Nasal cells protect children against severe COVID-19

A recent study led by researchers at the University College London (UCL) and the Wellcome Sanger Institute has unveiled significant differences in the way nasal cells from young and elderly individuals respond to the SARS-CoV-2 virus. This discovery provides new insights into why children generally exhibit milder COVID-19 symptoms compared to older adults. 

The findings shed light on the initial interactions between the virus and human nasal epithelial cells (NECs), which are among the first cells targeted by the virus.

Focus of the study

“Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high,” wrote the study authors.

“Here we investigate differences in the cellular landscape and function of pediatric (<12 years), adult (30–50 years) and older adult (>70 years) ex vivo cultured nasal epithelial cells in response to infection with SARS-CoV-2.”

Analysis of nasal cells exposed to the virus

The researchers analyzed nasal cells donated by healthy individuals across all three age groups to the Great Ormond Street Hospital (GOSH), University College London Hospital (UCLH), and the Royal Free Hospital.

The cells were cultured to regrow into the diverse cell types originally found in the nasal passages. Employing advanced single-cell RNA sequencing techniques, the researchers identified 24 distinct types of epithelial cells. Each age group’s cultures were then exposed to SARS-CoV-2 in controlled experiments.

Children’s nasal cells mounted a rapid response 

Three days post-infection, the results showed that children’s nasal cells mounted a rapid response by increasing the production of interferon, a critical component of the body’s initial antiviral defense, which effectively restricted viral replication. However, this robust antiviral response was found to diminish with age.

In elderly individuals, the NECs not only produced more infectious virus particles but also exhibited increased cellular shedding and damage. This could explain the higher severity of COVID-19 symptoms and complications seen in older adults.

Age-related changes in nasal cells 

“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 antiviral treatments tailored to different age groups, especially for the elderly who are at higher risk of severe COVID-19,” explained project leader Claire Smith, an associate professor in infection, immunity, and inflammation at UCL Great Ormond Street Institute of Child Health.

“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,” added co-senior author Kerstin Meyer, an expert in cellular genetics at the Wellcome Sanger Institute.

Age is the single greatest risk factor

Despite the advancements in vaccination and treatment options, the mortality risk remains high for those over 85 who contract the virus. This research emphasizes the importance of age as a critical factor in both the study and treatment of infectious diseases.

“Despite effective vaccines, age remains the single greatest risk factor for COVID-19 mortality. Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rarely develop severe disease, while the mortality in infected people over 85 years is currently as high as 1 in 10,” noted the researchers.

Age-specific differences in our body’s response

“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,” said co-senior author Marko Nikolic, a clinical scientist the UCL Division of Medicine.

“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,” Smith concluded.

The researchers suggest that future studies should explore how aging affects the body’s response to other viral infections, potentially leading to more age-specific medical strategies.

The study is published in the journal Nature Microbiology.

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