Supinda Bunyavanich, MD, MPH, and post-doctoral fellow Scott Tyler, PhD. File photo.
On Saturday, March, 14, as the U.S. economy was beginning to shut down due to the COVID-19 pandemic, Supinda Bunyavanich, MD, MPH, a mother of two young children and a Professor of Genetics and Genomic Sciences, and Pediatrics, at the Icahn School of Medicine at Mount Sinai, had a “eureka” moment.
“I was at home thinking about the world and how New York City was being hit, and I realized so much is unknown about this virus,” Dr. Bunyavanich recalls. As a parent, Dr. Bunyavanich says she was relieved to read that children appeared to be less susceptible to catching COVID-19 than the rest of the population based on reports from China, although no one knew precisely why.
Dr. Bunyavanich was on the phone that day with Alfin Vicencio, MD, Chief of Pediatric Pulmonology at the Icahn School of Medicine at Mount Sinai. They discussed how the SARS-CoV-2 virus, which causes COVID-19, might enter the body through ACE2 receptors—proteins on the surface of many cells, including those found in the lining of the nose. At that moment, she realized she had important data that connected both lines of research.
“I thought, ‘wait a minute,’ ” Dr. Bunyavanich says. “COVID-19 is a respiratory condition. I have data on what’s happening in the noses of people of many ages from my studies of asthma. Could it be that kids have fewer access points for the virus to enter?’”
In May, JAMA published the novel findings from Dr. Bunyavanich’s data, which showed that lower ACE2 expression in children relative to adults may help explain why the disease is less prevalent in young children.
“The degree to which we express ACE2 may play into how susceptible we are to the SARS-CoV-2 virus,” Dr. Bunyavanich says. “Our finding that there are age-related differences in the level of ACE2 is consistent with epidemiologic data from around the world that children suffer less from COVID-19. Lower nasal expression of ACE2 in children is a concrete finding from our study that might explain why children are less affected by SARS-CoV-2.”
Interestingly, Dr. Bunyavanich’s data are from a Mount Sinai study she has been leading for a few years that looks for nasal biomarkers for asthma. The data, part of a study of 305 individuals between the ages of 4 and 60, includes “an atlas of genes that a person expresses in their nose,” she says. “The original project wasn’t targeted to ACE2, but we had this library of information on hand, so we homed in on ACE2 given its potential role in COVID-19.”
The researchers found that young children have the least expression of ACE2 in their nasal passages and that the quantity increases with age, so that children 10 to 17 years of age have more than younger children, but less than young adults age 18 to 24. The highest level was found in individuals 25 and older.
It is possible, she says, that young children have plenty of virus particles in their noses, but perhaps they are less likely to enter the body. “Think of ACE2 as a doorknob that SARS-CoV-2 uses to get in. There might be plenty of virus waiting to get through the door, but it has a harder time compared to adults,” she says. “The virus won’t cause illness if it can’t get in.”
According to Diana W. Bianchi, MD, Director of the National Institute of Child Health and Human Development, young children tend to be mildly affected by COVID-19, and relatively few end up in intensive care units. Their symptoms also present differently than those in adults, with diarrhea, abdominal pain, and other gastrointestinal problems.
Many questions surrounding children and COVID-19 continue to be the focus of widespread debate, particularly as communities consider whether to reopen schools in the fall.
“In-person learning versus virtual learning is such a complicated topic,” says Dr. Bunyavanich. “For every family it’s going to require a different set of considerations about risk versus benefits and what their preferences are. Even though children are less susceptible overall, susceptibility might vary between individual children, and it’s still possible for children to carry the virus. You have to think of the whole web of complex interactions children have. That’s what makes it so hard.”