As schools reopen in parts of the United States, a paper published Thursday found that some children have significantly higher levels of virus in their airways than the most severely ill adults – suggesting their role in community spread may be larger than previously believed.

The study in The Journal of Pediatrics comes on the heels of two others that offer insights about children and COVID-19 transmission. On July 30, researchers reported in JAMA that children younger than 5 with mild or moderate illness have much higher levels of virus in the nose compared to older children and adults. Shortly before that, investigators in South Korea found in a household study that older children passed on the virus as readily as adults, while younger children did not.

All three studies were small and contradicted each other in some details so researchers said they could not draw any definitive conclusions based on any one of them alone. But taken together, they paint a worrisome new picture of children’s role in the pandemic.

Alessio Fasano, a physician at MassGeneral Hospital for Children and one of the new study’s authors, said that because children tend to exhibit mild symptoms or none at all, they were largely ignored in the early part of the outbreak and not tested. But they may have been acting as silent spreaders all along.

“Some people thought that children might be protected,” Fasano said. “This is incorrect. They may be as susceptible as adults – but just not visible.”

Lael Yonker, lead author and a pediatric specialist at Massachusetts General Hospital, expressed surprise that the viral loads of hospitalized adults who are usually kept isolated may be “significantly lower than a ‘healthy child’ who is walking around with a high SARS-CoV-2 viral load.”

Since the virus first appeared on Dec. 31, its impact on children has been among the most baffling. Time has confirmed that most children appear to have mild disease or no symptoms, but why that is remains a mystery.

The new paper provides one of the most detailed looks at the immune reaction in children, exposed to the coronavirus. Of the 192 pediatric patients seen at Boston’s Massachusetts General Hospital and Mass General Hospital for Children, 49 were diagnosed with acute infection and another 18 with MIS-C, the multi-inflammatory syndrome linked to the virus. The mean age of the children in the study was 10 years. The percentage of children who tested positive for the virus was about 25 percent, Fasano said, as compared with about 20 percent for adults.

Among the other preliminary findings: Age did not impact viral load (or amount of virus present) and that viral load appeared especially high about two days into the infection.

Another eye-opening finding involves immune receptors known as ACE2 that the virus uses to invade the body. Scientists had hypothesized that because children may have lower numbers of the receptors, they may be less likely to be infected or to transmit the virus. The data confirmed that younger children do have lower numbers of receptors than older childr

en and adults – but that this did not seem to be related to viral load.

A separate paper out this month from Children’s National Hospital in Washington, D.C. of 177 children and young adults with SARS-CoV-2 infections between March 15 and April 30 found that the youngest and oldest children were more likely to be hospitalized and the oldest were most likely to require critical care.

Roberta DeBiasi, an infectious-disease expert, and her co-authors noted that asthma was the most common underlying diagnosis in the children infected – but that they were not overrepresented in those who were hospitalized or critically ill.

“This suggests that although children and young adults with asthma may commonly experience exacerbation in response to SARS-CoV-2 infection, asthma exacerbation is not the primary determinant of more severe disease requiring hospitalization,” they wrote.

Bill Kapogiannis, a National Institutes of Health researcher in pediatric infectious diseases who was not involved in Fasano’s study, called those findings “potentially concerning” but said further investigation is needed to understand some of the signals.

“It’s interesting, but we need a bigger cohort to make strong conclusions,” he said.

Several such efforts are in the works. NIH has pledged as much as $20 million over four years to study biomarkers and other indicators that will characterize how the disease progresses in children and be able to predict severe illness in children.

“The central question is why is it that so many more children have milder illness compared to adults?” Kapogiannis said. “There is valuable information that we could learn and harness that could be used to treat this in all of us.”

Adrienne Randolph, a critical care specialist at Boston Children’s Hospital and a professor at Harvard Medical School, is leading a group involving 73 medical centers across the United States that is collecting records and biological samples from children. They are looking at numerous aspects of serious illness, such as the mix of antibodies present and how they change over time, and genetic sequencing of different types of patients.

Most importantly, Randolph said, “these teams are taking a deeper dive into trying to understand therapies and overcoming covid.”

So far most of the treatment regimens have been formulated on-the-fly through experimentation and word-of-mouth. But this work will hopefully be able to quantify the treatments and outcomes.

The most important lesson she said pediatric specialists have learned over the past eight months is that “this disease never stops surprising us.”

“I think we shouldn’t make any assumptions that minimize the virus,” Randolph said.

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