Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells

PLoS Biol. 2022 Aug 1;20(8):e3001728. doi: 10.1371/journal.pbio.3001728. eCollection 2022 Aug.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • COVID-19*
  • Child
  • Epithelial Cells
  • Humans
  • SARS-CoV-2* / genetics

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This work is supported by the Australia Research Council (Discovery Early Career Researcher Award DE190100565 to M.J.), The National Health and Medical Research Council (Project grant APP2010917 to F.A.M. and G.B.; Senior research Fellowship APP1155794 to F.A.M; APP1124612 to LL; 2010757 to KYC and LL; NHMRC investigator grant 2007919 to K.R.S.) the Australian Infectious Diseases Research Centre (COVID-19 seed grant to A.A.K) and Academy of Finland and COVID19 research donations (Grant 318434 to G.B.). This program has in part been funded by the Western Australian Future Health Research & Innovation Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.