One of the biggest mysteries of the new coronavirus is its relative harmlessness in most children who get infected.
At least part of the explanation may be in the cells lining their noses, according to a new study by researchers at the Icahn School of Medicine at Mount Sinai in New York City.
The researchers started with archived samples of cells from the nasal lining, or epithelium, of people ages 4 to 60. Then they measured the activity of a gene that directs production of ACE2, a protein that helps coronavirus enter the body. It turned out that ACE2 gene "expression" -- the DNA instructions that are converted into a functional molecule -- was lower in young children, and that expression increased with age.
"Few studies have examined the relationship between ACE2 in the airway and age," the team wrote in a letter published in JAMA Network. "The results from this study show age-dependent expression of ACE2 in nasal epithelium, the first point of contact for (the coronavirus) and the human body. "
The implications of that are intriguing, but not yet clear, said Ishminder Kaur, an epidemiologist and infectious-disease specialist at St. Christopher's Hospital for Children in Philadelphia. The reduced ACE2 gene expression in children suggests, but doesn't prove, that children create less of the protein that the virus uses as its gateway, or receptor.
"It's a signal, but does that translate to lower protein production, or less receptor activity?" Kaur asked. "Like any good study, it generates its own set of questions."
ACE2 (short for angiotensin converting enzyme 2) is part of a complex system that regulates blood pressure, fluid, and mineral balance in the body. Because ACE2 also helps the coronavirus take hold in the nose, lungs, and other organs, it has become a subject of interest. For example, researchers are studying whether common blood pressure medicines that stimulate ACE2 can make COVID-19 more deadly -- or less so because ACE2 tamps down inflammation and tissue scarring.
The mystery of COVID-19 in children has been as puzzling as it is a relief. Children, who make up fewer than 2% of identified cases, generally have mild symptoms or none, and rarely die of the infection.
That's the opposite of the seasonal influenza, which can be devastating in young children because their immune systems have not matured, and they don't have prior exposure to most flu strains. Flu vaccination is recommended to protect them.
But immune response may be just part of the puzzle.