Covid-19: Another reason why children avoid severe symptoms

  • Recently published research reveals yet another reason why Covid-19 seems to spare young children
  • In the study, researchers found that children have lower levels of an enzyme that the virus needs to invade cells in the lung
  • Drugs that block the enzyme are currently being tested for Covid-19 treatment

Experts have found that children are mostly spared from the effects of Covid-19 – caused by SARS-CoV-2 – and if infected, often present with only mild symptoms.

Some studies have suggested that children's lung physiology and immune function could serve as protection, while others have suggested that their blood vessels are better able to withstand a viral attack.

In a newly published study, a team of researchers from Vanderbilt University Medical Center (VUMC) in Nashville, Tennessee and their colleagues found another key reason why Covid-19 spares younger children.

According to their findings, published in the Journal of Clinical Investigation, children have lower levels of an enzyme (or co-receptor) that SARS-CoV-2 needs to invade airway epithelial cells in the lungs.

"Our study provides a biologic rationale for why particularly infants and very young children seem to be less likely to either get infected or to have severe disease symptoms," Jennifer Sucre, MD, assistant professor of Pediatrics (Neonatology), who led the research with Jonathan Kropski, MD, assistant professor of Medicine, said in a news release published in May, when the study was posted online by the preprint server bioRxiv.

The results also support existing efforts to block the enzyme to potentially treat or prevent Covid-19 in older people, the authors noted.

TMPRSS2's role in shielding children

The enzyme, type II transmembrane serine protease (TMPRSS2), plays a critical role in SARS-CoV-2 infection, in that it enables the virus to fuse into the cell membrane and “break into” the cell, ultimately hijacking the cell’s genetic material to make copies of its RNA.

Sucre and Kropski considered whether TMPRSS2 plays a role in severe Covid-19 cases observed in older people compared to children.

"Our research has always focused on understanding lung development and how infant lungs differ from adult lungs in their vulnerability to injury," Sucre said. "In this study, we actually took the opposite approach, and were able to see how the developing lung by its differences is protected from SARS-CoV-2 infection."

Using a technique called single-cell RNA-sequencing, the research team then built a dataset on lung development in mice, which can detect the expression of genes in individual cells of tissues, such as the lung.

Through this method, they were able to track the expression of genes known to be involved in the body's response to Covid-19 over time.

More TMPRSS2 found in older adults

They found that while the gene for angiotensin-converting enzyme 2s, called ACE2 (the receptors that allow the virus to enter the body’s cells) was expressed at low levels in the lungs of mice. "TMPRSS2 stood out as having a really striking trajectory of increased expression during development," Schuler said.

Together with VUMC pathologists, the researchers obtained and analysed human lung specimens collected from donors of different ages, and confirmed a similar trajectory in TMPRSS2 expression to what they'd found in mice.

"What we found is that expression of (TMPRSS2) goes up significantly with ageing, and we see that at the level of the gene and at the level of the protein," Sucre said.

"We see a lot more TMPRSS2 in older individuals, in both humans and mice."

Enzyme also linked to prostate cancer

The researchers wrote that TMPRSS2 is also well known for its role in the development of prostate cancer.

Drugs that block the enzyme, and which have already been approved for the treatment of advanced prostate cancer, are currently being tested clinically as potential treatments for Covid-19 as well.

"We do think TMPRSS2 could be an attractive target both in treatment and potentially as a prophylaxis (preventing infection) for people at high risk of Covid exposure," Sucre said.

READ | Children are more resilient against Covid-19, study shows

READ | A common Covid-19 virus mutation may make it more susceptible to vaccines

READ | More scientific reasons why children are largely sheltered from Covid-19

Image: Getty/Volanthevist

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