Nasal Cells in Children Shield Against Severe COVID-19

Children usually have milder COVID-19 symptoms; this could be due to differences in how elderly and young people's nasal cells react to the SARS-CoV-2 virus.

The study's funding sources include the Chan Zuckerberg Foundation, Wellcome, Great Ormond Street Hospital Biomedical Research Center, National Institute for Health and Care Research, and UK Research and Innovation.

The early effects of SARS-CoV-2 infection on human nasal epithelial cells (NECs), the cells that the viruses initially targeted, were the main focus of the study.

Participants in good health from University College London Hospital, Great Ormond Street Hospital, and the Royal Free Hospital donated the cells.

Among the participants were adults between the ages of 30 and 50, adults over the age of 70, and children under the age of 11.

Specialized Techniques

The cells were cultured using specialized methods, which allowed them to proliferate back into the various cell types that were initially found in the nose.

The group identified 24 different types of epithelial cells using single-cell RNA sequencing techniques, which allow scientists to determine the distinct genetic networks and functions of thousands of individual cells.

After that, cultures from every age group were either SARS-CoV-2-infected or mock-infected.

Anti-viral Effect

After three days, the study discovered that children's NECs quickly reacted to SARS-CoV-2 by increasing interferon, the body's first line of defense against viruses, and limiting viral replication. The study was published in Nature Microbiology.

But as people aged, this early antiviral effect diminished.

The researchers discovered that NECs from elderly people had higher levels of cell shedding and damage in addition to producing more infectious virus particles.

Younger people usually have milder symptoms, which could be explained by the strong antiviral response in their NECs.

On the other hand, the severity of the disease seen in older adults may be related to the increased damage and higher viral replication found in NECs from elderly individuals.

More Detailed Understanding

Our research reveals how the type of cells we have in our nose changes with age, and how this affects our ability to combat SARS-CoV-2 infection. This could be crucial in developing effective anti-viral treatments tailored to different age groups, especially for the elderly who are at higher risk of severe COVID-19.”

Dr. Claire Smith, Project Lead, UCL Great Ormond Street Institute of Child Health

Dr. Kerstin Meyer, Co-Senior Author, Wellcome Sanger Institute, said, “By carrying out SARS-CoV-2 infections of epithelial cells in vitro and studying the responses with single cell sequencing, we get a much more detailed understanding of the viral infection kinetics and see big differences in the innate immune response between cell types.”

The Importance of Considering Age as a Critical Factor

While respiratory failure is rare in children infected with SARS-CoV-2, mortality remains a significant risk for infected adults over 85 years of age, even with improved treatment options and vaccination.

The findings highlight the significance of taking age into account when studying and treating infectious diseases.

“It is fascinating that when we take away immune cells from nasal samples and are only left with nasal epithelial cells grown in a dish, we are still able to identify age-specific differences in our body’s response to the SARS-CoV-2 between the young and elderly to explain why children are generally protected from severe COVID-19,” noted Co-senior author, Dr Marko Nikolic, from the UCL Division of Medicine.

Long-Term Implications

Understanding the cellular differences at the initiation of infection is just the beginning. We now hope to investigate the long-term implications of these cellular changes and test therapeutic interventions using our unique cell culture model. This ‘gold-standard’ system is only possible with the support of our funders and the willingness of participants to provide their samples.”

Dr. Claire Smith, Project Lead, UCL Great Ormond Street Institute of Child Health

The team proposes that future research should investigate how aging affects the body's response to various viral infections.