Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells

RationaleYoung 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. ObjectiveTo contrast the infection dynamics of SARS-CoV-2 in primary nasal epithelial cells from adults and children. MethodsViral 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 ResultsWe 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. ConclusionsOur 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. At a Glance CommentaryO_ST_ABSScientific Knowledge on the SubjectC_ST_ABSThere is now a growing body of evidence that children are less susceptible to SARS-CoV-2 infection compared to adults and if infected, children are more likely to develop an asymptomatic infection. The reasons for this remain unclear. In particular, the role of the pediatric nasal epithelium, the primary point of viral entry into the human host, in this differential susceptibility has yet to be investigated. What This Study Adds to the FieldOur study indicates that pediatric nasal epithelial cells produce a more vigorous anti-viral and pro-inflammatory response to SARS-CoV-2 compared to adult cells. This is associated with reduced SARS-CoV-2, but not influenza virus, replication in pediatric epithelial cells. We also show that on a protein level SARS-CoV-2 receptor expression on nasal epithelial cells is not significantly different between children and adults. These data provide an important insight into pediatric infections with SARS-CoV-2.