
- To compare the susceptibility of pediatric NECs to ancestral SARS-CoV-2 and its VOCs, including Delta and Omicron variants.
Main Methods:
- Primary nasal epithelial cells (NECs) from children and adults were differentiated at an air-liquid interface.
- These NECs were infected with ancestral SARS-CoV-2, Delta, and Omicron variants to assess viral replication and host antiviral responses.
Main Results:
- Ancestral SARS-CoV-2 replicated to significantly lower titers in pediatric NECs compared to adult NECs, associated with a heightened antiviral response.
- The Delta variant also showed reduced replication in pediatric NECs, whereas Omicron replicated more efficiently in pediatric NECs than Delta or the ancestral strain.
- Omicron variant demonstrated higher viral RNA levels in pediatric NECs compared to Delta and ancestral SARS-CoV-2.
Conclusions:
- Pediatric nasal epithelium inherently supports lower replication of ancestral SARS-CoV-2, linked to a robust antiviral defense.
- The evolving SARS-CoV-2 landscape, particularly with variants like Omicron, may alter this differential susceptibility in children's nasal passages.
Abstract:
Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.
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