Yanshan Zhu, Keng Yih Chew, Anjana C. Karawita, Ayaho Yamamoto, Larisa L. Labzin, Tejasri Yarlagadda, Alexander A. Khromykh, Claudia J. Stocks, Yao Xia, Tobias R. Kollmann, David Martino, Anthony Kicic, Helle Bielefeldt-Ohmann, Asha C. Bowen, Peter D. Sly, Kirsten M. Spann, Kirsty R. Short
Abstract
Rationale: Young children (typically those <10 years old) are less susceptible to SARS-CoV-2 infection and symptoms compared to adults. However, the mechanisms that underlie these age-dependent differences remain to be determined and could inform future therapeutics for adults. Objective: To contrast the infection dynamics of SARS-CoV-2 in primary nasal epithelial cells from adults and children. Methods: Viral replication was quantified by plaque assay. The cellular transcriptome of infected and uninfected cells was assessed by RNA-seq. ACE2 and TMPRSS2 protein expression were quantified by Western Blot Measurements and Main Results: We report significantly higher SARS-CoV-2 replication in adult compared to pediatric nasal epithelial cells. This was restricted to SARS-CoV-2 infection, as the same phenomenon was not observed with influenza virus infection. The differentiational SARS-CoV-2 replication dynamics were associated with an elevated type I and III interferon response, and a more pronounced inflammatory response in pediatric cells. No significant difference between the two age groups was observed in the protein levels of ACE2 and TMPRSS2. Conclusions: Our data suggest that the innate immune response of pediatric nasal epithelial cells, and not differential receptor expression, may contribute to the reported reduced SARS-COV-2 infection and symptoms reported amongst children.
Competing Interest Statement
The authors have declared no competing interest.
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