Silent Spreaders?

Children may play a larger role in community spread of COVID-19 than previously thought

By MGH NEWS AND PUBLIC AFFAIRS Research
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This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

In the most comprehensive study of COVID-19 pediatric patients to date, Harvard Medical School researchers based at Massachusetts General Hospital and Mass General Hospital for Children provide data showing that children may play a larger role in the community spread of COVID-19 than previously thought.

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The study, published in The Journal of Pediatrics, examined 192 children, adolescents and young adults who came to hospitals with symptoms of or suspected exposure to COVID-19. In this group, 49 individuals tested positive for SARS-CoV-2, the virus that causes COVID-19, and an additional 18 had a late-onset COVID-19-related illness.

The researchers found that infected children carried high levels of the virus, or viral load, in their respiratory secretions, even children with mild or no symptoms. Age did not affect the ability to carry a high viral load, which is associated with increased risk of transmitting the virus to others.

Notably, the team found that infected children in the asymptomatic or early infection phase had significantly higher viral loads than hospitalized adults with severe COVID-19.

The results carry implications for the reopening of schools, daycare centers and other facilities with a high density of children and close interaction with teachers and staff members, the authors said.

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“I was surprised by the high levels of virus we found in children of all ages, especially in the first two days of infection,” said lead study author Lael Yonker, HMS assistant professor of pediatrics at Mass General.

“I was not expecting the viral load to be so high,” said Yonker, who is co-director of the MGH Cystic Fibrosis Center. “You think of a hospital, and of all of the precautions taken to treat severely ill adults, but the viral loads of these hospitalized patients are significantly lower than a ‘healthy child’ who is walking around with a high SARS-CoV-2 viral load.”

In addition, the team found that although younger children had lower levels of ACE2—the receptor protein that SARS-CoV-2 targets to enter human cells—than older children and adults, this did not correlate with decreased viral load.

This suggests that children can carry a high viral load regardless of their susceptibility to developing COVID-19 infection, according to the authors.

“This study provides much-needed facts for policymakers to make the best decisions possible for schools, daycare centers and other institutions that serve children. Kids are a possible source of spreading this virus, and this should be taken into account in the planning stages for reopening schools.”

Alessio Fasano

Kids are not immune

The researchers note that although children with COVID-19 are not likely to become as seriously ill as adults, they can spread infection and bring the virus into their homes if they attend school as asymptomatic carriers or carriers with few symptoms.

Symptoms typical of COVID-19, such as fever, runny nose and cough, often overlap with other common childhood illnesses, including influenza and the common cold, which can confound an accurate diagnosis of COVID-19 in children, said Yonker.

This is a particular concern for families in certain socioeconomic groups, which have been harder hit in the pandemic, and for multigenerational families with vulnerable older adults in the same household. In the study, 51 percent of children with acute SARS-CoV-2 infection came from low-income communities compared to 2 percent from high-income communities.

“Kids are not immune from this infection, and their symptoms don’t correlate with exposure and infection,” said senior study author Alessio Fasano, HMS professor of pediatrics at Mass General.

“During this COVID-19 pandemic, we have mainly screened symptomatic subjects, so we have reached the erroneous conclusion that the vast majority of people infected are adults,” said Fasano, who is director of the Mucosal Immunology and Biology Research Center at Mass General. “However, our results show that kids are not protected against this virus. We should not discount children as potential spreaders for this virus.”

Contagion risk

In their study, the researchers measured viral load and antibody response in healthy children, children with acute SARS-CoV-2 infection and a smaller number of children with multisystem inflammatory syndrome in children (MIS-C), a multiorgan, systemic infection that can develop in children with COVID-19 several weeks after infection.

Study participants ranged from ages 0 to 22, with an average age of 10, and provided nose and throat swabs and blood samples to the Mass General Hospital for Children Pediatric COVID-19 Biorepository.

Along with viral load, the researchers examined expression of ACE2, a receptor protein found in epithelial tissue, such as the lining of the airway and lungs, which SARS-CoV-2 targets to enter human cells.

In another major finding from the study, the researchers challenged the current hypothesis that children are less likely to become infected or seriously ill because they have a lower number of ACE2 receptors.

Data from the study showed that lower numbers of ACE2 receptors in younger children did not correlate with decreased viral load, suggesting that children can remain contagious regardless of their susceptibility to COVID-19.

The researchers also studied immune response in MIS-C, which can include severe cardiac problems, shock and acute heart failure.

“This is a severe complication as a result of the immune response to COVID-19 infection, and the number of these patients is growing,” said Fasano. “And, as in adults with these very serious systemic complications, the heart seems to be the favorite organ targeted by post-COVID-19 immune response.”

Understanding MIS-C and post-infectious immune responses from pediatric COVID-19 patients is critical for developing next steps in treatment and prevention strategies, according to the researchers. Early insights into the immune dysfunction in MIS-C should prompt caution when developing vaccine strategies, noted Yonker.

Safe return

As Mass General Hospital for Children pediatricians, both Yonker and Fasano are constantly fielding questions from parents about the safe return of their children to school and daycare. They agree that the most critical question is what steps the schools will implement “to keep the kids, teachers and personnel safe.”

Recommendations from their study include not relying on body temperature or symptom monitoring to identify SARS-CoV-2 infection in the school setting.

The researchers emphasize infection-control measures, including social distancing, universal mask use when feasible, effective handwashing protocols and a combination of remote and in-person learning. They recommend routine and continued screening of all students for SARS-CoV-2 infection with timely reporting of the results an integral part of a safe return-to-school policy.

“This study provides much-needed facts for policymakers to make the best decisions possible for schools, daycare centers and other institutions that serve children,” said Fasano. “Kids are a possible source of spreading this virus, and this should be taken into account in the planning stages for reopening schools.”

A hurried return to school without proper planning could result in an uptick in COVID-19 infections, according to Fasano. “If schools were to reopen fully without necessary precautions, it is likely that children will play a larger role in this pandemic,” the authors conclude.

The research was supported by the National Heart, Lung, and Blood Institute, the Cystic Fibrosis Foundation, the National Institute of Child Health and Human Development, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the Centers for Disease Control and Prevention, the Mass General Department of Pediatrics, the Mass General Department of Obstetrics/Gynecology and private donors.

Adapted from a Mass General news release.