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

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.

Understanding why superspreading drives the COVID-19 pandemic but not the H1N1 pandemic

“…11 The mechanistic basis of these determinants of overdispersion is a promising area of study. For example, intrinsic case heterogeneity in shedding could arise from individual differences in susceptibility, previous exposures, immunity, or viral host factors, 10,[12][13][14] or could be related to phenomena associated with recent zoonotic spillover. In the event that common molecular mechanisms are indicated with k, 14 they could guide the rational design of hostdirected therapies that reduce the incidence of superspreading for those virus classes.…”

“… 5 Children and adolescents contribute more to the transmission of common cold betacoronaviruses and influenza than they do to the emerging betacoronaviruses. However, despite the association of young age with high contact patterns and susceptibility to influenza and common cold betacoronaviruses, 9 , 10 these viruses are infrequently involved in superspreading events.…”

Human models for COVID‐19 research

“…All of which have demonstrated distinct phenotypic and/or functional characteristics in ALIculture (Clunes et al, 2012;Bilodeau et al, 2016;Castellani et al, 2018;Carlier et al, 2018;Gaiha et al, 2020;Woodall et al, 2020;Zhu et al, 2021).…”

“…Although, the role of entry factors in determining disease severity remains inconclusive. Other studies suggest that the immune response to SARS-CoV-2 may play a more important role (Koch et al, 2021), with elevated production of type I and III interferons, rather than differential receptor expression, suggested as the cause of the lower viral replication in paediatric compared to adult nasal epithelial cultures (Zhu et al, 2021).…”

“…2021), with elevated production of type I and III interferons, rather than differential receptor expression, suggested as the cause of the lower viral replication in paediatric compared to adult nasal epithelial cultures (Zhu et al . 2021).…”